@article {pmid31622538, year = {2019}, author = {Zou, M and Jie, Z and Cui, B and Wang, H and Feng, Q and Zou, Y and Zhang, X and Yang, H and Wang, J and Zhang, F and Jia, H}, title = {Fecal microbiota transplantation results in bacterial strain displacement in patients with inflammatory bowel diseases.}, journal = {FEBS open bio}, volume = {}, number = {}, pages = {}, doi = {10.1002/2211-5463.12744}, pmid = {31622538}, issn = {2211-5463}, abstract = {Fecal microbiota transplantation (FMT), which is thought to have the potential to correct dysbiosis of gut microbiota, has been used to treat inflammatory bowel disease (IBD) for almost a decade. Here, we report an interventional prospective cohort study performed to elucidate the extent of and processes underlying microbiota engraftment in IBD patients after FMT treatment. The cohort included two categories of patients: (1) patients with moderate to severe Crohn's disease (CD)（Harvey-Bradshaw Index ≥ 7, n = 11） and (2) patients with ulcerative colitis (UC) (Montreal classification S2 and S3, n = 4). All patients were treated with a single FMT (via mid-gut, from healthy donors) and follow-up visits were performed at baseline, 3 days, one week, and one month after FMT (missing time points included). At each follow-up time point, fecal samples and clinical metadata were collected. For comparative analysis, 10 fecal samples from 10 healthy donors were included to represent the diversity level of normal gut microbiota. Additionally, the metagenomic data of 25 fecal samples from 5 individuals with metabolic syndrome who underwent autologous FMT treatment were downloaded from a previous published paper to represent fluctuations in microbiota induced during FMT. All fecal samples underwent shotgun metagenomic sequencing. We found that 3 days after FMT, 11 out of 15 recipients were in remission (3 out of 4 UC recipients; 8 out of 11 CD recipients). Generally, bacterial colonization was observed to be lower in CD recipients than in UC recipients at both species and strain levels. Furthermore, across species, different strains displayed disease-specific displacement advantages under two-disease status. Finally, most post-FMT species (> 80%) could be properly predicted (AUC > 85%) using a random forest classification model, with the gut microbiota composition and clinical parameters of pre-FMT recipients acting as factors that contribute to prediction accuracy.}, }
@article {pmid31617360, year = {2019}, author = {Lam, KL and Cheung, PCK}, title = {Carbohydrate-based Prebiotics in Targeted Modulation of Gut Microbiome.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.9b04811}, pmid = {31617360}, issn = {1520-5118}, abstract = {The Human Microbiome Project has prompted unprecedented advancement to microbiome science. Personalized microbiome modulation with precision (PMMP) is one of the emerging yet challenging field in future microbiome research. Carbohydrate-based prebiotics (CBPs) have been shown to modulate gut microbiome in various extents by their different structural characteristics such as degree of polymerization, branching, glycosidic linkage, monosaccharide profile, and chemical modification. Subsequently, a targeted modulation of microbiome might be achieved by using CBPs with specific structure. A multi-dimensional database can be established based on the structure-microbiome (SMR) and structure-microbial-marker (SMMR) relationships. Such relationships could facilitate the development of synbiotics and PMMP.}, }
@article {pmid31617205, year = {2019}, author = {Sharma, A and Das, P and Buschmann, M and Gilbert, JA}, title = {The future of microbiome-based therapeutics in clinical applications.}, journal = {Clinical pharmacology and therapeutics}, volume = {}, number = {}, pages = {}, doi = {10.1002/cpt.1677}, pmid = {31617205}, issn = {1532-6535}, abstract = {The microbiome, a collection of microorganisms, their genomes, and the surrounding environmental conditions, is akin to a human organ, and knowledge is emerging on its role in human health and diseases. The influence of the microbiome in drug response has only been investigated in detail for the last 10 years. The human microbiome is a complex and highly dynamic system, which varies dramatically between individuals, yet there exists a common core microbiome that is heritable and can be transmitted to progeny. Here, we review the role of the human microbiome, which is now widely accepted as a major factor that drives the interpersonal variation in therapeutic response. We describe examples in which the microbiome modifies drug action. Despite its complexity, the microbiome can be readily altered, with the potential to increase the benefits and reduce the toxicity and side-effects associated with pharmaceutical drugs. The potential of new microbiome-based strategies, such as Fecal Microbiota Transplant (FMT), probiotics and phage therapy as promising medical therapeutics are outlined. We also suggest a combination reductionist and system-level approaches that could be applied to further investigate the role of microbiota in drug metabolism modulation of drug response. Finally, we emphasize the importance of combining microbiome and pharmacology studies, as a novel means to treat disease and reduce side effects.}, }
@article {pmid31616466, year = {2019}, author = {Srivastava, D and Baksi, KD and Kuntal, BK and Mande, SS}, title = {"EviMass": A Literature Evidence-Based Miner for Human Microbial Associations.}, journal = {Frontiers in genetics}, volume = {10}, number = {}, pages = {849}, doi = {10.3389/fgene.2019.00849}, pmid = {31616466}, issn = {1664-8021}, abstract = {The importance of understanding microbe-microbe as well as microbe-disease associations is one of the key thrust areas in human microbiome research. High-throughput metagenomic and transcriptomic projects have fueled discovery of a number of new microbial associations. Consequently, a plethora of information is being added routinely to biomedical literature, thereby contributing toward enhancing our knowledge on microbial associations. In this communication, we present a tool called "EviMass" (Evidence based mining of human Microbial Associations), which can assist biologists to validate their predicted hypotheses from new microbiome studies. Users can interactively query the processed back-end database for microbe-microbe and disease-microbe associations. The EviMass tool can also be used to upload microbial association networks generated from a human "disease-control" microbiome study and validate the associations from biomedical literature. Additionally, a list of differentially abundant microbes for the corresponding disease can be queried in the tool for reported evidences. The results are presented as graphical plots, tabulated summary, and other evidence statistics. EviMass is a comprehensive platform and is expected to enable microbiome researchers not only in mining microbial associations, but also enriching a new research hypothesis. The tool is available free for academic use at https://web.rniapps.net/evimass.}, }
@article {pmid31608855, year = {2019}, author = {Lilley, ECH and Morris, AT and Silberg, JL}, title = {The Mid-Atlantic Twin Registry of Virginia Commonwealth University.}, journal = {Twin research and human genetics : the official journal of the International Society for Twin Studies}, volume = {}, number = {}, pages = {1-4}, doi = {10.1017/thg.2019.87}, pmid = {31608855}, issn = {1832-4274}, abstract = {The Mid-Atlantic Twin Registry (MATR) is a population-based registry of more than 60,000 twins primarily born or living in Virginia, North Carolina and South Carolina. Researchers may utilize the MATR for administration of research services, including study recruitment, data or sample (e.g., DNA) collection, archival dataset creation, as well as data collection through mailed, phone or online surveys. In addition, the MATR houses the MATR Repository, with over 1700 DNA samples primarily from whole blood available for researchers interested in DNA genotyping. For over 40 years MATR twins have participated in research studies with investigators from a range of scientific disciplines and institutions. These studies, which have resulted in numerous publications, explored diverse topics, including substance use, smoking behaviors, developmental psychopathology, bullying, children's health, cardiovascular disease, cancer, the human microbiome, epigenetics of aging, children of twins and sleep homeostasis. Researchers interested in utilizing twins are encouraged to contact the MATR to discuss potential research opportunities.}, }
@article {pmid31608406, year = {2019}, author = {Farmakiotis, D}, title = {The human microbiome and checkpoint inhibition: potential benefits from antibiotic stewardship.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {}, number = {}, pages = {}, doi = {10.1093/cid/ciz1003}, pmid = {31608406}, issn = {1537-6591}, }
@article {pmid31608279, year = {2019}, author = {Kang, W and Jia, Z and Tang, D and Zhao, X and Shi, J and Jia, Q and He, K and Feng, Q}, title = {Time-Course Transcriptome Analysis for Drug Repositioning in Fusobacterium nucleatum-Infected Human Gingival Fibroblasts.}, journal = {Frontiers in cell and developmental biology}, volume = {7}, number = {}, pages = {204}, doi = {10.3389/fcell.2019.00204}, pmid = {31608279}, issn = {2296-634X}, abstract = {Fusobacterium nucleatum (F. nucleatum) is a crucial periodontal pathogen and human gingival fibroblasts (GFs) are the first line of defense against oral pathogens. However, the research on potential molecular mechanisms of host defense and effective treatment of F. nucleatum infection in GFs remains scarce. In this study, we undertook a time-series experiment and performed an RNA-seq analysis to explore gene expression profiles during the process of F. nucleatum infection in GFs. Differentially expressed genes (DEGs) could be divided into three coexpression clusters. Functional analysis revealed that the immune-related signaling pathways were more overrepresented at the early stage, while metabolic pathways were mainly enriched at the late stage. We computationally identified several U.S. Food and Drug Administration (FDA)-approved drugs that could protect the F. nucleatum infected GFs via a coexpression-based drug repositioning approach. Biologically, we confirmed that six drugs (etravirine, zalcitabine, wortmannin, calcium D-pantothenate, ellipticine, and tanespimycin) could significantly decrease F. nucleatum-induced reactive oxygen species (ROS) generation and block the Protein Kinase B (PKB/AKT)/mitogen-activated protein kinase signaling pathways. Our study provides more detailed molecular mechanisms of the process by which F. nucleatum infects GFs and illustrates the value of the cogena-based drug repositioning method and the potential therapeutic application of these tested drugs in the treatment of F. nucleatum infection.}, }
@article {pmid31607556, year = {2019}, author = {Tett, A and Huang, KD and Asnicar, F and Fehlner-Peach, H and Pasolli, E and Karcher, N and Armanini, F and Manghi, P and Bonham, K and Zolfo, M and De Filippis, F and Magnabosco, C and Bonneau, R and Lusingu, J and Amuasi, J and Reinhard, K and Rattei, T and Boulund, F and Engstrand, L and Zink, A and Collado, MC and Littman, DR and Eibach, D and Ercolini, D and Rota-Stabelli, O and Huttenhower, C and Maixner, F and Segata, N}, title = {The Prevotella copri Complex Comprises Four Distinct Clades Underrepresented in Westernized Populations.}, journal = {Cell host & microbe}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.chom.2019.08.018}, pmid = {31607556}, issn = {1934-6069}, abstract = {Prevotella copri is a common human gut microbe that has been both positively and negatively associated with host health. In a cross-continent meta-analysis exploiting >6,500 metagenomes, we obtained >1,000 genomes and explored the genetic and population structure of P. copri. P. copri encompasses four distinct clades (>10% inter-clade genetic divergence) that we propose constitute the P. copri complex, and all clades were confirmed by isolate sequencing. These clades are nearly ubiquitous and co-present in non-Westernized populations. Genomic analysis showed substantial functional diversity in the complex with notable differences in carbohydrate metabolism, suggesting that multi-generational dietary modifications may be driving reduced prevalence in Westernized populations. Analysis of ancient metagenomes highlighted patterns of P. copri presence consistent with modern non-Westernized populations and a clade delineation time pre-dating human migratory waves out of Africa. These findings reveal that P. copri exhibits a high diversity that is underrepresented in Western-lifestyle populations.}, }
@article {pmid31603985, year = {2019}, author = {McCrory, C and Fiorito, G and McLoughlin, S and Polidoro, S and Ni Cheallaigh, C and Bourke, N and Karisola, P and Alenius, H and Vineis, P and Layte, R and Kenny, RA}, title = {Epigenetic clocks and allostatic load reveal potential sex-specific drivers of biological ageing.}, journal = {The journals of gerontology. Series A, Biological sciences and medical sciences}, volume = {}, number = {}, pages = {}, doi = {10.1093/gerona/glz241}, pmid = {31603985}, issn = {1758-535X}, abstract = {Allostatic Load (AL) and epigenetic clocks both attempt to characterise the accelerated ageing of biological systems, but at present it is unclear whether these measures are complementary or distinct. This study examines the cross-sectional association of AL with Epigenetic Age Acceleration (EAA) in a sub-sample of 490 community dwelling older-adults participating in The Irish Longitudinal study on Aging (TILDA). A battery of 14 biomarkers representing the activity of 4 different physiological systems: immunological, cardiovascular, metabolic, renal, was used to construct the AL score. DNA methylation age was computed according to the algorithms described by Horvath, Hannum and Levine allowing for estimation of whether an individual is experiencing accelerated or decelerated ageing. Horvath, Hannum and Levine EAA correlated 0.05, 0.03, and 0.21 with AL respectively. Disaggregation by sex revealed that AL was more strongly associated with EAA in men compared with women as assessed using Horvath's clock. Metabolic dysregulation was a strong driver of EAA in men as assessed using Horvath and Levine's clock, while metabolic and cardiovascular dysregulation were associated with EAA in women using Levine's clock. Results indicate that AL and the epigenetic clocks are measuring different age-related variance and implicate sex-specific drivers of biological ageing.}, }
@article {pmid31601287, year = {2019}, author = {Stinson, LF}, title = {Establishment of the early-life microbiome: a DOHaD perspective.}, journal = {Journal of developmental origins of health and disease}, volume = {}, number = {}, pages = {1-10}, doi = {10.1017/S2040174419000588}, pmid = {31601287}, issn = {2040-1752}, abstract = {The human microbiome plays a number of critical roles in host physiology. Evidence from longitudinal cohort studies and animal models strongly supports the theory that maldevelopment of the microbiome in early life can programme later-life disease. The early-life microbiome develops in a clear stepwise manner over the first 3 years of life. During this highly dynamic time, insults such as antibiotic use and formula feeding can adversely affect the composition and temporal development of the microbiome. Such experiences predispose infants for the development of chronic health conditions later in life. This review highlights key factors that disrupt the early-life microbiome and highlights major non-communicable diseases which are underpinned by early-life dysbiosis.}, }
@article {pmid31600503, year = {2019}, author = {Shkoporov, AN and Clooney, AG and Sutton, TDS and Ryan, FJ and Daly, KM and Nolan, JA and McDonnell, SA and Khokhlova, EV and Draper, LA and Forde, A and Guerin, E and Velayudhan, V and Ross, RP and Hill, C}, title = {The Human Gut Virome Is Highly Diverse, Stable, and Individual Specific.}, journal = {Cell host & microbe}, volume = {26}, number = {4}, pages = {527-541.e5}, doi = {10.1016/j.chom.2019.09.009}, pmid = {31600503}, issn = {1934-6069}, abstract = {The human gut contains a vast array of viruses, mostly bacteriophages. The majority remain uncharacterized, and their roles in shaping the gut microbiome and in impacting on human health remain poorly understood. We performed longitudinal metagenomic analysis of fecal viruses in healthy adults that reveal high temporal stability, individual specificity, and correlation with the bacterial microbiome. Using a database-independent approach that uses most of the sequencing data, we uncovered the existence of a stable, numerically predominant individual-specific persistent personal virome. Clustering of viral genomes and de novo taxonomic annotation identified several groups of crAss-like and Microviridae bacteriophages as the most stable colonizers of the human gut. CRISPR-based host prediction highlighted connections between these stable viral communities and highly predominant gut bacterial taxa such as Bacteroides, Prevotella, and Faecalibacterium. This study provides insights into the structure of the human gut virome and serves as an important baseline for hypothesis-driven research.}, }
@article {pmid31600337, year = {2019}, author = {Andreev, VP and Liu, G and Zee, J and Henn, L and Flores, GE and Merion, RM}, title = {Clustering of the structures by using "snakes-&-dragons" approach, or correlation matrix as a signal.}, journal = {PloS one}, volume = {14}, number = {10}, pages = {e0223267}, doi = {10.1371/journal.pone.0223267}, pmid = {31600337}, issn = {1932-6203}, abstract = {Biological, ecological, social, and technological systems are complex structures with multiple interacting parts, often represented by networks. Correlation matrices describing interdependency of the variables in such structures provide key information for comparison and classification of such systems. Classification based on correlation matrices could supplement or improve classification based on variable values, since the former reveals similarities in system structures, while the latter relies on the similarities in system states. Importantly, this approach of clustering correlation matrices is different from clustering elements of the correlation matrices, because our goal is to compare and cluster multiple networks-not the nodes within the networks. A novel approach for clustering correlation matrices, named "snakes-&-dragons," is introduced and illustrated by examples from neuroscience, human microbiome, and macroeconomics.}, }
@article {pmid31597320, year = {2019}, author = {Holster, S and Hooiveld, GJ and Repsilber, D and Vos, WM and Brummer, RJ and König, J}, title = {Allogenic Faecal Microbiota Transfer Induces Immune-Related Gene Sets in the Colon Mucosa of Patients with Irritable Bowel Syndrome.}, journal = {Biomolecules}, volume = {9}, number = {10}, pages = {}, doi = {10.3390/biom9100586}, pmid = {31597320}, issn = {2218-273X}, support = {Spinoza 2018//Nederlands Organisatie voor Wetenschappelijk Onderzoek (NWO)/ ; ESPEN Research Fellowship 2017//European Society for Clinical Nutrition and Metabolism/ ; 20110225//Knowledge Foundation/ ; }, abstract = {Faecal microbiota transfer (FMT) consists of the introduction of new microbial communities into the intestine of a patient, with the aim of restoring a disturbed gut microbiota. Even though it is used as a potential treatment for various diseases, it is unknown how the host mucosa responds to FMT. This study aims to investigate the colonic mucosa gene expression response to allogenic (from a donor) or autologous (own) FMT in patients with irritable bowel syndrome (IBS). In a recently conducted randomised, double-blinded, controlled clinical study, 17 IBS patients were treated with FMT by colonoscopy. RNA was isolated from colonic biopsies collected by sigmoidoscopy at baseline, as well as two weeks and eight weeks after FMT. In patients treated with allogenic FMT, predominantly immune response-related gene sets were induced, with the strongest response two weeks after the FMT. In patients treated with autologous FMT, predominantly metabolism-related gene sets were affected. Furthermore, several microbiota genera showed correlations with immune-related gene sets, with different correlations found after allogenic compared to autologous FMT. This study shows that the microbe-host response is influenced by FMT on the mucosal gene expression level, and that there are clear differences in response to allogenic compared to autologous FMT.}, }
@article {pmid31594829, year = {2019}, author = {Zhao, H and Fu, S and Yu, Y and Zhang, Z and Li, P and Ma, Q and Jia, W and Ning, K and Qu, S and Liu, Q}, title = {MetaMed: Linking Microbiota Functions with Medicine Therapeutics.}, journal = {mSystems}, volume = {4}, number = {5}, pages = {}, doi = {10.1128/mSystems.00413-19}, pmid = {31594829}, issn = {2379-5077}, abstract = {Understanding how the human microbiome affects human health has consequences for treating disease and minimizing unwanted side effects in clinical research. Here, we present MetaMed (http://metamed.rwebox.com/index), a novel and integrative system-wide correlation mapping system to link bacterial functions and medicine therapeutics, providing novel hypotheses for deep investigation of microbe therapeutic effects on human health. Furthermore, comprehensive relationships between microbes living in the environment and drugs were discovered, providing a rich source for discovering microbiota metabolites with great potential for pharmaceutical applications.}, }
@article {pmid31592582, year = {2019}, author = {Li, W and Ma, ZS}, title = {Diversity scaling of human vaginal microbial communities.}, journal = {Zoological research}, volume = {}, number = {}, pages = {}, doi = {10.24272/j.issn.2095-8137.2019.068}, pmid = {31592582}, issn = {2095-8137}, abstract = {The composition and diversity of the human vaginal microbial community have been investigated intensively due to the diversity-stability relationship (DSR)-based hypothesis for bacterial vaginosis (BV) etiology, which was first proposed in the 1990s and has received renewed interest in recent years. Nevertheless, diversity changes (scaling) across individuals in a cohort or population have not yet been addressed, which is significant both theoretically and practically. Theoretically, biodiversity scaling is the core of biogeography, and practically, inter-subject heterogeneity is critical for understanding the etiology and epidemiology of human microbiome-associated diseases such as BV. Here we applied the diversity-area relationship (DAR), a recent extension to the classic species-area relationship (SAR), to study diversity scaling of the vaginal microbiome by reanalyzing reported data collected from 1 107 postpartum women. The model used here characterized the power-law (or its extension) relationships between accrued diversity and areas (numbers of individuals), upon which four biogeographic profiles were thus defined. Specifically, we established the DAR profile (relationship between diversity scaling parameter and so-termed diversity order (q)), similarly pair-wise diversity overlap (PDO) profile, maximal accrual diversity (MAD) profile, and ratio of individual-level to population-level diversity (RIP) profile. These four profiles offer valuable tools to assess and predict diversity scaling (changes) in the human vaginal microbiome across individuals, as well as to understand the dynamics of vaginal microbiomes in healthy women.}, }
@article {pmid31590679, year = {2019}, author = {Amato, KR and Mallott, EK and McDonald, D and Dominy, NJ and Goldberg, T and Lambert, JE and Swedell, L and Metcalf, JL and Gomez, A and Britton, GAO and Stumpf, RM and Leigh, SR and Knight, R}, title = {Convergence of human and Old World monkey gut microbiomes demonstrates the importance of human ecology over phylogeny.}, journal = {Genome biology}, volume = {20}, number = {1}, pages = {201}, doi = {10.1186/s13059-019-1807-z}, pmid = {31590679}, issn = {1474-760X}, abstract = {BACKGROUND: Comparative data from non-human primates provide insight into the processes that shaped the evolution of the human gut microbiome and highlight microbiome traits that differentiate humans from other primates. Here, in an effort to improve our understanding of the human microbiome, we compare gut microbiome composition and functional potential in 14 populations of humans from ten nations and 18 species of wild, non-human primates.<br><br>RESULTS: Contrary to expectations from host phylogenetics, we find that human gut microbiome composition and functional potential are more similar to those of cercopithecines, a subfamily of Old World monkey, particularly baboons, than to those of African apes. Additionally, our data reveal more inter-individual variation in gut microbiome functional potential within the human species than across other primate species, suggesting that the human gut microbiome may exhibit more plasticity in response to environmental variation compared to that of other primates.<br><br>CONCLUSIONS: Given similarities of ancestral human habitats and dietary strategies to those of baboons, these findings suggest that convergent ecologies shaped the gut microbiomes of both humans and cercopithecines, perhaps through environmental exposure to microbes, diet, and/or associated physiological adaptations. Increased inter-individual variation in the human microbiome may be associated with human dietary diversity or the ability of humans to inhabit novel environments. Overall, these findings show that diet, ecology, and physiological adaptations are more important than host-microbe co-diversification in shaping the human microbiome, providing a key foundation for comparative analyses of the role of the microbiome in human biology and health.}, }
@article {pmid31588499, year = {2019}, author = {Bradley, PH and Pollard, KS}, title = {phylogenize: correcting for phylogeny reveals genes associated with microbial distributions.}, journal = {Bioinformatics (Oxford, England)}, volume = {}, number = {}, pages = {}, doi = {10.1093/bioinformatics/btz722}, pmid = {31588499}, issn = {1367-4811}, abstract = {SUMMARY: Phylogenetic comparative methods are powerful but presently under-utilized ways to identify microbial genes underlying differences in community composition. These methods help to identify functionally important genes because they test for associations beyond those expected when related microbes occupy similar environments. We present phylogenize, a pipeline with web, QIIME 2, and R interfaces that allows researchers to perform phylogenetic regression on 16S amplicon and shotgun sequencing data and to visualize results. phylogenize applies broadly to both host-associated and environmental microbiomes. Using Human Microbiome Project and Earth Microbiome Project data, we show that phylogenize draws similar conclusions from 16S versus shotgun sequencing and reveals both known and candidate pathways associated with host colonization.<br><br>AVAILABILITY: phylogenize is available at https://phylogenize.org and https://bitbucket.org/pbradz/phylogenize.}, }
@article {pmid31583780, year = {2019}, author = {Hooks, KB and O'Malley, MA}, title = {Contrasting Strategies: Human Eukaryotic versus Bacterial Microbiome Research.}, journal = {The Journal of eukaryotic microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1111/jeu.12766}, pmid = {31583780}, issn = {1550-7408}, abstract = {Most discussions of human microbiome research have focused on bacterial investigations and findings. Our target is to understand how human eukaryotic microbiome research is developing, its potential distinctiveness, and how problems can be addressed. We start with an overview of the entire eukaryotic microbiome literature (578 papers), show tendencies in the human-based microbiome literature, then compare the eukaryotic field to more developed human bacterial microbiome research. We are particularly concerned with problems of interpretation that are already apparent in human bacterial microbiome research (e.g., disease causality, probiotic interventions, evolutionary claims). We show where each field converges and diverges, and what this might mean for progress in human eukaryotic microbiome research. Our analysis then makes constructive suggestions for the future of the field.}, }
@article {pmid31582523, year = {2019}, author = {Sugimoto, Y and Camacho, FR and Wang, S and Chankhamjon, P and Odabas, A and Biswas, A and Jeffrey, PD and Donia, MS}, title = {A metagenomic strategy for harnessing the chemical repertoire of the human microbiome.}, journal = {Science (New York, N.Y.)}, volume = {}, number = {}, pages = {}, doi = {10.1126/science.aax9176}, pmid = {31582523}, issn = {1095-9203}, abstract = {Remarkable progress has been made in determining the effects of the microbiome on human physiology and disease, but the underlying molecules and mechanisms governing these effects remain largely unexplored. Here, we combine a new computational algorithm with synthetic biology to access biologically active small molecules encoded directly in human microbiome-derived metagenomic sequencing data. We discover that members of a clinically used class of molecules are widely encoded in the human microbiome, and that they exert potent antibacterial activities against neighboring microbes, implying a possible role in niche competition and host defense. Our approach paves the way toward a systematic unveiling of the chemical repertoire encoded by the human microbiome and provides a generalizable platform for discovering molecular mediators of microbiome-host and microbiome-microbiome interactions.}, }
@article {pmid31575764, year = {2019}, author = {Chmiel, JA and Daisley, BA and Burton, JP and Reid, G}, title = {Deleterious Effects of Neonicotinoid Pesticides on Drosophila melanogaster Immune Pathways.}, journal = {mBio}, volume = {10}, number = {5}, pages = {}, doi = {10.1128/mBio.01395-19}, pmid = {31575764}, issn = {2150-7511}, abstract = {Neonicotinoid insecticides are common agrochemicals that are used to kill pest insects and improve crop yield. However, sublethal exposure can exert unintentional toxicity to honey bees and other beneficial pollinators by dysregulating innate immunity. Generation of hydrogen peroxide (H2O2) by the dual oxidase (Duox) pathway is a critical component of the innate immune response, which functions to impede infection and maintain homeostatic regulation of the gut microbiota. Despite the importance of this pathway in gut immunity, the consequences of neonicotinoid exposure on Duox signaling have yet to be studied. Here, we use a Drosophila melanogaster model to investigate the hypothesis that imidacloprid (a common neonicotinoid) can affect the Duox pathway. The results demonstrated that exposure to sublethal imidacloprid reduced H2O2 production by inhibiting transcription of the Duox gene. Furthermore, the reduction in Duox expression was found to be a result of imidacloprid interacting with the midgut portion of the immune deficiency pathway. This impairment led to a loss of microbial regulation, as exemplified by a compositional shift and increased total abundance of Lactobacillus and Acetobacter spp. (dominant microbiota members) found in the gut. In addition, we demonstrated that certain probiotic lactobacilli could ameliorate Duox pathway impairment caused by imidacloprid, but this effect was not directly dependent on the Duox pathway itself. This study is the first to demonstrate the deleterious effects that neonicotinoids can have on Duox-mediated generation of H2O2 and highlights a novel coordination between two important innate immune pathways present in insects.IMPORTANCE Sublethal exposure to certain pesticides (e.g., neonicotinoid insecticides) is suspected to contribute to honey bee (Apis mellifera) population decline in North America. Neonicotinoids are known to interfere with immune pathways in the gut of insects, but the underlying mechanisms remain elusive. We used a Drosophila melanogaster model to understand how imidacloprid (a common neonicotinoid) interferes with two innate immune pathways-Duox and Imd. We found that imidacloprid dysregulates these pathways to reduce hydrogen peroxide production, ultimately leading to a dysbiotic shift in the gut microbiota. Intriguingly, we found that presupplementation with probiotic bacteria could mitigate the harmful effects of imidacloprid. Thus, these observations uncover a novel mechanism of pesticide-induced immunosuppression that exploits the interconnectedness of two important insect immune pathways.}, }
@article {pmid31572693, year = {2019}, author = {Reid, G}, title = {The Need to Focus on Therapy Instead of Associations.}, journal = {Frontiers in cellular and infection microbiology}, volume = {9}, number = {}, pages = {327}, doi = {10.3389/fcimb.2019.00327}, pmid = {31572693}, issn = {2235-2988}, abstract = {Molecular analyses of the vaginal microbiota have uncovered a vast array of organisms in this niche, but not so far changed what has been known for a long time: lactobacilli are dominant in health, and the diagnosis and treatment of symptomatic bacterial vaginosis is sub-optimal, and has not changed for over 40 years. While the lowering cost of DNA sequencing has attracted more researchers to the field, and bioinformatics, and statistical tools have made it possible to produce large datasets, it is functional and actionable studies that are more urgently needed, not more microbial abundance, and health or disease-associative data. The triggers of dysbiosis remain to be identified, but ultimately treatment will require disrupting biofilms of primarily anaerobic bacteria and replacing them with the host's own lactobacilli, or health-promoting organisms. The options of using probiotic strains to displace the biofilms and for prebiotics to encourage resurgence of the indigenous lactobacilli hold great promise, but more researchers need to develop, and test these concepts in humans. The enormity of the problem of vaginal dysbiosis cannot be understated. It should not take another 40 years to offer better management options.}, }
@article {pmid31563878, year = {2019}, author = {Cammarota, G and Ianiro, G and Kelly, CR and Mullish, BH and Allegretti, JR and Kassam, Z and Putignani, L and Fischer, M and Keller, JJ and Costello, SP and Sokol, H and Kump, P and Satokari, R and Kahn, SA and Kao, D and Arkkila, P and Kuijper, EJ and Vehreschild, MJG and Pintus, C and Lopetuso, L and Masucci, L and Scaldaferri, F and Terveer, EM and Nieuwdorp, M and López-Sanromán, A and Kupcinskas, J and Hart, A and Tilg, H and Gasbarrini, A}, title = {International consensus conference on stool banking for faecal microbiota transplantation in clinical practice.}, journal = {Gut}, volume = {}, number = {}, pages = {}, doi = {10.1136/gutjnl-2019-319548}, pmid = {31563878}, issn = {1468-3288}, abstract = {Although faecal microbiota transplantation (FMT) has a well-established role in the treatment of recurrent Clostridioides difficile infection (CDI), its widespread dissemination is limited by several obstacles, including lack of dedicated centres, difficulties with donor recruitment and complexities related to regulation and safety monitoring. Given the considerable burden of CDI on global healthcare systems, FMT should be widely available to most centres.Stool banks may guarantee reliable, timely and equitable access to FMT for patients and a traceable workflow that ensures safety and quality of procedures. In this consensus project, FMT experts from Europe, North America and Australia gathered and released statements on the following issues related to the stool banking: general principles, objectives and organisation of the stool bank; selection and screening of donors; collection, preparation and storage of faeces; services and clients; registries, monitoring of outcomes and ethical issues; and the evolving role of FMT in clinical practice,Consensus on each statement was achieved through a Delphi process and then in a plenary face-to-face meeting. For each key issue, the best available evidence was assessed, with the aim of providing guidance for the development of stool banks in order to promote accessibility to FMT in clinical practice.}, }
@article {pmid31555247, year = {2019}, author = {Ghose, C and Ly, M and Schwanemann, LK and Shin, JH and Atab, K and Barr, JJ and Little, M and Schooley, RT and Chopyk, J and Pride, DT}, title = {The Virome of Cerebrospinal Fluid: Viruses Where We Once Thought There Were None.}, journal = {Frontiers in microbiology}, volume = {10}, number = {}, pages = {2061}, doi = {10.3389/fmicb.2019.02061}, pmid = {31555247}, issn = {1664-302X}, abstract = {Traditionally, medicine has held that some human body sites are sterile and that the introduction of microbes to these sites results in infections. This paradigm shifted significantly with the discovery of the human microbiome and acceptance of these commensal microbes living across the body. However, the central nervous system (CNS) is still believed by many to be sterile in healthy people. Using culture-independent methods, we examined the virome of cerebrospinal fluid (CSF) from a cohort of mostly healthy human subjects. We identified a community of DNA viruses, most of which were identified as bacteriophages. Compared to other human specimen types, CSF viromes were not ecologically distinct. There was a high alpha diversity cluster that included feces, saliva, and urine, and a low alpha diversity cluster that included CSF, body fluids, plasma, and breast milk. The high diversity cluster included specimens known to have many bacteria, while other specimens traditionally assumed to be sterile formed the low diversity cluster. There was an abundance of viruses shared among CSF, breast milk, plasma, and body fluids, while each generally shared less with urine, feces, and saliva. These shared viruses ranged across different virus families, indicating that similarities between these viromes represent more than just a single shared virus family. By identifying a virome in the CSF of mostly healthy individuals, it is now less likely that any human body site is devoid of microbes, which further highlights the need to decipher the role that viral communities may play in human health.}, }
@article {pmid31555238, year = {2019}, author = {Pires, ES and Hardoim, CCP and Miranda, KR and Secco, DA and Lobo, LA and de Carvalho, DP and Han, J and Borchers, CH and Ferreira, RBR and Salles, JF and Domingues, RMCP and Antunes, LCM}, title = {The Gut Microbiome and Metabolome of Two Riparian Communities in the Amazon.}, journal = {Frontiers in microbiology}, volume = {10}, number = {}, pages = {2003}, doi = {10.3389/fmicb.2019.02003}, pmid = {31555238}, issn = {1664-302X}, abstract = {During the last decades it has become increasingly clear that the microbes that live on and in humans are critical for health. The communities they form, termed microbiomes, are involved in fundamental processes such as the maturation and constant regulation of the immune system. Additionally, they constitute a strong defense barrier to invading pathogens, and are also intricately linked to nutrition. The parameters that affect the establishment and maintenance of these microbial communities are diverse, and include the genetic background, mode of birth, nutrition, hygiene, and host lifestyle in general. Here, we describe the characterization of the gut microbiome of individuals living in the Amazon, and the comparison of these microbial communities to those found in individuals from an urban, industrialized setting. Our results showed striking differences in microbial communities from these two types of populations. Additionally, we used high-throughput metabolomics to study the chemical ecology of the gut environment and found significant metabolic changes between the two populations. Although we cannot point out a single cause for the microbial and metabolic changes observed between Amazonian and urban individuals, they are likely to include dietary differences as well as diverse patterns of environmental exposure. To our knowledge, this is the first description of gut microbial and metabolic profiles in Amazonian populations, and it provides a starting point for thorough characterizations of the impact of individual environmental conditions on the human microbiome and metabolome.}, }
@article {pmid31546582, year = {2019}, author = {Dizzell, S and Nazli, A and Reid, G and Kaushic, C}, title = {Protective Effect of Probiotic Bacteria and Estrogen in Preventing HIV-1-Mediated Impairment of Epithelial Barrier Integrity in Female Genital Tract.}, journal = {Cells}, volume = {8}, number = {10}, pages = {}, doi = {10.3390/cells8101120}, pmid = {31546582}, issn = {2073-4409}, support = {FRN 126019/CAPMC/CIHR/Canada ; FRN 138657/CAPMC/CIHR/Canada ; AHRC 779//Ontario HIV Treatment Network/ ; }, abstract = {Approximately 40% of global HIV-1 transmission occurs in the female genital tract (FGT) through heterosexual transmission. Epithelial cells lining the FGT provide the first barrier to HIV-1 entry. Previous studies have suggested that certain hormonal contraceptives or a dysbiosis of the vaginal microbiota can enhance HIV-1 acquisition in the FGT. We examined the effects of lactobacilli and female sex hormones on the barrier functions and innate immune responses of primary endometrial genital epithelial cells (GECs). Two probiotic strains, Lactobacillus reuteri RC-14 and L. rhamnosus GR-1, were tested, as were sex hormones estrogen (E2), progesterone (P4), and the hormonal contraceptive medroxyprogesterone acetate (MPA). Our results demonstrate that probiotic lactobacilli enhance barrier function without affecting cytokines. Treatment of GECs with MPA resulted in reduced barrier function. In contrast, E2 treatment enhanced barrier function and reduced production of proinflammatory cytokines. Comparison of hormones plus lactobacilli as a pre-treatment prior to HIV exposure revealed a dominant effect of lactobacilli in preventing loss of barrier function by GECs. In summary, the combination of E2 and lactobacilli had the best protective effect against HIV-1 seen by enhancement of barrier function and reduction in proinflammatory cytokines. These studies provide insights into how probiotic lactobacilli in the female genital microenvironment can alter HIV-1-mediated barrier disruption and how the combination of E2 and lactobacilli may decrease susceptibility to primary HIV infection.}, }
@article {pmid31545899, year = {2019}, author = {Chu, J and Vila-Farres, X and Brady, SF}, title = {Bioactive syn-BNP cyclic peptides inspired by nonribosomal peptide synthetase gene clusters from the human microbiome.}, journal = {Journal of the American Chemical Society}, volume = {}, number = {}, pages = {}, doi = {10.1021/jacs.9b07317}, pmid = {31545899}, issn = {1520-5126}, abstract = {Bioinformatic analysis of sequenced bacterial genomes has uncovered an increasing number of natural product biosynthetic gene clusters to which no known bacterial metabolite can be ascribed. One emerging method we have investigated for studying these gene clusters is the synthetic-Bioinformatic Natural Product (syn-BNP) approach. The syn-BNP approach replaces transcription, translation and in vivo enzymatic biosynthesis of natural products with bioinformatic algorithms to predict the output of a gene cluster and in vitro chemical synthesis to produce the predicted structure. Here we report on expanding the syn-BNP approach to the design and synthesis of cyclic peptides inspired by nonribosomal peptide synthetase biosynthetic gene clusters associated with the human microbiota. While no syn-BNPs we tested inhibited the growth of the bacteria or yeast, five were found to be active in the human cell-based MTT metabolic activity assay. Interestingly, active peptides were mostly inspired by gene clusters found in the genomes of opportunistic pathogens that are often more commonly associated with environments outside the human microbiome. The cyclic syn-BNP studies presented here provide further evidence of its potential for identifying bioactive small molecules directly from the instructions encoded in the primary sequences of natural product biosynthetic gene clusters.}, }
@article {pmid31545522, year = {2019}, author = {Bosch, TCG}, title = {Multidisciplinary Approaches to Exploring Human-Microbiome Interactions.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {41}, number = {10}, pages = {1-2}, doi = {10.1002/bies.201900130}, pmid = {31545522}, issn = {1521-1878}, }
@article {pmid31537666, year = {2019}, author = {Yerushalmy, O and Coppenhagen-Glazer, S and Nir-Paz, R and Tuomala, H and Skurnik, M and Kiljunen, S and Hazan, R}, title = {Complete Genome Sequences of Two Klebsiella pneumoniae Phages Isolated as Part of an International Effort.}, journal = {Microbiology resource announcements}, volume = {8}, number = {38}, pages = {}, doi = {10.1128/MRA.00843-19}, pmid = {31537666}, issn = {2576-098X}, abstract = {We report the genomic sequences of phages KpCHEMY26 and KpGranit, isolated in Israel during a worldwide effort against a multidrug- and phage-resistant strain of Klebsiella pneumoniae from a patient in Finland. These results demonstrate the importance of an efficient worldwide network for collaborating in personalized therapy for infectious diseases.}, }
@article {pmid31533707, year = {2019}, author = {Willmann, M and Vehreschild, MJGT and Biehl, LM and Vogel, W and Dörfel, D and Hamprecht, A and Seifert, H and Autenrieth, IB and Peter, S}, title = {Distinct impact of antibiotics on the gut microbiome and resistome: a longitudinal multicenter cohort study.}, journal = {BMC biology}, volume = {17}, number = {1}, pages = {76}, doi = {10.1186/s12915-019-0692-y}, pmid = {31533707}, issn = {1741-7007}, support = {TTU 08.802//German Center for Infection Research/ ; }, abstract = {BACKGROUND: The selection pressure exercised by antibiotic drugs is an important consideration for the wise stewardship of antimicrobial treatment programs. Treatment decisions are currently based on crude assumptions, and there is an urgent need to develop a more quantitative knowledge base that can enable predictions of the impact of individual antibiotics on the human gut microbiome and resistome.<br><br>RESULTS: Using shotgun metagenomics, we quantified changes in the gut microbiome in two cohorts of hematological patients receiving prophylactic antibiotics; one cohort was treated with ciprofloxacin in a hospital in Tübingen and the other with cotrimoxazole in a hospital in Cologne. Analyzing this rich longitudinal dataset, we found that gut microbiome diversity was reduced in both treatment cohorts to a similar extent, while effects on the gut resistome differed. We observed a sharp increase in the relative abundance of sulfonamide antibiotic resistance genes (ARGs) by 148.1% per cumulative defined daily dose of cotrimoxazole in the Cologne cohort, but not in the Tübingen cohort treated with ciprofloxacin. Through multivariate modeling, we found that factors such as individual baseline microbiome, resistome, and plasmid diversity; liver/kidney function; and concurrent medication, especially virostatic agents, influence resistome alterations. Strikingly, we observed different effects on the plasmidome in the two treatment groups. There was a substantial increase in the abundance of ARG-carrying plasmids in the cohort treated with cotrimoxazole, but not in the cohort treated with ciprofloxacin, indicating that cotrimoxazole might contribute more efficiently to the spread of resistance.<br><br>CONCLUSIONS: Our study represents a step forward in developing the capability to predict the effect of individual antimicrobials on the human microbiome and resistome. Our results indicate that to achieve this, integration of the individual baseline microbiome, resistome, and mobilome status as well as additional individual patient factors will be required. Such personalized predictions may in the future increase patient safety and reduce the spread of resistance.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov, NCT02058888 . Registered February 10 2014.}, }
@article {pmid31532533, year = {2019}, author = {Bhuta, R and Nieder, M and Jubelirer, T and Ladas, EJ}, title = {The Gut Microbiome and Pediatric Cancer: Current Research and Gaps in Knowledge.}, journal = {Journal of the National Cancer Institute. Monographs}, volume = {2019}, number = {54}, pages = {169-173}, doi = {10.1093/jncimonographs/lgz026}, pmid = {31532533}, issn = {1745-6614}, abstract = {The human microbiome consists of trillions of microbial cells that interact with one another and the human host to play a clinically significant role in health and disease. Gut microbial changes have been identified in cancer pathogenesis, at disease diagnosis, during therapy, and even long after completion of treatment. Alterations in the gut microbiome have been linked to treatment-related toxicity and potential long-term morbidity and mortality in children with cancer. Such alterations are plausible given immune modulation due to disease as well as exposure to cytotoxic chemotherapy, infections, and antibiotics. The following review presents our current scientific understanding on the role of the gut microbiome in pediatric cancer, identifies gaps in knowledge, and suggests future research goals.}, }
@article {pmid31530872, year = {2019}, author = {Köberl, M and Erschen, S and Etemadi, M and White, RA and El-Arabi, TF and Berg, G}, title = {Deciphering the microbiome shift during fermentation of medicinal plants.}, journal = {Scientific reports}, volume = {9}, number = {1}, pages = {13461}, doi = {10.1038/s41598-019-49799-2}, pmid = {31530872}, issn = {2045-2322}, abstract = {The importance of the human-microbiome relationship for positive health outcomes has become more apparent over the last decade. Influencing the gut microbiome via modification of diet represents a possibility of maintaining a healthy gut flora. Fermented food and lactic acid bacteria (LAB) display a preventive way to inhibit microbial dysbioses and diseases, but their ecology on plants is poorly understood. We characterized the microbiome of medicinal plants (Matricaria chamomilla L. and Calendula officinalis L.) using 16S rRNA gene profiling from leaves that were fermented over a six-week time course. The unfermented samples were characterized by a distinct phyllosphere microbiome, while the endosphere revealed a high similarity. During fermentation, significant microbial shifts were observed, whereby LAB were enhanced in all approaches but never numerically dominated. Among the LAB, Enterococcaceae were identified as the most dominant family in both plants. M. chamomilla community had higher relative abundances of Lactobacillaceae and Carnobacteriaceae, while C. officinalis showed a higher presence of Leuconostocaceae and Streptococcaceae. The natural leaf microbiome and the indigenous LAB communities of field-grown Asteraceae medicinal plants are plant-specific and habitat-specific and are subjected to significant shifts during fermentation. Leaf surfaces as well as leaf endospheres were identified as sources for biopreservative LAB.}, }
@article {pmid31526326, year = {2019}, author = {Reid, G}, title = {Fourteen steps to relevance: taking probiotics from the bench to the consumer.}, journal = {Canadian journal of microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1139/cjm-2019-0148}, pmid = {31526326}, issn = {1480-3275}, abstract = {Much is made of the need to translate scientific research into improved care of people or other life forms. Grant applications invariably start with the extent of a problem, and end by claiming that their work will or could result in making an impact. In truth, very few projects ever lead to translation at the level of the host, nor was that really their intent. For those who are focused on applied science, there are many ways to reach the desired goal, sometimes through serendipity or by logical stepwise progress. The following paper will provide personal insight into the stages, pitfalls and ultimate assessment of relevance in the context of using probiotic lactobacilli for human health and other applications.}, }
@article {pmid31524305, year = {2019}, author = {Amato, KR and Jeyakumar, T and Poinar, H and Gros, P}, title = {Shifting Climates, Foods, and Diseases: The Human Microbiome through Evolution.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {}, number = {}, pages = {e1900034}, doi = {10.1002/bies.201900034}, pmid = {31524305}, issn = {1521-1878}, support = {Trottier Fellow in the Humans and the Microbiome P//Canadian Institute for Advanced Research/ ; }, abstract = {Human evolution has been punctuated by climate anomalies, structuring environments, deadly infections, and altering landscapes. How well humans adapted to these new circumstances had direct effects on fitness and survival. Here, how the gut microbiome could have contributed to human evolutionary success through contributions to host nutritional buffering and infectious disease resistance is reviewed. How changes in human genetics, diet, disease exposure, and social environments almost certainly altered microbial community composition is also explored. Emerging research points to the microbiome as a key player in host responses to environmental change. Therefore, the reciprocal interactions between humans and their microbes are likely to have shaped human patterns of local adaptation throughout our shared evolutionary history. Recent alterations in human lifestyle, however, are altering human microbiomes in unprecedented ways. The consequences of interrupted host-microbe relationships for human adaptive potential in the future are unknown.}, }
@article {pmid31522775, year = {2019}, author = {Requena, T and Velasco, M}, title = {The human microbiome in sickness and in health.}, journal = {Revista clinica espanola}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.rce.2019.07.004}, pmid = {31522775}, issn = {1578-1860}, abstract = {The study of the human microbiome has led to an exceptional increase in the current understanding of the importance of microbiota for health throughout all stages of life. Human microbial colonization occurs in the skin, genitourinary system and, mainly, in the oral cavity and intestinal tract. In these locations, the human microbiota establishes a symbiotic relationship with the host and helps maintain the physiological homeostasis. Lifestyle, age, diet and use of antibiotics are the main regulators of the composition and functionality of human microbiota. Recent studies have indicated the reduction in microbial diversity as one of the contributors to the development of diseases. In addition to phylogenetic diversity studies, further metagenomic studies are needed at the functional level of the human microbiome to improve our understanding of its involvement in human health.}, }
@article {pmid31520544, year = {2019}, author = {Polkowska-Pruszyńska, B and Gerkowicz, A and Krasowska, D}, title = {The gut microbiome alterations in allergic and inflammatory skin diseases - an update.}, journal = {Journal of the European Academy of Dermatology and Venereology : JEADV}, volume = {}, number = {}, pages = {}, doi = {10.1111/jdv.15951}, pmid = {31520544}, issn = {1468-3083}, abstract = {The human microbiome is a wide range of microorganisms residing in and on our body. The homeostasis between host immune system and the microbial environment allows mutual benefits and protection. Physiological bacterial colonization is essential for the establishment of organism immunity. The human microbiota ecosystem can be divided into several compartments, out of which intestinal flora strongly affects our health and plays a crucial role in the pathophysiology of many diseases. The gastrointestinal tract, being a major guardian of the immune system, maintains the homeostasis with the commensal microorganisms by tolerating the typical flora antigens. The dysbiosis may trigger an inflammatory response followed by tissue damage or autoimmune processes. The gut microbiome alterations are linked to the pathogenesis of the allergic, cardiovascular, gastrointestinal, metabolic, neurodevelopmental, psychiatric and neurodegenerative diseases and cancer. Moreover, there is increasing evidence connecting the skin condition with the gastrointestinal microbiome, which has been described as the skin-gut axis. The aim of this study was to review the literature regarding the role of the gut microbiome alterations in the pathogenesis of selected allergic and inflammatory skin diseases.}, }
@article {pmid31519129, year = {2019}, author = {Ndika, J and Seemab, U and Poon, WL and Fortino, V and El-Nezami, H and Karisola, P and Alenius, H}, title = {Silver, titanium dioxide, and zinc oxide nanoparticles trigger miRNA/isomiR expression changes in THP-1 cells that are proportional to their health hazard potential.}, journal = {Nanotoxicology}, volume = {}, number = {}, pages = {1-16}, doi = {10.1080/17435390.2019.1661040}, pmid = {31519129}, issn = {1743-5404}, abstract = {After over a decade of nanosafety research, it is indisputable that the vast majority of nano-sized particles induce a plethora of adverse cellular responses - the severity of which is linked to the material's physicochemical properties. Differentiated THP-1 cells were previously exposed for 6 h and 24 h to silver, titanium dioxide, and zinc oxide nanoparticles at the maximum molar concentration at which no more than 15% cellular cytotoxicity was observed. All three nanoparticles differed in extent of induction of biological pathways corresponding to immune response signaling and metal ion homeostasis. In this study, we integrated gene and miRNA expression profiles from the same cells to propose miRNA biomarkers of adverse exposure to metal-based nanoparticles. We employed RNA sequencing together with a quantitative strategy that also enables analysis of the overlooked repertoire of length and sequence miRNA variants called isomiRs. Whilst only modest changes in expression were observed within the first 6 h of exposure, the miRNA/isomiR (miR) profiles of each nanoparticle were unique. Via canonical correlation and pathway enrichment analyses, we identified a co-regulated miR-mRNA cluster, predicted to be highly relevant for cellular response to metal ion homeostasis. These miRs were annotated to be canonical or variant isoforms of hsa-miR-142-5p, -342-3p, -5100, -6087, -6894-3p, and -7704. Hsa-miR-5100 was differentially expressed in response to each nanoparticle in both the 6 h and 24 h exposures. Taken together, this co-regulated miR-mRNA cluster could represent potential biomarkers of sub-toxic metal-based nanoparticle exposure.}, }
@article {pmid31502535, year = {2019}, author = {Forsberg, KJ and Bhatt, IV and Schmidtke, DT and Javanmardi, K and Dillard, KE and Stoddard, BL and Finkelstein, IJ and Kaiser, BK and Malik, HS}, title = {Functional metagenomics-guided discovery of potent Cas9 inhibitors in the human microbiome.}, journal = {eLife}, volume = {8}, number = {}, pages = {}, doi = {10.7554/eLife.46540}, pmid = {31502535}, issn = {2050-084X}, support = {R01 GM105691/GM/NIGMS NIH HHS/United States ; F31 GM125201/GM/NIGMS NIH HHS/United States ; R01 GM124131/GM/NIGMS NIH HHS/United States ; F-1808//Welch Foundation/ ; }, abstract = {CRISPR-Cas systems protect bacteria and archaea from phages and other mobile genetic elements, which use small anti-CRISPR (Acr) proteins to overcome CRISPR-Cas immunity. Because Acrs are challenging to identify, their natural diversity and impact on microbial ecosystems are underappreciated. To overcome this discovery bottleneck, we developed a high-throughput functional selection to isolate ten DNA fragments from human oral and fecal metagenomes that inhibit Streptococcus pyogenes Cas9 (SpyCas9) in Escherichia coli. The most potent Acr from this set, AcrIIA11, was recovered from a Lachnospiraceae phage. We found that AcrIIA11 inhibits SpyCas9 in bacteria and in human cells. AcrIIA11 homologs are distributed across diverse bacteria; many distantly-related homologs inhibit both SpyCas9 and a divergent Cas9 from Treponema denticola. We find that AcrIIA11 antagonizes SpyCas9 using a different mechanism than other previously characterized Type II-A Acrs. Our study highlights the power of functional selection to uncover widespread Cas9 inhibitors within diverse microbiomes.}, }
@article {pmid31502171, year = {2020}, author = {Kumar, M and Singh, P and Murugesan, S and Vetizou, M and McCulloch, J and Badger, JH and Trinchieri, G and Al Khodor, S}, title = {Microbiome as an Immunological Modifier.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {2055}, number = {}, pages = {595-638}, doi = {10.1007/978-1-4939-9773-2_27}, pmid = {31502171}, issn = {1940-6029}, abstract = {Humans are living ecosystems composed of human cells and microbes. The microbiome is the collection of microbes (microbiota) and their genes. Recent breakthroughs in the high-throughput sequencing technologies have made it possible for us to understand the composition of the human microbiome. Launched by the National Institutes of Health in USA, the human microbiome project indicated that our bodies harbor a wide array of microbes, specific to each body site with interpersonal and intrapersonal variabilities. Numerous studies have indicated that several factors influence the development of the microbiome including genetics, diet, use of antibiotics, and lifestyle, among others. The microbiome and its mediators are in a continuous cross talk with the host immune system; hence, any imbalance on one side is reflected on the other. Dysbiosis (microbiota imbalance) was shown in many diseases and pathological conditions such as inflammatory bowel disease, celiac disease, multiple sclerosis, rheumatoid arthritis, asthma, diabetes, and cancer. The microbial composition mirrors inflammation variations in certain disease conditions, within various stages of the same disease; hence, it has the potential to be used as a biomarker.}, }
@article {pmid31180804, year = {2019}, author = {Mark Welch, JL and Dewhirst, FE and Borisy, GG}, title = {Biogeography of the Oral Microbiome: The Site-Specialist Hypothesis.}, journal = {Annual review of microbiology}, volume = {73}, number = {}, pages = {335-358}, doi = {10.1146/annurev-micro-090817-062503}, pmid = {31180804}, issn = {1545-3251}, abstract = {Microbial communities are complex and dynamic, composed of hundreds of taxa interacting across multiple spatial scales. Advances in sequencing and imaging technology have led to great strides in understanding both the composition and the spatial organization of these complex communities. In the human mouth, sequencing results indicate that distinct sites host microbial communities that not only are distinguishable but to a meaningful degree are composed of entirely different microbes. Imaging suggests that the spatial organization of these communities is also distinct. Together, the literature supports the idea that most oral microbes are site specialists. A clear understanding of microbiota structure at different sites in the mouth enables mechanistic studies, informs the generation of hypotheses, and strengthens the position of oral microbiology as a model system for microbial ecology in general.}, }
@article {pmid31495055, year = {2019}, author = {Boto, L and Pineda, M and Pineda, R}, title = {Potential impacts of horizontal gene transfer on human health and physiology and how anthropogenic activity can affect it.}, journal = {The FEBS journal}, volume = {}, number = {}, pages = {}, doi = {10.1111/febs.15054}, pmid = {31495055}, issn = {1742-4658}, abstract = {Horizontal gene transfer is widespread among Prokaryotes driving their evolution. In this paper we review the potential impact in humans of the horizontal gene transfer between prokaryotes living in close association with humans in two scenarios: horizontal transfer in human microbiomes and transfer between microbes living in human managed environments. Although our vision is focused on the possible impact of these transfers in the propagation of antibiotic resistance genes or pathogenicity determinants, we also discuss possible human physiological adaptations via gene transfer between resident and occasional bacteria in the human microbiome. This article is protected by copyright. All rights reserved.}, }
@article {pmid31493521, year = {2019}, author = {Fielding, RA and Reeves, AR and Jasuja, R and Liu, C and Barrett, BB and Lustgarten, MS}, title = {Muscle strength is increased in mice that are colonized with microbiota from high-functioning older adults.}, journal = {Experimental gerontology}, volume = {}, number = {}, pages = {110722}, doi = {10.1016/j.exger.2019.110722}, pmid = {31493521}, issn = {1873-6815}, abstract = {Evidence in support of a gut-muscle axis has been reported in rodents, but studies in older adult humans are limited. Accordingly, the primary goals of the present study were to compare gut microbiome composition in older adults that differed in terms of the percentage of whole body lean mass and physical functioning (high-functioning, HF, n = 18; low-functioning, LF, n = 11), and to evaluate the causative role of the gut microbiome on these variables by transferring fecal samples from older adults into germ-free mice. Family-level Prevotellaceae, genus-level Prevotella and Barnesiella, and the bacterial species Barnesiella intestinihominis were higher in HF older adults at the initial study visit, at a 1-month follow-up visit, in HF human fecal donors, and in HF-colonized mice, when compared with their LF counterparts. Grip strength was significantly increased by 6.4% in HF-, when compared with LF-colonized mice. In contrast, despite significant differences for the percentage of whole body lean mass and physical functioning when comparing the human fecal donors, the percentage of whole body lean mass and treadmill endurance capacity were not different when comparing human microbiome-containing mice. In sum, these data suggest a role for gut bacteria on the maintenance of muscle strength, but argue against a role for gut bacteria on the maintenance of the percentage of whole body lean mass or endurance capacity, findings that collectively add to elucidation of the gut-muscle axis in older adults.}, }
@article {pmid31493090, year = {2019}, author = {Wheeler, KM and Liss, MA}, title = {The Microbiome and Prostate Cancer Risk.}, journal = {Current urology reports}, volume = {20}, number = {10}, pages = {66}, doi = {10.1007/s11934-019-0922-4}, pmid = {31493090}, issn = {1534-6285}, abstract = {PURPOSE OF THE REVIEW: There is an abundance of evidence that the human microbiome plays an important and nuanced role in controlling human metabolism, immunity, and cancer. Herein we aim to review the most current research looking at prostate cancer and its link with the gut and genitourinary microbiome. There is now a host of evidence for a unique genitourinary (GU) microbiome. The prostate microbiota, to include viral, bacterial, fungal, and parasitic contributions, as assessed from formalin-fixed tissue is described nicely in the study by Banerjee et al. Further hierarchical analysis by this group found a unique microbiome signature for higher Gleason score cancers and validation PCR studies noted a marked number of viral genomic insertions into host DNA. Shretha et al. also recently established unique GU microbiomes in patients with prostate cancer or benign prostate pathology based on urine samples. The gut microbiome likely also has an indirect but significant role in prostate cancer development and treatment. Liss et al. and Golombos et al. found significant associations between specific gut microbiota and prostate cancer. Interestingly, the balance of inflammatory and anti-inflammatory bacterial lipopolysaccharides, production of bile salts, and metabolism of dietary fiber to short chain fatty acids all likely play important roles in creating systemic pro- or anti-carcinogenic states. In terms of prostate cancer treatment effects, Sfanos et al. noted a unique microbial signature in patients undergoing oral androgen deprivation therapy (ADT) as compared with prostate cancer patients not on ADT. Patients undergoing ADT also had enrichment of bacterial metabolic pathways promoting androgen synthesis. Together, these studies have identified a unique GU microbiome and linked both the GU microbiome and unique gut microbial signatures with prostate cancer and prostate cancer treatments. Whether this information can be used in cancer prevention, treatment, or diagnosis are areas of ongoing and active research.}, }
@article {pmid31492655, year = {2019}, author = {Soto-Perez, P and Bisanz, JE and Berry, JD and Lam, KN and Bondy-Denomy, J and Turnbaugh, PJ}, title = {CRISPR-Cas System of a Prevalent Human Gut Bacterium Reveals Hyper-targeting against Phages in a Human Virome Catalog.}, journal = {Cell host &amp; microbe}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.chom.2019.08.008}, pmid = {31492655}, issn = {1934-6069}, abstract = {Bacteriophages are abundant within the human gastrointestinal tract, yet their interactions with gut bacteria remain poorly understood, particularly with respect to CRISPR-Cas immunity. Here, we show that the type I-C CRISPR-Cas system in the prevalent gut Actinobacterium Eggerthella lenta is transcribed and sufficient for specific targeting of foreign and chromosomal DNA. Comparative analyses of E. lenta CRISPR-Cas systems across (meta)genomes revealed 2 distinct clades according to cas sequence similarity and spacer content. We assembled a human virome database (HuVirDB), encompassing 1,831 samples enriched for viral DNA, to identify protospacers. This revealed matches for a majority of spacers, a marked increase over other databases, and uncovered &quot;hyper-targeted&quot; phage sequences containing multiple protospacers targeted by several E. lenta strains. Finally, we determined the positional mismatch tolerance of observed spacer-protospacer pairs. This work emphasizes the utility of merging computational and experimental approaches for determining the function and targets of CRISPR-Cas systems.}, }
@article {pmid31492538, year = {2019}, author = {Wang, S and Ryan, CA and Boyaval, P and Dempsey, EM and Ross, RP and Stanton, C}, title = {Maternal Vertical Transmission Affecting Early-life Microbiota Development.}, journal = {Trends in microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.tim.2019.07.010}, pmid = {31492538}, issn = {1878-4380}, abstract = {The association of the human microbiome with health outcomes has attracted much interest toward its therapeutic manipulation. The likelihood of modulating the human microbiome in early life is high and offers great potential to exert profound effects on human development since the early microbiota shows more flexibility compared to that of adults. The human microbiota, being similar to human genetics, can be transmitted from mother to infant, providing insights into early microbiota acquisition, subsequent development, and potential opportunities for intervention. Here, we review adaptations of the maternal microbiota during pregnancy, birth, and infancy, the acquisition and succession of early-life microbiota, and highlight recent efforts to elucidate mother-to-infant microbiota transmission. We further discuss how the mother-to-infant microbial transmission is shaped; and finally we address potential directions for future studies to promote our understanding within this field.}, }
@article {pmid31489307, year = {2019}, author = {Cammarota, G and Putignani, L and Gasbarrini, A}, title = {Gut microbiome beats two to zero host genome.}, journal = {Hepatobiliary surgery and nutrition}, volume = {8}, number = {4}, pages = {378-380}, doi = {10.21037/hbsn.2019.02.03}, pmid = {31489307}, issn = {2304-3881}, }
@article {pmid31488215, year = {2019}, author = {Badal, VD and Wright, D and Katsis, Y and Kim, HC and Swafford, AD and Knight, R and Hsu, CN}, title = {Challenges in the construction of knowledge bases for human microbiome-disease associations.}, journal = {Microbiome}, volume = {7}, number = {1}, pages = {129}, doi = {10.1186/s40168-019-0742-2}, pmid = {31488215}, issn = {2049-2618}, support = {AI Horizons Network//International Business Machines Corporation/ ; }, abstract = {The last few years have seen tremendous growth in human microbiome research, with a particular focus on the links to both mental and physical health and disease. Medical and experimental settings provide initial sources of information about these links, but individual studies produce disconnected pieces of knowledge bounded in context by the perspective of expert researchers reading full-text publications. Building a knowledge base (KB) consolidating these disconnected pieces is an essential first step to democratize and accelerate the process of accessing the collective discoveries of human disease connections to the human microbiome. In this article, we survey the existing tools and development efforts that have been produced to capture portions of the information needed to construct a KB of all known human microbiome-disease associations and highlight the need for additional innovations in natural language processing (NLP), text mining, taxonomic representations, and field-wide vocabulary standardization in human microbiome research. Addressing these challenges will enable the construction of KBs that help identify new insights amenable to experimental validation and potentially clinical decision support.}, }
@article {pmid31481604, year = {2019}, author = {Basu Thakur, P and Long, AR and Nelson, BJ and Kumar, R and Rosenberg, AF and Gray, MJ}, title = {Complex Responses to Hydrogen Peroxide and Hypochlorous Acid by the Probiotic Bacterium Lactobacillus reuteri.}, journal = {mSystems}, volume = {4}, number = {5}, pages = {}, doi = {10.1128/mSystems.00453-19}, pmid = {31481604}, issn = {2379-5077}, abstract = {Inflammatory diseases of the gut are associated with increased intestinal oxygen concentrations and high levels of inflammatory oxidants, including hydrogen peroxide (H2O2) and hypochlorous acid (HOCl), which are antimicrobial compounds produced by the innate immune system. This contributes to dysbiotic changes in the gut microbiome, including increased populations of proinflammatory enterobacteria (Escherichia coli and related species) and decreased levels of health-associated anaerobic Firmicutes and Bacteroidetes The pathways for H2O2 and HOCl resistance in E. coli have been well studied, but little is known about how commensal and probiotic bacteria respond to inflammatory oxidants. In this work, we have characterized the transcriptomic response of the anti-inflammatory, gut-colonizing Gram-positive probiotic Lactobacillus reuteri to both H2O2 and HOCl. L. reuteri mounts distinct but overlapping responses to each of these stressors, and both gene expression and survival were strongly affected by the presence or absence of oxygen. Oxidative stress response in L. reuteri required several factors not found in enterobacteria, including the small heat shock protein Lo18, polyphosphate kinase 2, and RsiR, an L. reuteri-specific regulator of anti-inflammatory mechanisms.IMPORTANCE Reactive oxidants, including hydrogen peroxide and hypochlorous acid, are antimicrobial compounds produced by the immune system during inflammation. Little is known, however, about how many important types of bacteria present in the human microbiome respond to these oxidants, especially commensal and other health-associated species. We have now mapped the stress response to both H2O2 and HOCl in the intestinal lactic acid bacterium Lactobacillus reuteri.}, }
@article {pmid31478123, year = {2019}, author = {Abid, MB and Koh, CJ}, title = {Probiotics in health and disease: fooling Mother Nature?.}, journal = {Infection}, volume = {}, number = {}, pages = {}, doi = {10.1007/s15010-019-01351-0}, pmid = {31478123}, issn = {1439-0973}, abstract = {Probiotics are ubiquitous, consumption by the general public is common, and the dogma remains that they are beneficial for general and gut health. However, evolving evidence suggests a potentially &quot;harmful&quot; impact of many commercially available probiotics. There is also significant variability in formulations that leads to a lack of a universally acceptable definition of probiotics. In this perspective, we review the flaws with definition, relevant observational and randomized studies that showed both positive and negative impacts on health and disease, unbiased interpretation of key trials, emerging evidence from microbiome and immuno-oncological studies, and impact on systemic immunity. We propose that caution be exercised prior to endorsements of their illness-directed consumption and rampant general usage. As a deeper understanding of the human microbiome accrues and our ability to manipulate this complex ecosystem improves, the probiotic of tomorrow might be the precision tool that deals with diseases on a broad front. Gut microbiome, akin to fingerprints, is indigenous to an individual and 'one size fits all' prescription strategy should be discouraged until a more universally acceptable 'favorable taxa' or a 'personalized probiotic,' to complement an individual's native microbiota, gets fashioned.}, }
@article {pmid31475212, year = {2019}, author = {Godoy-Vitorino, F}, title = {Human microbial ecology and the rising new medicine.}, journal = {Annals of translational medicine}, volume = {7}, number = {14}, pages = {342}, doi = {10.21037/atm.2019.06.56}, pmid = {31475212}, issn = {2305-5839}, abstract = {The first life forms on earth were Prokaryotic, and the evolution of all Eukaryotic life occurred with the help of bacteria. Animal-associated microbiota also includes members of the archaea, fungi, protists, and viruses. The genomes of this host-associated microbial life are called the microbiome. Across the mammalian tree, microbiomes guarantee the development of immunity, physiology, and resistance to pathogens. In humans, all surfaces and cavities are colonized by a microbiome, maintained by a careful balance between the host response and its colonizers-thus humans are considered now supraorganisms. These microbiomes supply essential ecosystem services that benefit health through homeostasis, and the loss of the indigenous microbiota leads to dysbiosis, which can have significant consequences to disease. This educational review aims to describe the importance of human microbial ecology, explain the ecological terms applied to the study of the human microbiome, developments within the cutting-edge microbiome field, and implications to diagnostic and treatment.}, }
@article {pmid31474424, year = {2019}, author = {Derrien, M and Alvarez, AS and de Vos, WM}, title = {The Gut Microbiota in the First Decade of Life.}, journal = {Trends in microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.tim.2019.08.001}, pmid = {31474424}, issn = {1878-4380}, abstract = {Appreciation of the importance of the gut microbiome is growing, and it is becoming increasingly relevant to identify preventive or therapeutic solutions targeting it. The composition and function of the gut microbiota are relatively well described for infants (less than 3 years) and adults, but have been largely overlooked in pre-school (3-6 years) and primary school-age (6-12 years) children, as well as teenagers (12-18 years). Early reports suggested that the infant microbiota would attain an adult-like structure at the age of 3 years, but recent studies have suggested that microbiota development may take longer. This development time is of key importance because there is evidence to suggest that deviations in this development may have consequences in later life. In this review, we provide an overview of current knowledge concerning the gut microbiota, its evolution, variation, and response to dietary challenges during the first decade of life with a focus on healthy pre-school and primary school-age children (up to 12 years) from various populations around the globe. This knowledge should facilitate the identification of diet-based approaches targeting individuals of this age group, to promote the development of a healthy microbiota in later life.}, }
@article {pmid31473416, year = {2019}, author = {Yan, ZZ and Chen, QL and Zhang, YJ and He, JZ and Hu, HW}, title = {Antibiotic resistance in urban green spaces mirrors the pattern of industrial distribution.}, journal = {Environment international}, volume = {132}, number = {}, pages = {105106}, doi = {10.1016/j.envint.2019.105106}, pmid = {31473416}, issn = {1873-6750}, abstract = {Urban green spaces are closely related to the activities and health of urban residents. Turf grass and soil are two major interfaces between the environmental and human microbiome, which represent potential pathways for the spread of antibiotic resistance genes (ARGs) from environmental to human microbiome through skin-surface contact. However, the information regarding the prevalence of ARGs in urban green spaces and drivers in shaping their distribution patterns remain unclear. Here, we profiled a wide spectrum of ARGs in grass phyllosphere and soils from 40 urban parks across Greater Melbourne, Australia, using high throughput quantitative PCR. A total of 217 and 218 unique ARGs and MGEs were detected in grass phyllosphere and soils, respectively, conferring resistance to almost all major classes of antibiotics commonly used in human and animals. The plant microbiome contained a core resistome, which occupied >84% of the total abundance of ARGs. In contrast, no core resistome was identified in the soil microbiome. The difference between plant and soil resistome composition was attributed to the difference in bacterial community structure and intensity of environmental and anthropogenic influence. Most importantly, the abundance of ARGs in urban green spaces was significantly positively related to industrial factors including total number of business, number of manufacturing, and number of electricity, gas, water and waste services in the region. Structural equation models further revealed that industrial distribution was a major factor shaping the ARG profiles in urban green spaces after accounting for multiple drivers. These findings have important implications for mitigation of the potential risks posed by ARGs to urban residents.}, }
@article {pmid31464810, year = {2019}, author = {Putignani, L and Gasbarrini, A and Dallapiccola, B}, title = {Potential of multiomics technology in precision medicine.}, journal = {Current opinion in gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.1097/MOG.0000000000000589}, pmid = {31464810}, issn = {1531-7056}, abstract = {PURPOSE OF REVIEW: The 'precision medicine' refers to the generation of identification and classification criteria for advanced taxonomy of patients, exploiting advanced models to infer optimized clinical decisions for each disease phenotype.<br><br>RECENT FINDINGS: The current article reviews new advances in the past 18 months on the microbiomics science intended as new discipline contributing to advanced 'precision medicine'. Recently published data highlight the importance of multidimensional data in the description of deep disease phenotypes, including microbiome and immune profiling, and support the efficacy of the systems medicine to better stratify patients, hence optimizing diagnostics, clinical management and response to treatments.<br><br>SUMMARY: The articles referenced in this review help inform the reader on new decision-support systems that can be based on multiomics patients' data including microbiome and immune profiling. These harmonized and integrated data can be elaborated by artificial intelligence to generate optimized diagnostic pipelines and clinical interventions.}, }
@article {pmid31457107, year = {2018}, author = {Herd, P and Palloni, A and Rey, F and Dowd, JB}, title = {Social and population health science approaches to understand the human microbiome.}, journal = {Nature human behaviour}, volume = {2}, number = {11}, pages = {808-815}, doi = {10.1038/s41562-018-0452-y}, pmid = {31457107}, issn = {2397-3374}, support = {P30 AG017266/AG/NIA NIH HHS/United States ; R01 AG041868/AG/NIA NIH HHS/United States ; R21 AI121784/AI/NIAID NIH HHS/United States ; UL1 TR000427/TR/NCATS NIH HHS/United States ; }, abstract = {The microbiome is now considered our 'second genome' with potentially comparable importance to the genome in determining human health. There is, however, a relatively limited understanding of the broader environmental factors, particularly social conditions, that shape variation in human microbial communities. Fulfilling the promise of microbiome research - particularly the microbiome's potential for modification - will require collaboration between biologists and social and population scientists. For life scientists, the plasticity and adaptiveness of the microbiome calls for an agenda to understand the sensitivity of the microbiome to broader social environments already known to be powerful predictors of morbidity and mortality. For social and population scientists, attention to the microbiome may help answer nagging questions about the underlying biological mechanisms that link social conditions to health. We outline key substantive and methodological advances that can be made if collaborations between social and population health scientists and life scientists are strategically pursued.}, }
@article {pmid31456069, year = {2019}, author = {Chen, J and Douglass, J and Prasath, V and Neace, M and Atrchian, S and Manjili, MH and Shokouhi, S and Habibi, M}, title = {The microbiome and breast cancer: a review.}, journal = {Breast cancer research and treatment}, volume = {}, number = {}, pages = {}, doi = {10.1007/s10549-019-05407-5}, pmid = {31456069}, issn = {1573-7217}, abstract = {The human microbiome plays an integral role in physiology, with most microbes considered benign or beneficial. However, some microbes are known to be detrimental to human health, including organisms linked to cancers and other diseases characterized by aberrant inflammation. Dysbiosis, a state of microbial imbalance with harmful bacteria species outcompeting benign bacteria, can lead to maladies including cancer. The microbial composition varies across body sites, with the gut, urogenital, and skin microbiomes particularly well characterized. However, the microbiome associated with normal breast tissue and breast diseases is poorly understood. Collectively, studies have shown that breast tissue has a distinct microbiome with particular species enriched in the breast tissue itself, as well as the nipple aspirate and gut bacteria of women with breast cancer. More importantly, the breast and associated microbiomes may modulate therapeutic response and serve as potential biomarkers for diagnosing and staging breast cancer.}, }
@article {pmid31455640, year = {2019}, author = {Creekmore, BC and Gray, JH and Walton, WG and Biernat, KA and Little, MS and Xu, Y and Liu, J and Gharaibeh, RZ and Redinbo, MR}, title = {Mouse Gut Microbiome-Encoded β-Glucuronidases Identified Using Metagenome Analysis Guided by Protein Structure.}, journal = {mSystems}, volume = {4}, number = {4}, pages = {}, doi = {10.1128/mSystems.00452-19}, pmid = {31455640}, issn = {2379-5077}, abstract = {Gut microbial β-glucuronidase (GUS) enzymes play important roles in drug efficacy and toxicity, intestinal carcinogenesis, and mammalian-microbial symbiosis. Recently, the first catalog of human gut GUS proteins was provided for the Human Microbiome Project stool sample database and revealed 279 unique GUS enzymes organized into six categories based on active-site structural features. Because mice represent a model biomedical research organism, here we provide an analogous catalog of mouse intestinal microbial GUS proteins-a mouse gut GUSome. Using metagenome analysis guided by protein structure, we examined 2.5 million unique proteins from a comprehensive mouse gut metagenome created from several mouse strains, providers, housing conditions, and diets. We identified 444 unique GUS proteins and organized them into six categories based on active-site features, similarly to the human GUSome analysis. GUS enzymes were encoded by the major gut microbial phyla, including Firmicutes (60%) and Bacteroidetes (21%), and there were nearly 20% for which taxonomy could not be assigned. No differences in gut microbial gus gene composition were observed for mice based on sex. However, mice exhibited gus differences based on active-site features associated with provider, location, strain, and diet. Furthermore, diet yielded the largest differences in gus composition. Biochemical analysis of two low-fat-associated GUS enzymes revealed that they are variable with respect to their efficacy of processing both sulfated and nonsulfated heparan nonasaccharides containing terminal glucuronides.IMPORTANCE Mice are commonly employed as model organisms of mammalian disease; as such, our understanding of the compositions of their gut microbiomes is critical to appreciating how the mouse and human gastrointestinal tracts mirror one another. GUS enzymes, with importance in normal physiology and disease, are an attractive set of proteins to use for such analyses. Here we show that while the specific GUS enzymes differ at the sequence level, a core GUSome functionality appears conserved between mouse and human gastrointestinal bacteria. Mouse strain, provider, housing location, and diet exhibit distinct GUSomes and gus gene compositions, but sex seems not to affect the GUSome. These data provide a basis for understanding the gut microbial GUS enzymes present in commonly used laboratory mice. Further, they demonstrate the utility of metagenome analysis guided by protein structure to provide specific sets of functionally related proteins from whole-genome metagenome sequencing data.}, }
@article {pmid31455639, year = {2019}, author = {Cao, L and Shcherbin, E and Mohimani, H}, title = {A Metabolome- and Metagenome-Wide Association Network Reveals Microbial Natural Products and Microbial Biotransformation Products from the Human Microbiota.}, journal = {mSystems}, volume = {4}, number = {4}, pages = {}, doi = {10.1128/mSystems.00387-19}, pmid = {31455639}, issn = {2379-5077}, abstract = {The human microbiome consists of thousands of different microbial species, and tens of thousands of bioactive small molecules are associated with them. These associated molecules include the biosynthetic products of microbiota and the products of microbial transformation of host molecules, dietary components, and pharmaceuticals. The existing methods for characterization of these small molecules are currently time consuming and expensive, and they are limited to the cultivable bacteria. Here, we propose a method for detecting microbiota-associated small molecules based on the patterns of cooccurrence of molecular and microbial features across multiple microbiomes. We further map each molecule to the clade in a phylogenetic tree that is responsible for its production/transformation. We applied our proposed method to the tandem mass spectrometry and metagenomics data sets collected by the American Gut Project and to microbiome isolates from cystic fibrosis patients and discovered the genes in the human microbiome responsible for the production of corynomycolenic acid, which serves as a ligand for human T cells and induces a specific immune response against infection. Moreover, our method correctly associated pseudomonas quinolone signals, tyrvalin, and phevalin with their known biosynthetic gene clusters.IMPORTANCE Experimental advances have enabled the acquisition of tandem mass spectrometry and metagenomics sequencing data from tens of thousands of environmental/host-oriented microbial communities. Each of these communities contains hundreds of microbial features (corresponding to microbial species) and thousands of molecular features (corresponding to microbial natural products). However, with the current technology, it is very difficult to identify the microbial species responsible for the production/biotransformation of each molecular feature. Here, we develop association networks, a new approach for identifying the microbial producer/biotransformer of natural products through cooccurrence analysis of metagenomics and mass spectrometry data collected on multiple microbiomes.}, }
@article {pmid31448542, year = {2019}, author = {Brüssow, H}, title = {Problems with the concept of gut microbiota dysbiosis.}, journal = {Microbial biotechnology}, volume = {}, number = {}, pages = {}, doi = {10.1111/1751-7915.13479}, pmid = {31448542}, issn = {1751-7915}, abstract = {The human microbiome research is with the notable exception of fecal transplantation still mostly in a descriptive phase. Part of the difficulty for translating research into medical interventions is due to the large compositional complexity of the microbiome resulting in datasets that need sophisticated statistical methods for their analysis and do not lend to industrial applications. Another part of the difficulty might be due to logical flaws in terminology particularly concerning 'dysbiosis' that avoids circular conclusions and is based on sound ecological and evolutionary reasoning. Many case-control studies are underpowered necessitating more meta-analyses that sort out consistent from spurious dysbiosis-disease associations. We also need for the microbiome a transition from statistical associations to causal relationships with diseases that fulfil a set of modified Koch's postulates for commensals. Disturbingly, the most sophisticated statistical analyses explain only a small percentage of the variance in the microbiome. Microbe-microbe interactions irrelevant to the host and stochastic processes might play a greater role than anticipated. To satisfy the concept of Karl Popper about conjectures and refutations in the scientific process, we should also conduct more experiments that try to refute the role of the commensal gut microbiota for human health and disease.}, }
@article {pmid31443276, year = {2019}, author = {Satokari, R}, title = {Modulation of Gut Microbiota for Health by Current and Next-Generation Probiotics.}, journal = {Nutrients}, volume = {11}, number = {8}, pages = {}, doi = {10.3390/nu11081921}, pmid = {31443276}, issn = {2072-6643}, support = {304490, 323156//Academy of Finland/ ; Senior Fellow Grant//Sigrid Juséliuksen Säätiö/ ; }, abstract = {The human gut microbiota is a complex ecosystem and has an essential role in maintaining intestinal and systemic health. Microbiota dysbiosis is associated with a number of intestinal and systemic conditions and its modulation for human health is of great interest. Gut microbiota is a source of novel health-promoting bacteria, often termed as next-generation probiotics in order to distinguish them from traditional probiotics. The previous lessons learned with traditional probiotics can help the development of next-generation probiotics that target specific health issues and needs.}, }
@article {pmid31442396, year = {2019}, author = {Mittelman, K and Burstein, D}, title = {Tiny Hidden Genes within Our Microbiome.}, journal = {Cell}, volume = {178}, number = {5}, pages = {1034-1035}, doi = {10.1016/j.cell.2019.07.039}, pmid = {31442396}, issn = {1097-4172}, abstract = {Exploration of tiny protein-coding sequences within the human microbiome reveals thousands of conserved gene families that have been overlooked by traditional analyses. These small proteins may play key roles in the crosstalk among bacteria within the microbiome and in interactions with their human hosts.}, }
@article {pmid31440433, year = {2019}, author = {Mu, X and Zhao, C and Yang, J and Wei, X and Zhang, J and Liang, C and Gai, Z and Zhang, C and Zhu, D and Wang, Y and Zhang, L}, title = {Group B Streptococcus colonization induces Prevotella and Megasphaera abundance-featured vaginal microbiome compositional change in non-pregnant women.}, journal = {PeerJ}, volume = {7}, number = {}, pages = {e7474}, doi = {10.7717/peerj.7474}, pmid = {31440433}, issn = {2167-8359}, abstract = {Background: Previous studies have indicated that variations in the vaginal microbiome result in symptomatic conditions. Group B Streptococcus (GBS) is a significant neonatal pathogen and maternal vaginal colonization has been recognized as an important risk factor for neonatal disease. Therefore, it is important to discover the relationship between the composition of the vaginal microbiome and GBS colonization. This study explores the potential relationship between the composition of the vaginal microbiome and GBS colonization in non-pregnant Chinese women.<br><br>Methods: A total of 22 GBS-positive, non-pregnant women and 44 matched GBS-negative women were recruited for the current study. The composition of the vaginal microbiome was profiled by sequencing the 16S rRNA genes. The microbiome diversity and variation were then evaluated.<br><br>Results: The vaginal microbiome of the 66 subjects enrolled in the current study were compared and the results showed that GBS-positive women exhibited significant vaginal microbial differences compared with the GBS-negative women based on the analysis of similarities (r = 0.306, p < 0.01). The relative abundance of the bacterial genus Lactobacillus (p < 0.01) was significantly lower in the GBS-positive group, while the abundances of the bacterial genera Prevotella (p < 0.01), Megasphaera (p < 0.01), and Streptococcus (p < 0.01) were significantly higher in the GBS-positive group.<br><br>Discussion: The current study addressed significant variations across the communities of the vaginal microbiome in GBS-positive and GBS-negative women in a Chinese cohort, which paves the way for a larger cohort-based clinical validation study and the development of therapeutic probiotics in the future.}, }
@article {pmid31440325, year = {2019}, author = {Guo, J and Lv, Q and Ariff, A and Zhang, X and Peacock, CS and Song, Y and Wen, X and Saiganesh, A and Melton, PE and Dykes, GA and Moses, EK and LE Souëf, PN and Lu, F and Zhang, G}, title = {Western oropharyngeal and gut microbial profiles are associated with allergic conditions in Chinese immigrant children.}, journal = {The World Allergy Organization journal}, volume = {12}, number = {8}, pages = {100051}, doi = {10.1016/j.waojou.2019.100051}, pmid = {31440325}, issn = {1939-4551}, abstract = {Background: The allergy epidemic resulting from western environment/lifestyles is potentially due to modifications of the human microbiome. Therefore, it is of interest to study immigrants living in a western environment as well as their counterparts in the country of origin to understand differences in their microbiomes and health status.<br><br>Methods: We investigated 58 Australian Chinese (AC) children from Perth, Western Australia as well as 63 Chinese-born Chinese (CC) children from a city in China. Oropharyngeal (OP) and fecal samples were collected. To assess the microbiomes, 16s ribosomal RNA (rRNA) sequencing for variable regions V3 and V4 was used. Skin prick tests (SPT) were performed to measure the children's atopic status. Information on food allergy and wheezing were acquired from a questionnaire.<br><br>Results: AC children had more allergic conditions than CC children. The alpha diversity (mean species diversity) of both OP and gut microbiome was lower in AC children compared to CC children for richness estimate (Chao1), while diversity evenness (Shannon index) was higher. The beta diversity (community similarity) displayed a distinct separation of the OP and gut microbiota between AC and CC children. An apparent difference in microbial abundance was observed for many bacteria. In AC children, we sought to establish consistent trends in bacterial relative abundance that are either higher or lower in AC versus CC children and higher or lower in children with allergy versus those without allergy. The majority of OP taxa showed a consistent trend while the majority of fecal taxa showed a contrasting trend.<br><br>Conclusion: Distinct differences in microbiome compositions were found in both oropharyngeal and fecal samples of AC and CC children. The association of the OP microbiome with allergic condition is different from that of the gut microbiome in AC children. The microbiome profiles are changed by the western environment/lifestyle and are associated with allergies in Chinese immigrant children in Australia.}, }
@article {pmid31437194, year = {2019}, author = {Pendegraft, AH and Guo, B and Yi, N}, title = {Bayesian hierarchical negative binomial models for multivariable analyses with applications to human microbiome count data.}, journal = {PloS one}, volume = {14}, number = {8}, pages = {e0220961}, doi = {10.1371/journal.pone.0220961}, pmid = {31437194}, issn = {1932-6203}, abstract = {The analyses of large volumes of metagenomic data extracted from aggregate populations of microscopic organisms residing on and in the human body are advancing contemporary understandings of the integrated participation of microbes in human health and disease. Next generation sequencing technology facilitates said analyses in terms of diversity, community composition, and differential abundance by filtering and binning microbial 16S rRNA genes extracted from human tissues into operational taxonomic units. However, current statistical tools restrict study designs to investigations of limited numbers of host characteristics mediated by limited numbers of samples potentially yielding a loss of relevant information. This paper presents a Bayesian hierarchical negative binomial model as an efficient technique capable of compensating for multivariable sets including tens or hundreds of host characteristics as covariates further expanding analyses of human microbiome count data. Simulation studies reveal that the Bayesian hierarchical negative binomial model provides a desirable strategy by often outperforming three competing negative binomial model in terms of type I error while simultaneously maintaining consistent power. An application of the Bayesian hierarchical negative binomial model using subsets of the open data published by the American Gut Project demonstrates an ability to identify operational taxonomic units significantly differentiable among persons diagnosed by a medical professional with either inflammatory bowel disease or irritable bowel syndrome that are consistent with contemporary gastrointestinal literature.}, }
@article {pmid31433970, year = {2019}, author = {Spencer, SP and Fragiadakis, GK and Sonnenburg, JL}, title = {Pursuing Human-Relevant Gut Microbiota-Immune Interactions.}, journal = {Immunity}, volume = {51}, number = {2}, pages = {225-239}, doi = {10.1016/j.immuni.2019.08.002}, pmid = {31433970}, issn = {1097-4180}, abstract = {The gut microbiota is a complex and plastic network of diverse organisms intricately connected with human physiology. Recent advances in profiling approaches of both the microbiota and the immune system now enable a deeper exploration of immunity-microbiota connections. An important next step is to elucidate a human-relevant &quot;map&quot; of microbial-immune wiring while focusing on animal studies to probe a prioritized subset of interactions. Here, we provide an overview of this field's current status and discuss two approaches for establishing priorities for detailed investigation: (1) longitudinal intervention studies in humans probing the dynamics of both the microbiota and the immune system and (2) the study of traditional populations to assess lost features of human microbial identity whose absence may be contributing to the rise of immunological disorders. These human-centered approaches offer a judicious path forward to understand the impact of the microbiota in immune development and function.}, }
@article {pmid31425594, year = {2019}, author = {Mougeot, JC and Stevens, CB and Morton, DS and Brennan, MT and Mougeot, FB}, title = {Oral Microbiome and Cancer Therapy-Induced Oral Mucositis.}, journal = {Journal of the National Cancer Institute. Monographs}, volume = {2019}, number = {53}, pages = {}, doi = {10.1093/jncimonographs/lgz002}, pmid = {31425594}, issn = {1745-6614}, abstract = {Characterization of the role of oral microbiome in cancer therapy-induced oral mucositis (CTOM) is critical in preventing the clinically deleterious effects on patients' health that are associated with CTOM. Funding initiatives related to the National Institutes of Health human microbiome project have resulted in groundbreaking advancements in biology and medicine during the last decade. These advancements have shown that a human being is in fact a superorganism made of human cells and associated symbiotic or commensal microbiota. In this review, we describe the state of science as it relates to fundamental knowledge on oral microbiome and its role in CTOM. We also discuss how state-of-the-art technologies and systems biology tools may be used to help tackle the difficult challenges ahead to develop effective treatments or preventive therapies for oral mucositis. We make a clear distinction between disease processes pertaining to the oral microbiome, which includes opportunistic pathogens that may be defined as pathobionts, and those infectious disease processes initiated by exogenous pathogens. We also explored the extent to which knowledge from the gastrointestinal tract in disease and intestinal mucositis could help us better understand CTOM pathobiology. Finally, we propose a model in which the oral microbiome participates in the current five-step CTOM pathobiology model. With the advent of more sophisticated metagenomics technologies and methods of analysis, much hope lies ahead to implement an effective holistic approach to treat cancer patients affected by CTOM.}, }
@article {pmid31417531, year = {2019}, author = {Conteville, LC and Oliveira-Ferreira, J and Vicente, ACP}, title = {Gut Microbiome Biomarkers and Functional Diversity Within an Amazonian Semi-Nomadic Hunter-Gatherer Group.}, journal = {Frontiers in microbiology}, volume = {10}, number = {}, pages = {1743}, doi = {10.3389/fmicb.2019.01743}, pmid = {31417531}, issn = {1664-302X}, abstract = {Human groups that still maintain traditional modes of subsistence (hunter-gatherers and rural agriculturalists) represent human groups non-impacted by urban-industrialized lifestyles, and therefore their gut microbiome provides the basis for understanding the human microbiome evolution and its association with human health and disease. The Yanomami is the largest semi-nomadic hunter-gatherer group of the Americas, exploring different niches of the Amazon rainforest in Brazil and Venezuela. Here, based on shotgun metagenomic data, we characterized the gut microbiome of the Yanomami from Brazil and compared taxonomically and functionally with the Yanomami from Venezuela, with other traditional groups from the Amazon and an urban-industrialized group. Taxonomic biomarkers were identified to each South American traditional group studied, including each Yanomami group. Broader levels of functional categories poorly discriminated the traditional and urban-industrialized groups, but the stratification of these categories revealed clear segregation of these groups. The Yanomami/Brazil gut microbiome presented unique functional features, such as a higher abundance of gene families involved in regulation/cell signaling, motility/chemotaxis, and virulence, contrasting with the gut microbiomes from the Yanomami/Venezuela and the other groups. Our study revealed biomarkers, and taxonomic and functional features that distinguished the gut microbiome of Yanomami/Brazil and Yanomami/Venezuela individuals, despite their shared lifestyle, culture, and genetic background. These differences may be a reflection of the environmental and seasonal diversity of the niches they explore. Overall, their microbiome profiles are shared with South American and African traditional groups, probably due to their lifestyle. The unique features identified within the Yanomami highlight the bias imposed by underrepresented sampling, and factors such as variations over space and time (seasonality) that impact, mainly, the hunter-gatherers.}, }
@article {pmid31417492, year = {2019}, author = {Sudo, N}, title = {Biogenic Amines: Signals Between Commensal Microbiota and Gut Physiology.}, journal = {Frontiers in endocrinology}, volume = {10}, number = {}, pages = {504}, doi = {10.3389/fendo.2019.00504}, pmid = {31417492}, issn = {1664-2392}, abstract = {There is increasing interest in the interactions among the gut microbiota, gut, and brain, which is often referred to as the &quot;microbiota-gut-brain&quot; axis. Biogenic amines including dopamine, norepinephrine, serotonin, and histamines are all generated by commensal gut microorganisms and are suggested to play roles as signaling molecules mediating the function of the &quot;microbiota-gut-brain&quot; axis. In addition, such amines generated in the gut have attracted attention in terms of possible clues into the etiologies of depression, anxiety, and even psychosis. This review covers the latest research related to the potential role of microbe-derived amines such as catecholamine, serotonin, histamine, as well as other trace amines, in modulating not only gut physiology but also brain function of the host. Further attention in this field can offer not only insight into expanding the fundamental roles and impacts of the human microbiome, but also further offer new therapeutic strategies for psychological disorders based on regulating the balance of resident bacteria.}, }
@article {pmid31417479, year = {2019}, author = {Lacorte, E and Gervasi, G and Bacigalupo, I and Vanacore, N and Raucci, U and Parisi, P}, title = {A Systematic Review of the Microbiome in Children With Neurodevelopmental Disorders.}, journal = {Frontiers in neurology}, volume = {10}, number = {}, pages = {727}, doi = {10.3389/fneur.2019.00727}, pmid = {31417479}, issn = {1664-2295}, abstract = {Background and Purpose: A relationship between gut microbiome and central nervous system (CNS), have been suggested. The human microbiome may have an influence on brain's development, thus implying that dysbiosis may contribute in the etiology and progression of some neurological/neuropsychiatric disorders. The objective of this systematic review was to identify evidence on the characterization and potential distinctive traits of the microbiome of children with neurodevelopmental disorders, as compared to healthy children. Methods: The review was performed following the methodology described in the Cochrane handbook for systematic reviews, and was reported based on the PRISMA statement for reporting systematic reviews and meta-analyses. All literature published up to April 2019 was retrieved searching the databases PubMed, ISI Web of Science and the Cochrane Database of Systematic Reviews. Only observational studies, published in English and reporting data on the characterization of the microbiome in humans aged 0-18 years with a neurodevelopmental disorder were included. Neurodevelopmental disorders were categorized according to the definition included in the Diagnostic and Statistical Manual of Mental Disorders, version 5 (DSM-5). Results: Bibliographic searches yielded 9,237 records. One study was identified through other data sources. A total of 16 studies were selected based on their relevance and pertinence to the topic of the review, and were then applied the predefined inclusion and exclusion criteria. A total of 10 case-control studies met the inclusion criteria, and were thus included in the qualitative analysis and applied the NOS score. Two studies reported data on the gut microbiome of children with ADHD, while 8 reported data on either the gut (n = 6) or the oral microbiome (n = 2) of children with ASD. Conclusions: All the 10 studies included in this review showed a high heterogeneity in terms of sample size, gender, clinical issues, and type of controls. This high heterogeneity, along with the small sample size of the included studies, strongly limited the external validity of results. The quality assessment performed using the NOS score showed an overall low to moderate methodological quality of the included studies. To better clarify the potential role of microbiome in patients with neurodevelopmental disorders, further high-quality observational (specifically cohort) studies are needed.}, }
@article {pmid31415755, year = {2019}, author = {Tierney, BT and Yang, Z and Luber, JM and Beaudin, M and Wibowo, MC and Baek, C and Mehlenbacher, E and Patel, CJ and Kostic, AD}, title = {The Landscape of Genetic Content in the Gut and Oral Human Microbiome.}, journal = {Cell host &amp; microbe}, volume = {26}, number = {2}, pages = {283-295.e8}, doi = {10.1016/j.chom.2019.07.008}, pmid = {31415755}, issn = {1934-6069}, support = {T32 DK110919/DK/NIDDK NIH HHS/United States ; R00 ES023504/ES/NIEHS NIH HHS/United States ; R21 ES025052/ES/NIEHS NIH HHS/United States ; R01 AI127250/AI/NIAID NIH HHS/United States ; K99 ES023504/ES/NIEHS NIH HHS/United States ; }, abstract = {Despite substantial interest in the species diversity of the human microbiome and its role in disease, the scale of its genetic diversity, which is fundamental to deciphering human-microbe interactions, has not been quantified. Here, we conducted a cross-study meta-analysis of metagenomes from two human body niches, the mouth and gut, covering 3,655 samples from 13 studies. We found staggering genetic heterogeneity in the dataset, identifying a total of 45,666,334 non-redundant genes (23,961,508 oral and 22,254,436 gut) at the 95% identity level. Fifty percent of all genes were &quot;singletons,&quot; or unique to a single metagenomic sample. Singletons were enriched for different functions (compared with non-singletons) and arose from sub-population-specific microbial strains. Overall, these results provide potential bases for the unexplained heterogeneity observed in microbiome-derived human phenotypes. One the basis of these data, we built a resource, which can be accessed at https://microbial-genes.bio.}, }
@article {pmid31410749, year = {2019}, author = {Zhang, F and Wang, M and Yang, J and Xu, Q and Liang, C and Chen, B and Zhang, J and Yang, Y and Wang, H and Shang, Y and Wang, Y and Mu, X and Zhu, D and Zhang, C and Yao, M and Zhang, L}, title = {Response of gut microbiota in type 2 diabetes to hypoglycemic agents.}, journal = {Endocrine}, volume = {}, number = {}, pages = {}, doi = {10.1007/s12020-019-02041-5}, pmid = {31410749}, issn = {1559-0100}, abstract = {PURPOSE: Accumulated evidence has indicated that the gut microbiome affected the pharmacology of anti-diabetic agents, and their metabolic products induced by the agents transformed the structure of gastrointestinal microbiota in return. However, the studies around heredity, ethnicity, or living condition, referring to human microbiome were mostly represented by an occidental pattern partial and rare studies that focused on the effect of several first-line hypoglycemic agents on the gut flora in a single medical center. Therefore, we aimed to explore the interaction between gut microbiome and type 2 diabetes (T2D) or hypoglycemics in Chinese population.<br><br>METHODS: A total of 130 T2D patients with a specific hypoglycemic treatment and 50 healthy volunteers were enrolled in this study. Gut microbiome compositons were analyzed by 16S ribosomal RNA gene-based sequencing protocol.<br><br>RESULTS: Hypoglycemic agents contributed to the alteration of specific species in gut bacteria rather than its total diversity. Metformin increased the abundance of Spirochaete, Turicibacter, and Fusobacterium. Insulin also increased Fusobacterium, and α-glucosidase inhibitors (α-GIs) contributed to the plentitude of Bifidobacterium and Lactobacillus. Both metformin and insulin improved taurine and hypotaurine metabolism, and α-GI promoted several amino acid pathways. Although the community of gut microbiota with metformin and insulin showed similarity, significant differences were available in each diabetic group with hypoglycemia.<br><br>CONCLUSIONS: Gut microbiota is significantly associated with anti-diabetic agents. The gut microbiome and metabolism have shown respective characteristics in different T2D groups, which were also significantly different from the healthy group. This study provides some new insights for identification and exploration of the pathogenesis of T2D.}, }
@article {pmid31409863, year = {2019}, author = {Pereira, EM and de Mattos, CS and Dos Santos, OC and Ferreira, DC and de Oliveira, TLR and Laport, MS and de Oliveira Ferreira, E and Dos Santos, KRN}, title = {Staphylococcus hominis subspecies can be identified by SDS-PAGE or MALDI-TOF MS profiles.}, journal = {Scientific reports}, volume = {9}, number = {1}, pages = {11736}, doi = {10.1038/s41598-019-48248-4}, pmid = {31409863}, issn = {2045-2322}, abstract = {Staphylococcus hominis is part of the normal human microbiome. Two subspecies, S. hominis hominis (Shh) and S. hominis novobiosepticus (Shn), have clinical significance. Forty-nine S. hominis isolates were analyzed by the MicroScan automated system, SDS-PAGE and MALDI-TOF methods, followed by partial sequencing of the 16S rDNA gene. The trehalose fermentation test, disk diffusion and broth microdilution tests were used to identify (novobiocin test) and access the susceptibility to oxacillin and vancomycin of isolates. The SCCmec elements and genomic diversity were evaluated by PCR and PFGE methods, respectively. Profiles of 28 (57%; 8 Shh and 20 Shn) isolates corroborated with the results found in all the applied methods of identification. The remaining 21 (43%) isolates were phenotypically identified as Shh by MicroScan; however, they were identified as Shn by SDS-PAGE and mass spectral, and confirmed by 16S rDNA sequencing. Among 41 isolates identified as Shn by the molecular and mass spectrometry methods, 19 (41%) were novobiocin-sensitive, and the trehalose test indicated 11 positive isolates, which are considered atypical phenotypic results for this subspecies. In addition, 92.7% of the isolates identified as Shn by these methods carried mecA gene, while only 12.5% of the Shh isolates were positive. Together, the results highlighted the SDS-PAGE and MALDI-TOF MS methods as promising tools for discriminating S. hominis subspecies.}, }
@article {pmid31406314, year = {2019}, author = {}, title = {Vast pool of new proteins is found, thanks to the human microbiome.}, journal = {Nature}, volume = {572}, number = {7769}, pages = {287}, doi = {10.1038/d41586-019-02404-y}, pmid = {31406314}, issn = {1476-4687}, }
@article {pmid31402904, year = {2019}, author = {Gargiullo, L and Del Chierico, F and D'Argenio, P and Putignani, L}, title = {Gut Microbiota Modulation for Multidrug-Resistant Organism Decolonization: Present and Future Perspectives.}, journal = {Frontiers in microbiology}, volume = {10}, number = {}, pages = {1704}, doi = {10.3389/fmicb.2019.01704}, pmid = {31402904}, issn = {1664-302X}, abstract = {The emergence of antimicrobial resistance (AMR) is of great concern to global public health. Treatment of multi-drug resistant (MDR) infections is a major clinical challenge: the increase in antibiotic resistance leads to a greater risk of therapeutic failure, relapses, longer hospitalizations, and worse clinical outcomes. Currently, there are no validated treatments for many MDR or pandrug-resistant (PDR) infections, and preventing the spread of these pathogens through hospital infection control procedures and antimicrobial stewardship programs is often the only tool available to healthcare providers. Therefore, new solutions to control the colonization of MDR pathogens are urgently needed. In this narrative review, we discuss current knowledge of microbiota-mediated mechanisms of AMR and strategies for MDR colonization control. We focus particularly on fecal microbiota transplantation for MDR intestinal decolonization and report updated literature on its current clinical use.}, }
@article {pmid31402586, year = {2019}, author = {Mora, D and Filardi, R and Arioli, S and Boeren, S and Aalvink, S and de Vos, WM}, title = {Development of omics-based protocols for the microbiological characterization of multi-strain formulations marketed as probiotics: the case of VSL#3.}, journal = {Microbial biotechnology}, volume = {}, number = {}, pages = {}, doi = {10.1111/1751-7915.13476}, pmid = {31402586}, issn = {1751-7915}, support = {//Netherlands Organization for Scientific Research/ ; }, abstract = {The growing commercial interest in multi-strain formulations marketed as probiotics has not been accompanied by an equal increase in the evaluation of quality levels of these biotechnological products. The multi-strain product VSL#3 was used as a model to setup a microbiological characterization that could be extended to other formulations with high complexity. Shotgun metagenomics by deep Illumina sequencing was applied to DNA isolated from the commercial VSL#3 product to confirm strains identity safety and composition. Single-cell analysis was used to evaluate the cell viability, and β-galactosidase and urease activity have been used as marker to monitor the reproducibility of the production process. Similarly, these lots were characterized in detail by a metaproteomics approach for which a robust protein extraction protocol was combined with advanced mass spectrometry. The results identified over 1600 protein groups belonging to all strains present in the VSL#3 formulation. Of interest, only 3.2 % proteins showed significant differences mainly related to small variations in strain abundance. The protocols developed in this study addressed several quality criteria that are relevant for marketed multi-strain products and these represent the first efforts to define the quality of complex probiotic formulations such as VSL#3.}, }
@article {pmid31402174, year = {2019}, author = {Sberro, H and Fremin, BJ and Zlitni, S and Edfors, F and Greenfield, N and Snyder, MP and Pavlopoulos, GA and Kyrpides, NC and Bhatt, AS}, title = {Large-Scale Analyses of Human Microbiomes Reveal Thousands of Small, Novel Genes.}, journal = {Cell}, volume = {178}, number = {5}, pages = {1245-1259.e14}, doi = {10.1016/j.cell.2019.07.016}, pmid = {31402174}, issn = {1097-4172}, abstract = {Small proteins are traditionally overlooked due to computational and experimental difficulties in detecting them. To systematically identify small proteins, we carried out a comparative genomics study on 1,773 human-associated metagenomes from four different body sites. We describe >4,000 conserved protein families, the majority of which are novel; ∼30% of these protein families are predicted to be secreted or transmembrane. Over 90% of the small protein families have no known domain and almost half are not represented in reference genomes. We identify putative housekeeping, mammalian-specific, defense-related, and protein families that are likely to be horizontally transferred. We provide evidence of transcription and translation for a subset of these families. Our study suggests that small proteins are highly abundant and those of the human microbiome, in particular, may perform diverse functions that have not been previously reported.}, }
@article {pmid31396188, year = {2019}, author = {Hietala, V and Horsma-Heikkinen, J and Carron, A and Skurnik, M and Kiljunen, S}, title = {The Removal of Endo- and Enterotoxins From Bacteriophage Preparations.}, journal = {Frontiers in microbiology}, volume = {10}, number = {}, pages = {1674}, doi = {10.3389/fmicb.2019.01674}, pmid = {31396188}, issn = {1664-302X}, abstract = {The production of phages for therapeutic purposes demands fast, efficient and scalable purification procedures. Phage lysates have a wide range of impurities, of which endotoxins of gram-negative bacteria and protein toxins produced by many pathogenic bacterial species are harmful to humans. The highest allowed endotoxin concentration for parenterally applied medicines is 5 EU/kg/h. The aim of this study was to evaluate the feasibility of different purification methods in endotoxin and protein toxin removal in the production of phage preparations for clinical use. In the purification assays, we utilized three phages: Escherichia phage vB_EcoM_fHoEco02, Acinetobacter phage vB_ApiM_fHyAci03, and Staphylococcus phage vB_SauM_fRuSau02. The purification methods tested in the study were precipitation with polyethylene glycol, ultracentrifugation, ultrafiltration, anion exchange chromatography, octanol extraction, two different endotoxin removal columns, and different combinations thereof. The efficiency of the applied purification protocols was evaluated by measuring phage titer and either endotoxins or staphylococcal enterotoxins A and C (SEA and SEC, respectively) from samples taken from different purification steps. The most efficient procedure in endotoxin removal was the combination of ultrafiltration and EndoTrap HD affinity column, which was able to reduce the endotoxin-to-phage ratio of vB_EcoM_fHoEco02 lysate from 3.5 × 104 Endotoxin Units (EU)/109 plaque forming units (PFU) to 0.09 EU/109 PFU. The combination of ultrafiltration and anion exchange chromatography resulted in ratio 96 EU/109 PFU, and the addition of octanol extraction step into this procedure still reduced this ratio threefold. The other methods tested either resulted to less efficient endotoxin removal or required the use of harmful chemicals that should be avoided when producing phage preparations for medical use. Ultrafiltration with 100,000 MWCO efficiently removed enterotoxins from vB_SauM_fRuSau02 lysate (from 1.3 to 0.06 ng SEA/109 PFU), and anion exchange chromatography reduced the enterotoxin concentration below 0.25 ng/ml, the detection limit of the assay.}, }
@article {pmid31388693, year = {2019}, author = {Stoyancheva, G}, title = {Study of helveticin gene in Lactobacillus crispatus strains and evaluation of its use as a phylogenetic marker.}, journal = {Archives of microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1007/s00203-019-01711-2}, pmid = {31388693}, issn = {1432-072X}, abstract = {Lactobacilli are a part of the human microbiome in healthy humans. Studies of their physiological and genetic characteristics are the basis for their use in probiotic preparations. This report is a brief description of the helveticin gene found in two Lactobacillus crispatus strains, which are a part of the human microbiome. Our analysis showed that the two variants of the gene are not solely characteristic of strains isolated from humans. In the phylogenetic analysis, we found that the studied sequence (this gene) showed a significant difference between the species of the genus Lactobacillus and could be used as a phylogenetic marker.}, }
@article {pmid31387651, year = {2019}, author = {Roura, E and Depoortere, I and Navarro, M}, title = {Review: Chemosensing of nutrients and non-nutrients in the human and porcine gastrointestinal tract.}, journal = {Animal : an international journal of animal bioscience}, volume = {}, number = {}, pages = {1-13}, doi = {10.1017/S1751731119001794}, pmid = {31387651}, issn = {1751-732X}, abstract = {The gastrointestinal tract (GIT) is an interface between the external and internal milieus that requires continuous monitoring for nutrients or pathogens and toxic chemicals. The study of the physiological/molecular mechanisms, mediating the responses to the monitoring of the GIT contents, has been referred to as chemosensory science. While most of the progress in this area of research has been obtained in laboratory rodents and humans, significant steps forward have also been reported in pigs. The objective of this review was to update the current knowledge on nutrient chemosensing in pigs in light of recent advances in humans and laboratory rodents. A second objective relates to informing the existence of nutrient sensors with their functionality, particularly linked to the gut peptides relevant to the onset/offset of appetite. Several cell types of the intestinal epithelium such as Paneth, goblet, tuft and enteroendocrine cells (EECs) contain subsets of chemosensory receptors also found on the tongue as part of the taste system. In particular, EECs show specific co-expression patterns between nutrient sensors and/or transceptors (transport proteins with sensing functions) and anorexigenic hormones such as cholecystokinin (CCK), peptide tyrosine tyrosine (PYY) or glucagon-like peptide-1 (GLP-1), amongst others. In addition, the administration of bitter compounds has an inhibitory effect on GIT motility and on appetite through GLP-1-, CCK-, ghrelin- and PYY-labelled EECs in the human small intestine and colon. Furthermore, the mammalian chemosensory system is the target of some bacterial metabolites. Recent studies on the human microbiome have discovered that commensal bacteria have developed strategies to stimulate chemosensory receptors and trigger host cellular functions. Finally, the study of gene polymorphisms related to nutrient sensors explains differences in food choices, food intake and appetite between individuals.}, }
@article {pmid31383276, year = {2019}, author = {Chu, DM and Valentine, GC and Seferovic, MD and Aagaard, KM}, title = {The Development of the Human Microbiome: Why Moms Matter.}, journal = {Gastroenterology clinics of North America}, volume = {48}, number = {3}, pages = {357-375}, doi = {10.1016/j.gtc.2019.04.004}, pmid = {31383276}, issn = {1558-1942}, support = {R01 DK089201/DK/NIDDK NIH HHS/United States ; R01 HD091731/HD/NICHD NIH HHS/United States ; }, abstract = {The human body is cohabitated with trillions of commensal bacteria that are essential for our health. However, certain bacteria can also cause diseases in the human host. Before the microbiome can be attributed to disease risk and pathogenesis, normal acquisition and development of the microbiome must be understood. Here, we explore the evidence surrounding in utero microbial exposures and the significant of this exposure in the proper development of the fetal and neonatal microbiome. We further explore the development of the fetal and neonatal microbiome and its relationship to preterm birth, feeding practices, and mode of delivery, and maternal diet.}, }
@article {pmid31379797, year = {2019}, author = {Lo Presti, A and Zorzi, F and Del Chierico, F and Altomare, A and Cocca, S and Avola, A and De Biasio, F and Russo, A and Cella, E and Reddel, S and Calabrese, E and Biancone, L and Monteleone, G and Cicala, M and Angeletti, S and Ciccozzi, M and Putignani, L and Guarino, MPL}, title = {Fecal and Mucosal Microbiota Profiling in Irritable Bowel Syndrome and Inflammatory Bowel Disease.}, journal = {Frontiers in microbiology}, volume = {10}, number = {}, pages = {1655}, doi = {10.3389/fmicb.2019.01655}, pmid = {31379797}, issn = {1664-302X}, abstract = {An imbalance in the bacterial species resulting in the loss of intestinal homeostasis has been described in inflammatory bowel diseases (IBD) and irritable bowel syndrome (IBS). In this prospective study, we investigated whether IBD and IBS patients exhibit specific changes in richness and distribution of fecal and mucosal-associated microbiota. Additionally, we assessed potential 16S rRNA gene amplicons biomarkers for IBD, IBS, and controls (CTRLs) by comparison of taxonomic composition. The relative abundance of bacteria, at phylum and genus/species levels, and the bacterial diversity were determined through 16S rRNA sequence-based fecal and mucosal microbiota analysis. Linear discriminant analysis effect size (LEfSe) was used for biomarker discovery associated to IBD and IBS as compared to CTRLs. In fecal and mucosal samples, the microbiota richness was characterized by a microbial diversity reduction, going from CTRLs to IBS to IBD. β-diversity analysis showed a clear separation between IBD and CTRLs and between IBD and IBS with no significant separation between IBS and CTRLs. β-diversity showed a clear separation between mucosa and stool samples in all the groups. In IBD, there was no difference between inflamed and not inflamed mucosa. Based upon the LEfSe data, the Anaerostipes and Ruminococcaceae were identified as the most differentially abundant bacterial taxa in CTRLs. Erysipelotrichi was identified as potential biomarker for IBS, while Gammaproteobacteria, Enterococcus, and Enterococcaceae for IBD. This study provides an overview of the alterations of microbiota and may aid in identifying potential 16S rRNA gene amplicons mucosal biomarkers for IBD and IBS.}, }
@article {pmid31378678, year = {2019}, author = {Colosimo, DA and Kohn, JA and Luo, PM and Piscotta, FJ and Han, SM and Pickard, AJ and Rao, A and Cross, JR and Cohen, LJ and Brady, SF}, title = {Mapping Interactions of Microbial Metabolites with Human G-Protein-Coupled Receptors.}, journal = {Cell host &amp; microbe}, volume = {26}, number = {2}, pages = {273-282.e7}, doi = {10.1016/j.chom.2019.07.002}, pmid = {31378678}, issn = {1934-6069}, support = {R01 AT009562/AT/NCCIH NIH HHS/United States ; }, abstract = {Despite evidence linking the human microbiome to health and disease, how the microbiota affects human physiology remains largely unknown. Microbiota-encoded metabolites are expected to play an integral role in human health. Therefore, assigning function to these metabolites is critical to understanding these complex interactions and developing microbiota-inspired therapies. Here, we use large-scale functional screening of molecules produced by individual members of a simplified human microbiota to identify bacterial metabolites that agonize G-protein-coupled receptors (GPCRs). Multiple metabolites, including phenylpropanoic acid, cadaverine, 9-10-methylenehexadecanoic acid, and 12-methyltetradecanoic acid, were found to interact with GPCRs associated with diverse functions within the nervous and immune systems, among others. Collectively, these metabolite-receptor pairs indicate that diverse aspects of human health are potentially modulated by structurally simple metabolites arising from primary bacterial metabolism.}, }
@article {pmid31370220, year = {2019}, author = {Vitetta, L and Llewellyn, H and Oldfield, D}, title = {Gut Dysbiosis and the Intestinal Microbiome: Streptococcus thermophilus a Key Probiotic for Reducing Uremia.}, journal = {Microorganisms}, volume = {7}, number = {8}, pages = {}, doi = {10.3390/microorganisms7080228}, pmid = {31370220}, issn = {2076-2607}, abstract = {In the intestines, probiotics can produce antagonistic effects such as antibiotic-like compounds, bactericidal proteins such as bacteriocins, and encourage the production of metabolic end products that may assist in preventing infections from various pathobionts (capable of pathogenic activity) microbes. Metabolites produced by intestinal bacteria and the adoptions of molecular methods to cross-examine and describe the human microbiome have refreshed interest in the discipline of nephology. As such, the adjunctive administration of probiotics for the treatment of chronic kidney disease (CKD) posits that certain probiotic bacteria can reduce the intestinal burden of uremic toxins. Uremic toxins eventuate from the over manifestation of glucotoxicity and lipotoxicity, increased activity of the hexosamine and polyol biochemical and synthetic pathways. The accumulation of advanced glycation end products that have been regularly associated with a dysbiotic colonic microbiome drives the overproduction of uremic toxins in the colon and the consequent local pro-inflammatory processes. Intestinal dysbiosis associated with significant shifts in abundance and diversity of intestinal bacteria with a resultant and maintained uremia promoting an uncontrolled mucosal pro-inflammatory state. In this narrative review we further address the efficacy of probiotics and highlighted in part the probiotic bacterium Streptococcus thermophilus as an important modulator of uremic toxins in the gut of patients diagnosed with chronic kidney disease. In conjunction with prudent nutritional practices it may be possible to prevent the progression of CKD and significantly downregulate mucosal pro-inflammatory activity with the administration of probiotics that contain S. thermophilus.}, }
@article {pmid31367386, year = {2019}, author = {Fall, NS and Lo, CI and Fournier, PE and Sokhna, C and Raoult, D and Fenollar, F and Lagier, JC}, title = {Arcanobacterium ihumii sp. nov., Varibaculum vaginae sp. nov. and Tessaracoccus timonensis sp. nov., isolated from vaginal swabs from healthy Senegalese women.}, journal = {New microbes and new infections}, volume = {31}, number = {}, pages = {100585}, doi = {10.1016/j.nmni.2019.100585}, pmid = {31367386}, issn = {2052-2975}, abstract = {Culturomics studies the microbial variety of the human microbiome by combining diversified culture conditions, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and 16S rRNA gene identification. This study identifies three putative new bacterial species: Arcanobacterium ihumii sp. nov. strain Marseille-P5647T, Varibaculum vaginae sp. nov. strain Marseille-P5644T and Tessaracoccus timonensis sp. nov. strain Marseille-P5995T, which we describe according to the concept of taxonogenomics.}, }
@article {pmid31354638, year = {2019}, author = {Yin, G and Xia, Y}, title = {Assessing the Hybrid Effects of Neutral and Niche Processes on Gut Microbiome Influenced by HIV Infection.}, journal = {Frontiers in microbiology}, volume = {10}, number = {}, pages = {1467}, doi = {10.3389/fmicb.2019.01467}, pmid = {31354638}, issn = {1664-302X}, abstract = {That both stochastic neutral and deterministic niche forces are in effect in shaping the community assembly and diversity maintenance is becoming an increasingly important consensus. However, assessing the effects of disease on the balance between the two forces in the human microbiome has not been explored to the best of our knowledge. In this article, we applied a hybrid model to address this issue by analyzing the potential effect of HIV infection on the human gut microbiome and adopted a further step of multimodality testing to improve the interpretation of their model. Our study revealed that although niche process is the dominant force in shaping human gut microbial communities, niche process- and neutral process-driven taxa could coexist in the same microbiome, confirming the notion of their joint responsibility. However, we failed to detect the effect of HIV infection in changing the balance. This suggests that the rule governing community assembly and diversity maintenance may be changed by the disturbance from HIV infection-caused dysbiosis. Although we admit that the general question of disease effect on community assembly and diversity maintenance may still be an open question, our study presents the first piece of evidence to reject the significant influence of diseases.}, }
@article {pmid31339096, year = {2019}, author = {Pietilä, JP and Meri, T and Siikamäki, H and Tyyni, E and Kerttula, AM and Pakarinen, L and Jokiranta, TS and Kantele, A}, title = {Dientamoeba fragilis - the most common intestinal protozoan in the Helsinki Metropolitan Area, Finland, 2007 to 2017.}, journal = {Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin}, volume = {24}, number = {29}, pages = {}, doi = {10.2807/1560-7917.ES.2019.24.29.1800546}, pmid = {31339096}, issn = {1560-7917}, abstract = {BackgroundDespite the global distribution of the intestinal protozoan Dientamoeba fragilis, its clinical picture remains unclear. This results from underdiagnosis: microscopic screening methods either lack sensitivity (wet preparation) or fail to reveal Dientamoeba (formalin-fixed sample).AimIn a retrospective study setting, we characterised the clinical picture of dientamoebiasis and compared it with giardiasis. In addition, we evaluated an improved approach to formalin-fixed samples for suitability in Dientamoeba diagnostics.MethodsThis study comprised four parts: (i) a descriptive part scrutinising rates of Dientamoeba findings; (ii) a methodological part analysing an approach to detect Dientamoeba-like structures in formalin samples; (iii) a clinical part comparing demographics and symptoms between patients with dientamoebiasis (n = 352) and giardiasis (n = 272), and (iv) a therapeutic part (n = 89 patients) investigating correlation between faecal eradication and clinical improvement.ResultsThe rate of Dientamoeba findings increased 20-fold after introducing criteria for Dientamoeba-like structures in formalin-fixed samples (88.9% sensitivity and 83.3% specificity). A further increase was seen after implementing faecal PCR. Compared with patients with giardiasis, the symptoms in the Dientamoeba group lasted longer and more often included abdominal pain, cramping, faecal urgency and loose rather than watery stools. Resolved symptoms correlated with successful faecal eradication (p < 0.001).ConclusionsPreviously underdiagnosed, Dientamoeba has become the most frequently recorded pathogenic enteroparasite in Finland. This presumably results from improved diagnostics with either PCR or detection of Dientamoeba-like structures in formalin-fixed samples, an approach applicable also in resource-poor settings. Symptoms of dientamoebiasis differ slightly from those of giardiasis; patients with distressing symptoms require treatment.}, }
@article {pmid31338330, year = {2019}, author = {Dong, Z and Chen, B and Pan, H and Wang, D and Liu, M and Yang, Y and Zou, M and Yang, J and Xiao, K and Zhao, R and Zheng, X and Zhang, L and Zhang, Y}, title = {Detection of Microbial 16S rRNA Gene in the Serum of Patients With Gastric Cancer.}, journal = {Frontiers in oncology}, volume = {9}, number = {}, pages = {608}, doi = {10.3389/fonc.2019.00608}, pmid = {31338330}, issn = {2234-943X}, abstract = {Aberrance in the blood bacterial microbiome has been identified and validated in several non-infectious diseases, including cancer. The occurrence and progression of gastric cancer has been found to be associated with alterations in the microbiome composition. However, the composition of the blood microbiome in patients with gastric cancer is not well-characterized. To test this hypothesis, we conducted a case-control study to investigate the microbiota compositions in the serum of patients with gastric cancer. The serum microbiome was investigated in patients with gastric cancer, atypical hyperplasia, chronic gastritis, and in healthy controls using 16S rRNA gene sequencing targeting the V1-V2 region. Our results revealed that the structure of the serum microbiome in gastric cancer was significantly different from all other groups, and alpha diversity decreased from the healthy control to patients with gastric cancer. The serum microbiome correlated significantly with tumor-node-metastasis (TNM) stage, lymphatic metastasis, tumor diameter, and invasion depth in gastric cancer. Three genera or species, namely, Acinetobacter, Bacteroides, Haemophilus parainfluenzae, were enriched in patients with gastric cancer, whereas Sphingomonas, Comamonas, and Pseudomonas stutzeri were enriched in the healthy control. Furthermore, the structure of serum microbiota differed between gastric cancer lymphatic metastasis and non-lymphatic metastasis. As a pilot investigation to characterizing the serum microbiome in gastric cancer, our study provided a foundation for improving our understanding of the role of microbiota in the pathogenesis of gastric cancer.}, }
@article {pmid31337891, year = {2019}, author = {Kumar, M and Ji, B and Zengler, K and Nielsen, J}, title = {Modelling approaches for studying the microbiome.}, journal = {Nature microbiology}, volume = {4}, number = {8}, pages = {1253-1267}, doi = {10.1038/s41564-019-0491-9}, pmid = {31337891}, issn = {2058-5276}, abstract = {Advances in metagenome sequencing of the human microbiome have provided a plethora of new insights and revealed a close association of this complex ecosystem with a range of human diseases. However, there is little knowledge about how the different members of the microbial community interact with each other and with the host, and we lack basic mechanistic understanding of these interactions related to health and disease. Mathematical modelling has been demonstrated to be highly advantageous for gaining insights into the dynamics and interactions of complex systems and in recent years, several modelling approaches have been proposed to enhance our understanding of the microbiome. Here, we review the latest developments and current approaches, and highlight how different modelling strategies have been applied to unravel the highly dynamic nature of the human microbiome. Furthermore, we discuss present limitations of different modelling strategies and provide a perspective of how modelling can advance understanding and offer new treatment routes to impact human health.}, }
@article {pmid31337077, year = {2019}, author = {Scribano, D and Marzano, V and Levi Mortera, S and Sarshar, M and Vernocchi, P and Zagaglia, C and Putignani, L and Palamara, AT and Ambrosi, C}, title = {Insights into the Periplasmic Proteins of Acinetobacter baumannii AB5075 and the Impact of Imipenem Exposure: A Proteomic Approach.}, journal = {International journal of molecular sciences}, volume = {20}, number = {14}, pages = {}, doi = {10.3390/ijms20143451}, pmid = {31337077}, issn = {1422-0067}, abstract = {Carbapenem-resistant Acinetobacter baumannii strains cause life-threatening infections due to the lack of therapeutic options. Although the main mechanisms underlying antibiotic-resistance have been extensively studied, the general response to maintain bacterial viability under antibiotic exposure deserves to be fully investigated. Since the periplasmic space contains several proteins with crucial cellular functions, besides carbapenemases, we decided to study the periplasmic proteome of the multidrug-resistant (MDR) A. baumannii AB5075 strain, grown in the absence and presence of imipenem (IMP). Through the proteomic approach, 65 unique periplasmic proteins common in both growth conditions were identified: eight proteins involved in protein fate, response to oxidative stress, energy metabolism, antibiotic-resistance, were differentially expressed. Among them, ABUW_1746 and ABUW_2363 gene products presented the tetratricopeptide repeat motif, mediating protein-protein interactions. The expression switch of these proteins might determine specific protein interactions to better adapt to changing environmental conditions. ABUW_2868, encoding a heat shock protein likely involved in protection against oxidative stress, was upregulated in IMP-exposed bacteria. Accordingly, the addition of periplasmic proteins from A. baumannii cultured with IMP increased bacterial viability in an antioxidant activity assay. Overall, this study provides the first insights about the composition of the periplasmic proteins of a MDR A. baumannii strain, its biological response to IMP and suggests possible new targets to develop alternative antibiotic drugs.}, }
@article {pmid31337018, year = {2019}, author = {Wakabayashi, R and Nakahama, Y and Nguyen, V and Espinoza, JL}, title = {The Host-Microbe Interplay in Human Papillomavirus-Induced Carcinogenesis.}, journal = {Microorganisms}, volume = {7}, number = {7}, pages = {}, doi = {10.3390/microorganisms7070199}, pmid = {31337018}, issn = {2076-2607}, abstract = {Every year nearly half a million new cases of cervix cancer are diagnosed worldwide, making this malignancy the fourth commonest cancer in women. In 2018, more than 270,000 women died of cervix cancer globally with 85% of them being from developing countries. The majority of these cancers are caused by the infection with carcinogenic strains of human papillomavirus (HPV), which is also causally implicated in the development of other malignancies, including cancer of the anus, penis cancer and head and neck cancer. HPV is by far the most common sexually transmitted infection worldwide, however, most infected people do not develop cancer and do not even have a persistent infection. The development of highly effective HPV vaccines against most common high-risk HPV strains is a great medical achievement of the 21st century that could prevent up to 90% of cervix cancers. In this article, we review the current understanding of the balanced virus-host interaction that can lead to either virus elimination or the establishment of persistent infection and ultimately malignant transformation. We also highlight the influence of certain factors inherent to the host, including the immune status, genetic variants and the coexistence of other microbe infections and microbiome composition in the dynamic of HPV infection induced carcinogenesis.}, }
@article {pmid31336807, year = {2019}, author = {Hamidi, B and Wallace, K and Alekseyenko, AV}, title = {MODIMA, a Method for Multivariate Omnibus Distance Mediation Analysis, Allows for Integration of Multivariate Exposure-Mediator-Response Relationships.}, journal = {Genes}, volume = {10}, number = {7}, pages = {}, doi = {10.3390/genes10070524}, pmid = {31336807}, issn = {2073-4425}, support = {R21 TR002513/NCATS NIH HHS/National Center for Advancing Translational Sciences/United States ; U54 CA210962/NCI NIH HHS/National Cancer Institute/United States ; UL1 TR001450/NCATS NIH HHS/National Center for Advancing Translational Sciences/United States ; }, abstract = {Many important exposure-response relationships, such as diet and weight, can be influenced by intermediates, such as the gut microbiome. Understanding the role of these intermediates, the mediators, is important in refining cause-effect theories and discovering additional medical interventions (e.g., probiotics, prebiotics). Mediation analysis has been at the heart of behavioral health research, rapidly gaining popularity with the biomedical sciences in the last decade. A specific analytic challenge is being able to incorporate an entire 'omics assay as a mediator. To address this challenge, we propose a hypothesis testing framework for multivariate omnibus distance mediation analysis (MODIMA). We use the power of energy statistics, such as partial distance correlation, to allow for analysis of multivariate exposure-mediator-response triples. Our simulation results demonstrate the favorable statistical properties of our approach relative to the available alternatives. Finally, we demonstrate the application of the proposed methods in two previously published microbiome datasets. Our framework adds a new tool to the toolbox of approaches to the integration of 'omics big data.}, }
@article {pmid31328778, year = {2019}, author = {PeBenito, AM and Liu, M and Nazzal, L and Blaser, MJ}, title = {Development of a humanized murine model for the study of Oxalobacter formigenes intestinal colonization.}, journal = {The Journal of infectious diseases}, volume = {}, number = {}, pages = {}, doi = {10.1093/infdis/jiz370}, pmid = {31328778}, issn = {1537-6613}, abstract = {BACKGROUND: Oxalobacter formigenes are bacteria that colonize the human gut and degrade oxalate, a component of most kidney stones. Clinical and epidemiological studies suggest that O. formigenes colonization reduces the risk for kidney stones. We sought to develop murine models to allow investigating O. formigenes in the context of its native human microbiome.For humanization, we transplanted pooled feces from healthy, non-colonized human donors supplemented with a human O. formigenes strain into recipient mice. We compared transplanting microbiota into mice that were either treated with broad-spectrum antibiotics to suppress their native microbiome, or were germ-free, or received humanization without pre-treatment or received a sham gavage (controls).<br><br>RESULTS: All humanized mice were stably colonized with O. formigenes through 8 weeks post-gavage, whereas mice receiving sham gavage remained uncolonized (p<0.001). Humanization significantly changed the murine intestinal microbial community structure (p<0.001) with humanized germ-free and antibiotic-treated groups overlapping in β-diversity. Both the germ-free and antibiotic-treated mice had significantly increased numbers of human species compared to sham-gavaged mice (p<0.001).<br><br>CONCLUSIONS: Transplanting mice with human feces and O. formigenes introduced new microbial populations resembling the human microbiome, with stable O. formigenes colonization; such models can define optimal O. formigenes strains to facilitate clinical trials.}, }
@article {pmid31327398, year = {2019}, author = {O'Gorman, DB and Pena-Diaz, AM and Drosdowech, D and Faber, KJ and Athwal, GS and Burton, JP and Al, K and Huang, T and Qiu, B}, title = {Response to Long et al regarding: &quot;Cutibacterium acnes and the shoulder microbiome&quot;.}, journal = {Journal of shoulder and elbow surgery}, volume = {28}, number = {8}, pages = {e277-e278}, doi = {10.1016/j.jse.2019.04.047}, pmid = {31327398}, issn = {1532-6500}, }
@article {pmid31323792, year = {2019}, author = {Santiago-Rodriguez, TM and Hollister, EB}, title = {Human Virome and Disease: High-Throughput Sequencing for Virus Discovery, Identification of Phage-Bacteria Dysbiosis and Development of Therapeutic Approaches with Emphasis on the Human Gut.}, journal = {Viruses}, volume = {11}, number = {7}, pages = {}, doi = {10.3390/v11070656}, pmid = {31323792}, issn = {1999-4915}, abstract = {The virome is comprised of endogenous retroviruses, eukaryotic viruses, and bacteriophages and is increasingly being recognized as an essential part of the human microbiome. The human virome is associated with Type-1 diabetes (T1D), Type-2 diabetes (T2D), Inflammatory Bowel Disease (IBD), Human Immunodeficiency Virus (HIV) infection, and cancer. Increasing evidence also supports trans-kingdom interactions of viruses with bacteria, small eukaryotes and host in disease progression. The present review focuses on virus ecology and biology and how this translates mostly to human gut virome research. Current challenges in the field and how the development of bioinformatic tools and controls are aiding to overcome some of these challenges are also discussed. Finally, the present review also focuses on how human gut virome research could result in translational and clinical studies that may facilitate the development of therapeutic approaches.}, }
@article {pmid31322866, year = {2019}, author = {Huddleston, JP and Thoden, JB and Dopkins, BJ and Narindoshvili, T and Fose, BJ and Holden, HM and Raushel, FM}, title = {Structural and Functional Characterization of YdjI, an Aldolase of Unknown Specificity in Escherichia coli K12.}, journal = {Biochemistry}, volume = {58}, number = {31}, pages = {3340-3353}, doi = {10.1021/acs.biochem.9b00326}, pmid = {31322866}, issn = {1520-4995}, support = {R01 GM115921/NIGMS NIH HHS/National Institute of General Medical Sciences/United States ; }, abstract = {The ydj gene cluster is found in 80% of sequenced Escherichia coli genomes and other closely related species in the human microbiome. On the basis of the annotations of the enzymes located in this cluster, it is expected that together they catalyze the catabolism of an unknown carbohydrate. The focus of this investigation is on YdjI, which is in the ydj gene cluster of E. coli K-12. It is predicted to be a class II aldolase of unknown function. Here we describe a structural and functional characterization of this enzyme. YdjI catalyzes the hydrogen/deuterium exchange of the pro-S hydrogen at C3 of dihydroxyacetone phosphate (DHAP). In the presence of DHAP, YdjI catalyzes an aldol condensation with a variety of aldo sugars. YdjI shows a strong preference for higher-order (seven-, eight-, and nine-carbon) monosaccharides with specific hydroxyl stereochemistries and a negatively charged terminus (carboxylate or phosphate). The best substrate is l-arabinuronic acid with an apparent kcat of 3.0 s-1. The product, l-glycero-l-galacto-octuluronate-1-phosphate, has a kcat/Km value of 2.1 × 103 M-1 s-1 in the retro-aldol reaction with YdjI. This is the first recorded synthesis of l-glycero-l-galacto-octuluronate-1-phosphate and six similar carbohydrates. The crystal structure of YdjI, determined to a nominal resolution of 1.75 Å (Protein Data Bank entry 6OFU), reveals unusual positions for two arginine residues located near the active site. Computational docking was utilized to distinguish preferable binding orientations for l-glycero-l-galacto-octuluronate-1-phosphate. These results indicate a possible alternative binding orientation for l-glycero-l-galacto-octuluronate-1-phosphate compared to that observed in other class II aldolases, which utilize shorter carbohydrate molecules.}, }
@article {pmid31321880, year = {2019}, author = {Peters, DL and Wang, W and Zhang, X and Ning, Z and Mayne, J and Figeys, D}, title = {Metaproteomic and Metabolomic Approaches for Characterizing the Gut Microbiome.}, journal = {Proteomics}, volume = {19}, number = {16}, pages = {e1800363}, doi = {10.1002/pmic.201800363}, pmid = {31321880}, issn = {1615-9861}, support = {NSERC-CREATE TECHNOMISE//Natural Sciences and Engineering Research Council of Canada/ ; OGI-114//Genome Canada/ ; OGI-149//Genome Canada/ ; OGI-156//Genome Canada/ ; GPH-129340/CAPMC/CIHR/Canada ; MOP-114872/CAPMC/CIHR/Canada ; }, abstract = {The gut microbiome has been shown to play a significant role in human healthy and diseased states. The dynamic signaling that occurs between the host and microbiome is critical for the maintenance of host homeostasis. Analyzing the human microbiome with metaproteomics, metabolomics, and integrative multi-omics analyses can provide significant information on markers for healthy and diseased states, allowing for the eventual creation of microbiome-targeted treatments for diseases associated with dysbiosis. Metaproteomics enables functional activity information to be gained from the microbiome samples, while metabolomics provides insight into the overall metabolic states affecting/representing the host-microbiome interactions. Combining these functional -omic platforms together with microbiome composition profiling allows for a holistic overview on the functional and metabolic state of the microbiome and its influence on human health. Here the benefits of metaproteomics, metabolomics, and the integrative multi-omic approaches to investigating the gut microbiome in the context of human health and diseases are reviewed.}, }
@article {pmid31319564, year = {2019}, author = {Ticinesi, A and Nouvenne, A and Cerundolo, N and Catania, P and Prati, B and Tana, C and Meschi, T}, title = {Gut Microbiota, Muscle Mass and Function in Aging: A Focus on Physical Frailty and Sarcopenia.}, journal = {Nutrients}, volume = {11}, number = {7}, pages = {}, doi = {10.3390/nu11071633}, pmid = {31319564}, issn = {2072-6643}, abstract = {Human gut microbiota is able to influence the host physiology by regulating multiple processes, including nutrient absorption, inflammation, oxidative stress, immune function, and anabolic balance. Aging is associated with reduced microbiota biodiversity, increased inter-individual variability, and over-representation of pathobionts, and these phenomena may have great relevance for skeletal muscle mass and function. For this reason, the presence of a gut-muscle axis regulating the onset and progression of age-related physical frailty and sarcopenia has been recently hypothesized. In this narrative review, we summarize the studies supporting a possible association between gut microbiota-related parameters with measures of muscle mass, muscle function, and physical performance in animal models and humans. Reduced muscle mass has been associated with distinct microbiota composition and reduced fermentative capacity in mice, and the administration of probiotics or butyrate to mouse models of muscle wasting has been associated with improved muscle mass. However, no studies have targeted the human microbiome associated with sarcopenia. Limited evidence from human studies shows an association between microbiota composition, involving key taxa such as Faecalibacterium and Bifidobacterium, and grip strength. Similarly, few studies conducted on patients with parkinsonism showed a trend towards a different microbiota composition in those with reduced gait speed. No studies have assessed the association of fecal microbiota with other measures of physical performance. However, several studies, mainly with a cross-sectional design, suggest an association between microbiota composition and frailty, mostly assessed according to the deficit accumulation model. Namely, frailty was associated with reduced microbiota biodiversity, and lower representation of butyrate-producing bacteria. Therefore, we conclude that the causal link between microbiota and physical fitness is still uncertain due to the lack of targeted studies and the influence of a large number of covariates, including diet, exercise, multimorbidity, and polypharmacy, on both microbiota composition and physical function in older age. However, the relationship between gut microbiota and physical function remains a very promising area of research for the future.}, }
@article {pmid31316375, year = {2019}, author = {Novotný, M and Klimova, B and Valis, M}, title = {Microbiome and Cognitive Impairment: Can Any Diets Influence Learning Processes in a Positive Way?.}, journal = {Frontiers in aging neuroscience}, volume = {11}, number = {}, pages = {170}, doi = {10.3389/fnagi.2019.00170}, pmid = {31316375}, issn = {1663-4365}, abstract = {The aim of this review is to summarize the effect of human intestinal microbiome on cognitive impairments and to focus primarily on the impact of diet and eating habits on learning processes. Better understanding of the microbiome could revolutionize the possibilities of therapy for many diseases. The authors performed a literature review of available studies on the research topic describing the influence of human microbiome and diet on cognitive impairment or learning processes found in the world's acknowledged databases Web of Science, PubMed, Springer, and Scopus. The digestive tube is populated by billions of living microorganisms including viruses, bacteria, protozoa, helminths, and microscopic fungi. In adulthood, under physiological conditions, the intestinal microbiome appears to be relatively steady. However, it is not true that it would not be influenced, both in the positive sense of the word and in the negative one. The basic pillars that maintain a steady microbiome are genetics, lifestyle, diet and eating habits, geography, and age. It is reported that the gastrointestinal tract and the brain communicate with each other through several pathways and one can speak about gut-brain axis. New evidence is published every year about the association of intestinal dysbiosis and neurological/psychiatric diseases. On the other hand, specific diets and eating habits can have a positive effect on a balanced microbiota composition and thus contribute to the enhancement of cognitive functions, which are important for any learning process.}, }
@article {pmid31315786, year = {2019}, author = {Zhou, H and Suo, J and Zhu, J}, title = {[Therapeutic Relevance of Human Microbiota and Lung Cancer].}, journal = {Zhongguo fei ai za zhi = Chinese journal of lung cancer}, volume = {22}, number = {7}, pages = {464-469}, doi = {10.3779/j.issn.1009-3419.2019.07.09}, pmid = {31315786}, issn = {1999-6187}, abstract = {The human microbiome is closely related to human health status. Disruption of the symbiotic balance of the human microbiome is commonly found in systematic diseases such as diabetes, obesity, and chronic gastric diseases. The human microbiome confers benefits or disease susceptibility to the human body through multiple pathways, associated with approximately 20% of malignancies. The incidence and mortality of lung cancer (LC) in men in China are the highest among all malignancies, which is a serious threat to human health. Emerging evidence has suggested that the human microbiota may be closely related to lung cancer at multiple levels, e.g., by affecting metabolic, inflammatory, or immune pathways. At the same time, the human microbiota affects the efficacy of lung cancer on chemoradiotherapy, gene therapy, immunotherapy and other treatments. Immunotherapy is a promising method for the treatment of malignancies such as lung cancer, but the efficacy of immune checkpoint inhibitors in patients is heterogeneous. Preclinical studies based on lung cancer cell lines suggest that the intestinal microbiota can modulate responses to anti--PD-1 therapy through interactions with the host immune system. But for lung cancer patients, whether the intestinal flora can still regulate immunotherapy remains controversial. In this mini-review, we summarize current research findings describing therapeutic relevance of human microbiota and lung cancer. A better knowledge of the interplay between the human microbiome and lung cancer may promote the development of innovative strategies for prevention and personalized treatment in lung cancer.}, }
@article {pmid31312608, year = {2019}, author = {Gallon, P and Parekh, M and Ferrari, S and Fasolo, A and Ponzin, D and Borroni, D}, title = {Metagenomics in ophthalmology: Hypothesis or real prospective?.}, journal = {Biotechnology reports (Amsterdam, Netherlands)}, volume = {23}, number = {}, pages = {e00355}, doi = {10.1016/j.btre.2019.e00355}, pmid = {31312608}, issn = {2215-017X}, abstract = {Metagenomic analysis was originally associated with the studies of genetic material from environmental samples. But, with the advent of the Human Microbiome Project, it has now been applied in clinical practices. The ocular surface (OS) is the most exposed part of the eye, colonized by several microbial communities (both, OS and environmental) that contribute to the maintenance of the physiological state. Limited knowledge has been acquired on these microbes due to the limitations of conventional diagnostic methods. Emerging fields of research are focusing on Next Generation Sequencing (NGS) technologies to obtain reliable information on the OS microbiome. Currently only pre-specified pathogens can be detected by conventional culture-based techniques or Polymerase Chain Reaction (PCR), but there are conditions to state whether metagenomics could revolutionize the diagnosis of ocular diseases. The aim of this review is to provide an updated overview of the studies involving NGS technology for OS microbiome.}, }
@article {pmid31307469, year = {2019}, author = {Huang, C and Shi, G}, title = {Smoking and microbiome in oral, airway, gut and some systemic diseases.}, journal = {Journal of translational medicine}, volume = {17}, number = {1}, pages = {225}, doi = {10.1186/s12967-019-1971-7}, pmid = {31307469}, issn = {1479-5876}, support = {81770025//National Natural Science Foundation of China/ ; }, abstract = {The human microbiome harbors a diverse array of microbes which establishes a mutually beneficial relation with the host in healthy conditions, however, the dynamic homeostasis is influenced by both host and environmental factors. Smoking contributes to modifications of the oral, lung and gut microbiome, leading to various diseases, such as periodontitis, asthma, chronic obstructive pulmonary disease, Crohn's disease, ulcerative colitis and cancers. However, the exact causal relationship between smoking and microbiome alteration remains to be further explored.}, }
@article {pmid31301004, year = {2019}, author = {Li, JKM and Chiu, PKF and Ng, CF}, title = {The impact of microbiome in urological diseases: a systematic review.}, journal = {International urology and nephrology}, volume = {}, number = {}, pages = {}, doi = {10.1007/s11255-019-02225-y}, pmid = {31301004}, issn = {1573-2584}, abstract = {OBJECTIVE: The term microbiome is used to signify the ecological community of commensal, symbiotic, and pathogenic microorganisms that share our body space, in which there were increasing evidences to suggest that they might have potential roles in various medical conditions. While the study of microbiome in the urinary system is not as robust as the systems included in the Human Microbiome Project, there are still evidences in the literature showing that microbiome may have a role in urological diseases. Therefore, we would like to perform a systematic review on the topic and summarize the available evidence on the impact of microbiome on urological diseases.<br><br>METHODOLOGY: This review was performed according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. After screening 589 abstracts and including additional studies (such as references from review papers), 76 studies were included for review and discussion.<br><br>RESULTS: Studies had suggested that there were correlations of microbiome of different body cavities (e.g., fecal, urinary and seminal fluid) with urological diseases. Also, different diseases would have different microbiome profile in different body cavities. Unfortunately, the studies on the association of microbiome and urological diseases were still either weak or inconsistent.<br><br>CONCLUSION: Studies suggested that there might be some relationship between microbiome and various urological diseases. However, further large-scale studies with control of confounding factors should be performed under a standardized methodology in order to have better understanding of the relationship. Also, more standardized reporting protocol for microbiome studies should be considered for better communications in future studies.}, }
@article {pmid31297102, year = {2019}, author = {Zhang, Z and Yang, J and Feng, Q and Chen, B and Li, M and Liang, C and Li, M and Li, Z and Xu, Q and Zhang, L and Chen, W}, title = {Compositional and Functional Analysis of the Microbiome in Tissue and Saliva of Oral Squamous Cell Carcinoma.}, journal = {Frontiers in microbiology}, volume = {10}, number = {}, pages = {1439}, doi = {10.3389/fmicb.2019.01439}, pmid = {31297102}, issn = {1664-302X}, abstract = {Oral squamous cell carcinoma (OSCC) is affected by the interaction between oral pathogen and holobionts, or the combination of the host and its microbial communities. Studies have indicated the structure and feature of the microbiome in OSCC tissue and saliva, the relationships between microbiota and OSCC sites, stages remain unclear. In the present study, OSCC tissue (T), saliva (S) and mouthwash (W) samples were collected from the same subjects and carried out the microbiome study by 16S sequencing. The results showed the T group was significantly different from the S and W groups with the character of lower richness and diversity. Proteobacteria were most enriched in the T group at the phylum level, while Firmicutes were predominant in groups S and W. At the genus level, the predominant taxa of group T were Acinetobacter and Fusobacterium, and for group S and W, the predominant taxa were Streptococcus and Prevotella. The genera related to late stage tumors were Acinetobacter and Fusobacterium, suggesting microbiota may be implicated in OSCC developing. Both compositional and functional analyses indicated that microbes in tumor tissue were potential indicator for the initiation and development of OSCC.}, }
@article {pmid31295421, year = {2019}, author = {Lam, KN and Alexander, M and Turnbaugh, PJ}, title = {Precision Medicine Goes Microscopic: Engineering the Microbiome to Improve Drug Outcomes.}, journal = {Cell host &amp; microbe}, volume = {26}, number = {1}, pages = {22-34}, doi = {10.1016/j.chom.2019.06.011}, pmid = {31295421}, issn = {1934-6069}, support = {R01 HL122593/HL/NHLBI NIH HHS/United States ; R21 CA227232/CA/NCI NIH HHS/United States ; T32 AI060537/AI/NIAID NIH HHS/United States ; }, abstract = {Despite the recognition, nearly a century ago, that the human microbiome plays a clinically relevant role in drug disposition, mechanistic insights, and translational applications are still limited. Here, we highlight the recent re-emergence of &quot;pharmacomicrobiomics,&quot; which seeks to understand how inter-individual variations in the microbiome shape drug efficacy and side effect profiles. Multiple bacterial species, genes, and enzymes have already been implicated in the direct biotransformation of drugs, both from targeted case studies and from systematic computational and experimental analyses. Indirect mechanisms are also at play; for example, microbial interactions with the host immune system can have broad effects on immunomodulatory drugs. Finally, we discuss multiple emerging strategies for the precise manipulation of complex microbial communities to improve treatment outcomes. In the coming years, we anticipate a shift toward a more comprehensive view of precision medicine that encompasses our human and microbial genomes and their combined metabolic activities.}, }
@article {pmid31292231, year = {2019}, author = {Mike, LA}, title = {mSphere of Influence: Systematically Decoding Microbial Chemical Communication.}, journal = {mSphere}, volume = {4}, number = {4}, pages = {}, doi = {10.1128/mSphere.00319-19}, pmid = {31292231}, issn = {2379-5042}, abstract = {Laura A. Mike works in the field of bacterial pathogenesis. In this mSphere of Influence article, she reflects on how &quot;Insights into Secondary Metabolism from a Global Analysis of Prokaryotic Biosynthetic Gene Clusters&quot; by P. Cimermancic et al. (Cell 158:412-421, 2014, https://doi.org/10.1016/j.cell.2014.06.034) and &quot;A Systematic Analysis of Biosynthetic Gene Clusters in the Human Microbiome Reveals a Common Family of Antibiotics&quot; by M. S. Donia et al. (Cell 158:1402-1414, 2014, https://doi.org/10.1016/j.cell.2014.08.032) made an impact on her by systematically identifying microbiome-associated biosynthetic gene clusters predicted to synthesize secondary metabolites, which may facilitate interspecies interactions.}, }
@article {pmid31288283, year = {2019}, author = {Wree, A and Geisler, LJ and Tacke, F}, title = {[Microbiome &amp; NASH - partners in crime driving progression of fatty liver disease].}, journal = {Zeitschrift fur Gastroenterologie}, volume = {57}, number = {7}, pages = {871-882}, doi = {10.1055/a-0755-2595}, pmid = {31288283}, issn = {1439-7803}, abstract = {Along with the increasing prevalence of obesity, metabolic syndrome and type 2 diabetes, non-alcoholic fatty liver disease (NAFLD) is rapidly increasing and poses a major challenge for gastroenterologists. Many studies have demonstrated that the microbiome is closely associated with the progression of nutrition-related diseases, especially of fatty liver disease. Changes in the quantity and quality of the intestinal flora, commonly referred to as dysbiosis, result in altered food metabolism, increased permeability of the intestinal barrier (&quot;leaky gut&quot;) and consecutive inflammatory processes in the liver. This favors both the progression of obesity and metabolic disorders as well as NAFLD towards non-alcoholic steatohepatitis (NASH), hepatic fibrosis, cirrhosis and hepatocellular carcinoma (HCC). Important molecular mechanisms include microbial metabolites, microbial and endogenous signaling substances (so-called PAMPs/DAMPs) as well as bile acids. Essential cellular mechanisms include immune cells in the gut and liver, especially macrophages and Kupffer cells, as well as intestinal epithelial cells and hepatocytes as central regulators of metabolism. In this review article, we briefly summarize the relevant species of the human microbiome, describe the microbial analytics, explain the most important molecular relationships between microbiome and NAFLD/NASH, and finally the opportunities and challenges of microbiome-modulating therapy for the treatment of fatty liver disease.}, }
@article {pmid31284576, year = {2019}, author = {Jackson, BR and Chow, N and Forsberg, K and Litvintseva, AP and Lockhart, SR and Welsh, R and Vallabhaneni, S and Chiller, T}, title = {On the Origins of a Species: What Might Explain the Rise of Candida auris?.}, journal = {Journal of fungi (Basel, Switzerland)}, volume = {5}, number = {3}, pages = {}, doi = {10.3390/jof5030058}, pmid = {31284576}, issn = {2309-608X}, abstract = {Candida auris is an emerging multidrug-resistant yeast first described in 2009 that has since caused healthcare-associated outbreaks of severe human infections around the world. In some hospitals, it has become a leading cause of invasive candidiasis. C. auris is markedly different from most other pathogenic Candida species in its genetics, antifungal resistance, and ability to spread between patients. The reasons why this fungus began spreading widely in the last decade remain a mystery. We examine available data on C. auris and related species, including genomic epidemiology, phenotypic characteristics, and sites of detection, to put forth hypotheses on its possible origins. C. auris has not been detected in the natural environment; related species have been detected in in plants, insects, and aquatic environments, as well as from human body sites. It can tolerate hypersaline environments and higher temperatures than most Candida species. We explore hypotheses about the pre-emergence niche of C. auris, whether in the environmental or human microbiome, and speculate on factors that might have led to its spread, including the possible roles of healthcare, antifungal use, and environmental changes, including human activities that might have expanded its presence in the environment or caused increased human contact.}, }
@article {pmid31282802, year = {2018}, author = {Amsterdam, D and Ostrov, BE}, title = {The Impact of the Microbiome on Immunosenescence.}, journal = {Immunological investigations}, volume = {47}, number = {8}, pages = {801-811}, doi = {10.1080/08820139.2018.1537570}, pmid = {31282802}, issn = {1532-4311}, abstract = {Human microbiome investigations now provide evidence that changes in the microbiome over time and their interaction with the immune, endocrine, and nervous systems are associated with a wide array of disorders. Human immunological studies typically absent a microbiome consideration in their investigations. An area of recent exploration is the role of the microbiome as a critical partner in the development and function of the human immune system in aging. It is well known that immunologic maturation is influenced by a lifetime of interactions of the host with its companion microbiome. It is generally not well recognized that intestinal microbes play an essential role in the development and expansion of gut mucosal and systemic immune function. Gut microbial communities of elderly people have different composition and behavior compared to healthy younger adults. Comorbidities associated with microbial pathogens and an aberrant immune system tend to increase with aging. This review underscores the impact of the human-microbiome interface on the development and function of the immune system and on immunosenescence. These changes have important implications regarding health and health system utilization in the elderly population.}, }
@article {pmid31279340, year = {2019}, author = {Velsko, IM and Fellows Yates, JA and Aron, F and Hagan, RW and Frantz, LAF and Loe, L and Martinez, JBR and Chaves, E and Gosden, C and Larson, G and Warinner, C}, title = {Microbial differences between dental plaque and historic dental calculus are related to oral biofilm maturation stage.}, journal = {Microbiome}, volume = {7}, number = {1}, pages = {102}, doi = {10.1186/s40168-019-0717-3}, pmid = {31279340}, issn = {2049-2618}, support = {143/108//John Fell Fund, University of Oxford/ ; BCS-1516633//National Science Foundation (US)/ ; }, abstract = {BACKGROUND: Dental calculus, calcified oral plaque biofilm, contains microbial and host biomolecules that can be used to study historic microbiome communities and host responses. Dental calculus does not typically accumulate as much today as historically, and clinical oral microbiome research studies focus primarily on living dental plaque biofilm. However, plaque and calculus reflect different conditions of the oral biofilm, and the differences in microbial characteristics between the sample types have not yet been systematically explored. Here, we compare the microbial profiles of modern dental plaque, modern dental calculus, and historic dental calculus to establish expected differences between these substrates.<br><br>RESULTS: Metagenomic data was generated from modern and historic calculus samples, and dental plaque metagenomic data was downloaded from the Human Microbiome Project. Microbial composition and functional profile were assessed. Metaproteomic data was obtained from a subset of historic calculus samples. Comparisons between microbial, protein, and metabolomic profiles revealed distinct taxonomic and metabolic functional profiles between plaque, modern calculus, and historic calculus, but not between calculus collected from healthy teeth and periodontal disease-affected teeth. Species co-exclusion was related to biofilm environment. Proteomic profiling revealed that healthy tooth samples contain low levels of bacterial virulence proteins and a robust innate immune response. Correlations between proteomic and metabolomic profiles suggest co-preservation of bacterial lipid membranes and membrane-associated proteins.<br><br>CONCLUSIONS: Overall, we find that there are systematic microbial differences between plaque and calculus related to biofilm physiology, and recognizing these differences is important for accurate data interpretation in studies comparing dental plaque and calculus.}, }
@article {pmid31278975, year = {2019}, author = {Soligo, M and Albini, M and Bertoli, FL and Marzano, V and Protto, V and Bracci-Laudiero, L and Minnone, G and De Benedetti, F and Chiaretti, A and Mantuano, E and Manni, L}, title = {Different responses of PC12 cells to different pro-nerve growth factor protein variants.}, journal = {Neurochemistry international}, volume = {129}, number = {}, pages = {104498}, doi = {10.1016/j.neuint.2019.104498}, pmid = {31278975}, issn = {1872-9754}, abstract = {The present work aimed to explore the innovative hypothesis that different transcript/protein variants of a pro-neurotrophin may generate different biological outcomes in a cellular system. Nerve growth factor (NGF) is important in the development and progression of neurodegenerative and cancer conditions. Mature NGF (mNGF) originates from a precursor, proNGF, produced in mouse in two major variants, proNGF-A and proNGF-B. Different receptors bind mNGF and proNGF, generating neurotrophic or neurotoxic outcomes. It is known that dysregulation in the proNGF/mNGF ratio and in NGF-receptors expression affects brain homeostasis. To date, however, the specific roles of the two major proNGF variants remain unexplored. Here we attempted a first characterization of the possible differential effects of proNGF-A and proNGF-B on viability, differentiation and endogenous ngf gene expression in the PC12 cell line. We also investigated the differential involvement of NGF receptors in the actions of proNGF. We found that native mouse mNGF, proNGF-A and proNGF-B elicited different effects on PC12 cell survival and differentiation. Only mNGF and proNGF-A promoted neurotrophic responses when all NGF receptors are exposed at the cell surface. Tropomyosine receptor kinase A (TrkA) blockade inhibited cell differentiation, regardless of which NGF was added to culture media. Only proNGF-A exerted a pro-survival effect when TrkA was inhibited. Conversely, proNGF-B exerted differentiative effects when the p75 neurotrophin receptor (p75NTR) was antagonized. Stimulation with NGF variants differentially regulated the autocrine production of distinct proNgf mRNA. Overall, our findings suggest that mNGF and proNGF-A may elicit similar neurotrophic effects, not necessarily linked to activation of the same NGF-receptor, while the action of proNGF-B may be determined by the NGF-receptors balance. Thus, the proposed involvement of proNGF/NGF on the development and progression of neurodegenerative and tumor conditions may depend on the NGF-receptors balance, on specific NGF trancript expression and on the proNGF protein variant ratio.}, }
@article {pmid31277695, year = {2019}, author = {Ilves, M and Kinaret, PAS and Ndika, J and Karisola, P and Marwah, V and Fortino, V and Fedutik, Y and Correia, M and Ehrlich, N and Loeschner, K and Besinis, A and Vassallo, J and Handy, RD and Wolff, H and Savolainen, K and Greco, D and Alenius, H}, title = {Surface PEGylation suppresses pulmonary effects of CuO in allergen-induced lung inflammation.}, journal = {Particle and fibre toxicology}, volume = {16}, number = {1}, pages = {28}, doi = {10.1186/s12989-019-0309-1}, pmid = {31277695}, issn = {1743-8977}, support = {309329//European Community's Seventh Framework Programme (FP7/2007-2013)/ ; }, abstract = {BACKGROUND: Copper oxide (CuO) nanomaterials are used in a wide range of industrial and commercial applications. These materials can be hazardous, especially if they are inhaled. As a result, the pulmonary effects of CuO nanomaterials have been studied in healthy subjects but limited knowledge exists today about their effects on lungs with allergic airway inflammation (AAI). The objective of this study was to investigate how pristine CuO modulates allergic lung inflammation and whether surface modifications can influence its reactivity. CuO and its carboxylated (CuO COOH), methylaminated (CuO NH3) and PEGylated (CuO PEG) derivatives were administered here on four consecutive days via oropharyngeal aspiration in a mouse model of AAI. Standard genome-wide gene expression profiling as well as conventional histopathological and immunological methods were used to investigate the modulatory effects of the nanomaterials on both healthy and compromised immune system.<br><br>RESULTS: Our data demonstrates that although CuO materials did not considerably influence hallmarks of allergic airway inflammation, the materials exacerbated the existing lung inflammation by eliciting dramatic pulmonary neutrophilia. Transcriptomic analysis showed that CuO, CuO COOH and CuO NH3 commonly enriched neutrophil-related biological processes, especially in healthy mice. In sharp contrast, CuO PEG had a significantly lower potential in triggering changes in lungs of healthy and allergic mice revealing that surface PEGylation suppresses the effects triggered by the pristine material.<br><br>CONCLUSIONS: CuO as well as its functionalized forms worsen allergic airway inflammation by causing neutrophilia in the lungs, however, our results also show that surface PEGylation can be a promising approach for inhibiting the effects of pristine CuO. Our study provides information for health and safety assessment of modified CuO materials, and it can be useful in the development of nanomedical applications.}, }
@article {pmid31275260, year = {2019}, author = {Rodionov, DA and Arzamasov, AA and Khoroshkin, MS and Iablokov, SN and Leyn, SA and Peterson, SN and Novichkov, PS and Osterman, AL}, title = {Micronutrient Requirements and Sharing Capabilities of the Human Gut Microbiome.}, journal = {Frontiers in microbiology}, volume = {10}, number = {}, pages = {1316}, doi = {10.3389/fmicb.2019.01316}, pmid = {31275260}, issn = {1664-302X}, support = {R01 DK030292/DK/NIDDK NIH HHS/United States ; R01 GM108527/GM/NIGMS NIH HHS/United States ; }, abstract = {The human gut microbiome harbors a diverse array of metabolic pathways contributing to its development and homeostasis via a complex web of diet-dependent metabolic interactions within the microbial community and host. Genomics-based reconstruction and predictive modeling of these interactions would provide a framework for diagnostics and treatment of dysbiosis-related syndromes via rational selection of therapeutic prebiotics and dietary nutrients. Of particular interest are micronutrients, such as B-group vitamins, precursors of indispensable metabolic cofactors, that are produced de novo by some gut bacteria (prototrophs) but must be provided exogenously in the diet for many other bacterial species (auxotrophs) as well as for the mammalian host. Cross-feeding of B vitamins between prototrophic and auxotrophic species is expected to strongly contribute to the homeostasis of microbial communities in the distal gut given the efficient absorption of dietary vitamins in the upper gastrointestinal tract. To confidently estimate the balance of microbiome micronutrient biosynthetic capabilities and requirements using available genomic data, we have performed a subsystems-based reconstruction of biogenesis, salvage and uptake for eight B vitamins (B1, B2, B3, B5, B6, B7, B9, and B12) and queuosine (essential factor in tRNA modification) over a reference set of 2,228 bacterial genomes representing 690 cultured species of the human gastrointestinal microbiota. This allowed us to classify the studied organisms with respect to their pathway variants and infer their prototrophic vs. auxotrophic phenotypes. In addition to canonical vitamin pathways, several conserved partial pathways were identified pointing to alternative routes of syntrophic metabolism and expanding a microbial vitamin &quot;menu&quot; by several pathway intermediates (vitamers) such as thiazole, quinolinate, dethiobiotin, pantoate. A cross-species comparison was applied to assess the extent of conservation of vitamin phenotypes at distinct taxonomic levels (from strains to families). The obtained reference collection combined with 16S rRNA gene-based phylogenetic profiles was used to deduce phenotype profiles of the human gut microbiota across in two large cohorts. This analysis provided the first estimate of B-vitamin requirements, production and sharing capabilities in the human gut microbiome establishing predictive phenotype profiling as a new approach to classification of microbiome samples. Future expansion of our reference genomic collection of metabolic phenotypes will allow further improvement in coverage and accuracy of predictive phenotype profiling of the human microbiome.}, }
@article {pmid31264406, year = {2019}, author = {Claassens, NJ and Finger-Bou, M and Scholten, B and Muis, F and de Groot, JJ and de Gier, JW and de Vos, WM and van der Oost, J}, title = {Bicistronic Design-Based Continuous and High-Level Membrane Protein Production in Escherichia coli.}, journal = {ACS synthetic biology}, volume = {8}, number = {7}, pages = {1685-1690}, doi = {10.1021/acssynbio.9b00101}, pmid = {31264406}, issn = {2161-5063}, abstract = {Escherichia coli has been widely used as a platform microorganism for both membrane protein production and cell factory engineering. The current methods to produce membrane proteins in this organism require the induction of target gene expression and often result in unstable, low yields. Here, we present a method combining a constitutive promoter with a library of bicistronic design (BCD) elements, which enables inducer-free, tuned translation initiation for optimal protein production. Our system mediates stable, constitutive production of bacterial membrane proteins at yields that outperform those obtained with E. coli Lemo21(DE3), the current gold standard for bacterial membrane protein production. We envisage that the continuous, fine-tunable, and high-level production of membrane proteins by our method will greatly facilitate their study and their utilization in engineering cell factories.}, }
@article {pmid31263750, year = {2019}, author = {Katsnelson, A}, title = {Standards Seekers Put the Human Microbiome in Their Sights.}, journal = {ACS central science}, volume = {5}, number = {6}, pages = {929-932}, doi = {10.1021/acscentsci.9b00557}, pmid = {31263750}, issn = {2374-7943}, }
@article {pmid31263284, year = {2019}, author = {Depommier, C and Everard, A and Druart, C and Plovier, H and Van Hul, M and Vieira-Silva, S and Falony, G and Raes, J and Maiter, D and Delzenne, NM and de Barsy, M and Loumaye, A and Hermans, MP and Thissen, JP and de Vos, WM and Cani, PD}, title = {Supplementation with Akkermansia muciniphila in overweight and obese human volunteers: a proof-of-concept exploratory study.}, journal = {Nature medicine}, volume = {25}, number = {7}, pages = {1096-1103}, doi = {10.1038/s41591-019-0495-2}, pmid = {31263284}, issn = {1546-170X}, support = {336452//European Research Council/International ; }, abstract = {Metabolic syndrome is characterized by a constellation of comorbidities that predispose individuals to an increased risk of developing cardiovascular pathologies as well as type 2 diabetes mellitus1. The gut microbiota is a new key contributor involved in the onset of obesity-related disorders2. In humans, studies have provided evidence for a negative correlation between Akkermansia muciniphila abundance and overweight, obesity, untreated type 2 diabetes mellitus or hypertension3-8. Since the administration of A. muciniphila has never been investigated in humans, we conducted a randomized, double-blind, placebo-controlled pilot study in overweight/obese insulin-resistant volunteers; 40 were enrolled and 32 completed the trial. The primary end points were safety, tolerability and metabolic parameters (that is, insulin resistance, circulating lipids, visceral adiposity and body mass). Secondary outcomes were gut barrier function (that is, plasma lipopolysaccharides) and gut microbiota composition. In this single-center study, we demonstrated that daily oral supplementation of 1010 A. muciniphila bacteria either live or pasteurized for three months was safe and well tolerated. Compared to placebo, pasteurized A. muciniphila improved insulin sensitivity (+28.62 ± 7.02%, P = 0.002), and reduced insulinemia (-34.08 ± 7.12%, P = 0.006) and plasma total cholesterol (-8.68 ± 2.38%, P = 0.02). Pasteurized A. muciniphila supplementation slightly decreased body weight (-2.27 ± 0.92 kg, P = 0.091) compared to the placebo group, and fat mass (-1.37 ± 0.82 kg, P = 0.092) and hip circumference (-2.63 ± 1.14 cm, P = 0.091) compared to baseline. After three months of supplementation, A. muciniphila reduced the levels of the relevant blood markers for liver dysfunction and inflammation while the overall gut microbiome structure was unaffected. In conclusion, this proof-of-concept study (clinical trial no. NCT02637115) shows that the intervention was safe and well tolerated and that supplementation with A. muciniphila improves several metabolic parameters.}, }
@article {pmid31262073, year = {2019}, author = {Tavakoli, A and Flanagan, JL}, title = {The Case for a More Holistic Approach to Dry Eye Disease: Is It Time to Move beyond Antibiotics?.}, journal = {Antibiotics (Basel, Switzerland)}, volume = {8}, number = {3}, pages = {}, doi = {10.3390/antibiotics8030088}, pmid = {31262073}, issn = {2079-6382}, abstract = {Dry eye disease (DED) is one of the most frequent presentations to optometrists with over 16 million US adults (6.8% of adult population) diagnosed as having this disorder. The majority of associated marketed products offer relief from symptomatology but do not address aetiology. DED harbours many distinguishing features of a chronic inflammatory disorder. The recent explosion in human microbiome research has sparked interest in the ocular microbiome and its role in the preservation and extension of ocular surface health and in the contribution of the gut microbiome to chronic systemic inflammation and associated &quot;Western life-style&quot; diseases. With a significant lack of success for many patients using currently available DED treatments, in this era of the microbiome, we are interested in exploring potential novel therapies that aim to reconstitute healthy bacterial communities both locally and distally (in the gut) as a treatment for DED. Although this direction of investigation is in its infancy, burgeoning interest makes such a review timely. This paper considers a number of studies into the use functional foods and associated products to ameliorate dry eye.}, }
@article {pmid31261078, year = {2019}, author = {Valentine, G and Prince, A and Aagaard, KM}, title = {The Neonatal Microbiome and Metagenomics: What Do We Know and What Is the Future?.}, journal = {NeoReviews}, volume = {20}, number = {5}, pages = {e258-e271}, doi = {10.1542/neo.20-5-e258}, pmid = {31261078}, issn = {1526-9906}, abstract = {The human microbiota includes the trillions of microorganisms living in the human body whereas the human microbiome includes the genes and gene products of this microbiota. Bacteria were historically largely considered to be pathogens that inevitably led to human disease. However, because of advances in both cultivation-based methods and the advent of metagenomics, bacteria are now recognized to be largely beneficial commensal organisms and thus, key to normal and healthy human development. This relatively new area of medical research has elucidated insights into diseases such as inflammatory bowel disease and obesity, as well as metabolic and atopic disorders. However, much remains unknown about the complexity of microbe-microbe and microbe-host interactions. Future efforts aimed at answering key questions pertaining to the early establishment of the microbiome, alongside what defines its dysbiosis, will likely lead to long-term health and mitigation of disease. Here, we review the relevant literature pertaining to modulations in the perinatal and neonatal microbiome, the impact of environmental and maternal factors in shaping the neonatal microbiome, and future questions and directions in the exciting emerging arena of metagenomic medicine.}, }
@article {pmid31253623, year = {2019}, author = {Korpela, K and Dikareva, E and Hanski, E and Kolho, KL and de Vos, WM and Salonen, A}, title = {Cohort profile: Finnish Health and Early Life Microbiota (HELMi) longitudinal birth cohort.}, journal = {BMJ open}, volume = {9}, number = {6}, pages = {e028500}, doi = {10.1136/bmjopen-2018-028500}, pmid = {31253623}, issn = {2044-6055}, abstract = {PURPOSE: HELMi (Health and Early Life Microbiota) is a longitudinal, prospective general population birth cohort, set up to identify environmental, lifestyle and genetic factors that modify the intestinal microbiota development in the first years of life and their relation to child health and well-being.<br><br>PARTICIPANTS: The HELMi cohort consists of 1055 healthy term infants born in 2016-2018 mainly at the capital region of Finland and their parents. The intestinal microbiota development of the infants is characterised based on nine, strategically selected, faecal samples and connected to extensive online questionnaire-collected metadata at weekly to monthly intervals focusing on the diet, other exposures and family's lifestyle as well as the health and growth of the child. Motor and cognitive developmental screening takes place at 18 months. Infant's DNA sample, mother's breast milk sample and both parent's spot faecal samples have been collected.<br><br>FINDINGS TO DATE: The mean age of the mothers was 32.8 (SD 4.1) and fathers/coparents 34.8 (5.3) years at the time of enrolment. Seventeen percentage (n=180) of the infants were born by caesarean section. Just under half (49%) were firstborns; 50.7% were males. At 3 months of age, 86% of the babies were exclusively breastfed and 2% exclusively formula-fed.<br><br>FUTURE PLANS: The current follow-up from pregnancy to first 24 months will be completed in March 2020, totalling to over 10 000 biological samples and over 50 000 questionnaire entries. The results are expected to identify environmental and host factors that affect early gut microbiota development and health, and hence give indications of how to prevent or reverse microbiota perturbations in infancy. This prospective cohort will be followed up further to identify how the early microbiota relates to later health outcomes, especially weight gain, infections and allergic and other chronic diseases.<br><br>TRIAL REGISTRATION NUMBER: NCT03996304; Pre-results.}, }
@article {pmid31253198, year = {2019}, author = {Lokugamage, AU and Pathberiya, SDC}, title = {The microbiome seeding debate - let's frame it around women-centred care.}, journal = {Reproductive health}, volume = {16}, number = {1}, pages = {91}, doi = {10.1186/s12978-019-0747-0}, pmid = {31253198}, issn = {1742-4755}, abstract = {In a global culture that is increasingly interested in ecological interventions, probiotics, 'friendly bacteria', microbiome preservation/restoration and long-term health, there is growing awareness of the idea of seeding the vaginal microbiome in the new born after caesarean section. It is postulated as a way of restoring helpful missing microbes and preventing long term non-communicable diseases of babies delivered by caesarean section. Currently, there is a deluge of evidence being published on the human microbiome, which can be challenging to digest and absorb by scientists, clinicians and patients. The specific evidence base around this technique is at its early stages. This commentary discusses what advice is currently available from a feminist and a person-centred care perspective.<br><br>ABSTRAKT: Det er en voksende interesse internasjonalt for økologiske intervensjoner, probiotika, 'snille bakterier', bevaring/gjenoppretting av. mikrobiomet og helse i et langtidsperspektiv. I denne sammenhengen er det en økende interesse for tanken om å så det vaginale mikrobiomet (vaginal seeding) på den nyfødte etter et keisersnitt. Dette er postulert som en måte å gjenopprette manglende normalflora/mikrobiom og forebygge langvarige ikke-smittsomme sykdommer hos barn født med keisersnitt. For tiden publiseres det mye forskning om menneskets mikrobiom, noe som kan være utfordrende å fordøye og ta til seg for forskere, klinikere og pasienter. Forskningen på denne spesifikke metoden er i sin begynnelse. Denne kommentaren drøfter hvilke råd som for øyeblikket er tilgjengelige, fra et feministisk og personsentrert omsorgsperspektiv. POPULARISERT SAMMENDRAG På NORSK: Det menneskelige mikrobiomet er summen av alle bakteriene som dekker den menneskelige kroppen og det hjelper kroppen i å fungere optimalt. Når mikrobiomet forstyrres, vil kroppen kunne få betennelsesreaksjoner og allergier. I fødsel finnes de «gode» bakteriene i kvinnens vagina. (det vaginale mikrobiomet) som man tror vil være fordelaktig for babyens evne til å utvikle et sunt immunsystem. Babyer som er født med keisersnitt vil ikke bli eksponert for disse «gode» bakteriene og det kan påvirke barnets immunforsvar negativt og potensielt øke sjansen for allergier og betennelsesreaksjoner i kroppen på lang sikt. Vaginal seeding (et forsøk på å gjenopprette balansen og noen av de gode bakterier i spedbarnet gjennom å tilføre mors vaginale bakterier via en kompress som strykes over spedbarnets ansikt) Vaginal seeding er en metode som noen forskere sier muligens delvis gjenoppretter de manglende «gode» bakteriene etter et keisersnitt. Forskningen er på et tidlig stadium. Det har vært avisartikler og en film om emnet og mødre har funnet ut om vaginal seeding som en måte å gjenopprette denne delen av babyens mikrobiom. Foreldre ønsker å diskutere vaginal seeding, men på nåværende tidspunkt er helsevesenet avventende og helsepersonell er ikke godt nok informert. Denne artikkelen vil se på den pågående diskusjonen. RéSUMé: Dans une culture mondiale qui s'intéresse de plus en plus aux interventions écologiques, aux probiotiques, aux «bactéries amicales», à la préservation / restauration du microbiome et à la santé à long terme, on commence à prendre conscience de l'idée d'ensemencer le microbiome vaginal chez le nouveau-né après une césarienne. Il est postulé comme un moyen de restaurer les microbes manquants et d'aider à prévenir les maladies non transmissibles à long terme des bébés mis au monde par césarienne. Il existe actuellement un déluge de preuves sur le microbiome humain, qui peuvent être difficiles à digérer et à absorber par les scientifiques, les cliniciens et les patients. La base de preuves spécifique autour de cette technique en est à ses débuts. Ce commentaire discute des conseils actuellement disponibles dans une perspective de soins féministe et centrée sur la personne. RéSUMé SIMPLIFIé: Le microbiome humain est constitué de tous les microbes qui recouvrent le corps humain et qui aident le corps à bien fonctionner. Lorsque le microbiome est perturbé, le corps devient plus inflammatoire et est sujet aux allergies. Lors de l'accouchement, le vagin d'une mère (le microbiome vaginal) contient des &quot;bactéries amicales&quot; qui pourraient être bénéfiques pour l'enfant et aider le bébé à développer un système immunitaire en bonne santé. Les bébés nés par césarienne ne sont généralement pas exposés à ces «bactéries bénéfiques», ce qui pourrait affecter négativement le système immunitaire du bébé et potentiellement augmenter le risque d'allergies et d'inflammation à long terme. Selon certains scientifiques, l'ensemencement vaginal pourrait partiellement restaurer les «bactéries amies» manquantes après la césarienne. La recherche en est à ses débuts. Il y a eu des articles de journaux et un film à ce sujet, et les mères ont découvert l'existence d'un ensemencement vaginal (où une compresse placée dans le vagin de la mère pourrait être appliquée sur l'enfant après la césarienne) afin de restaurer une partie du microbiome du bébé. Les parents souhaitent discuter de l'ensemencement vaginal, mais à l'heure actuelle, les organisations médicales sont prudentes et les praticiens ne sont pas suffisamment informés. Cet article examine le débat en cours.<br><br>RESUMO: Numa cultura global que está cada vez mais interessada em intervenções ecológicas, probióticos, &quot;bactérias amigáveis&quot;, preservação/restauração do microbioma e saúde a longo prazo, há uma crescente consciência sobre a ideia de semear o microbioma vaginal no recém-nascido após uma cirurgia cesariana. Isso está sendo postulado como uma forma de restaurar micróbios úteis que lhe faltariam e prevenir doenças não transmissíveis em longo prazo para bebês que nasceram pela via cirúrgica. Atualmente, há um aumento massivo de evidências sendo publicadas sobre o microbioma humano cuja absorção e digestão pode ser desafiadora para cientistas, clínicos e pacientes. A base específica da evidência que cerca essa técnica ainda está em estágios preliminares. Este comentário discute o aconselhamento atualmente disponível numa perspectiva feminista e centrada na pessoa. SíNTESE SIMPLIFICADA: O microbioma humano está composto por todos os micróbios que cobrem o corpo humano e que ajudam o corpo a funcionar bem. Quando o microbioma é perturbado, o corpo tem mais inflamações e maior propensão a desenvolver alergias. Ao nascimento, há &quot;bactérias amigáveis&quot; na vagina materna (o microbioma vaginal) que podem ser benéficas à criança e ajudar o bebê a desenvolver um sistema imunológico saudável. Bebês que nascem por cesariana usualmente não são expostos a essas &quot;bactérias amigáveis&quot; e isso poderá afetar negativamente o sistema imunológico do bebê, aumentando potencialmente a probabilidade de alegrias e inflamações no longo prazo. A semeadura de bactéria vaginais é um método que alguns cientistas afirmam que poderá restaurar parcialmente as &quot;bactérias amigáveis&quot; faltantes depois de uma cesariana. Essa pesquisa está em fase preliminar. Houve alguns artigos em jornais e um filme sobre isso, e as mães descobriram a possibilidade da semeadura vaginal (quando é feito um swab da vagina materna que é esfregado no bebê após a cesárea) para restaurar parte do microbioma do bebê. Pais desejam discutir a semeadura vaginal, mas, no momento, as organizações médicas têm sido cautelosas e os profissionais não estão adequadamente informados. Este artigo aborda o debate em andamento.<br><br>RESUMEN: En una cultura global que está cada vez más interesada en las intervenciones ecológicas, los probióticos, las &quot;bacterias amigables&quot;, la conservación/restauración de microbiomas y la salud a largo plazo, hay una creciente conciencia de la idea de sembrar el microbioma vaginal en el recién nacido después de la cesárea. Se postula como una forma de restaurar los microbios útiles faltantes y prevenir las enfermedades no transmisibles a largo plazo de los bebés nacidos por cesárea. Actualmente, se está publicando una gran cantidad de pruebas sobre el microbioma humano, que pueden ser difíciles de digerir y absorber por parte de científicos, clínicos y pacientes. La base de la evidencia específica en torno a esta técnica se encuentra en sus primeras etapas. Este artículo analiza qué consejos están disponibles actualmente desde una perspectiva feminista y de atención centrada en la persona.<br><br>RESUMEN EN LENGUAJE SENCILLO: El microbioma humano está hecho de todos las bacterias que cubren el cuerpo humano y que ayudan al cuerpo a funcionar bien. Cuando se altera el microbioma, el cuerpo se inflama más y es propenso a las alergias. En el parto, hay &quot;bacterias amigables&quot; en la vagina de la madre (el microbioma vaginal) que podrían ser beneficiosas para el niño y ayudar al bebé a desarrollar un sistema inmunológico saludable. Los bebés que nacen por cesárea generalmente no se exponen a estas &quot;bacterias amigables&quot; y esto podría afectar negativamente el sistema inmunológico del bebé, lo que podría aumentar la probabilidad de alergias e inflamación a largo plazo. La siembra vaginal es un método que algunos científicos dicen que podría restaurar parcialmente las &quot;bacterias amigables&quot; que faltan después de la cesárea. La investigación se encuentra en sus primeras etapas. Han habido artículos periodísticos y una película sobre esto, y las madres se han enterado de la siembra vaginal (donde se puede frotar el niño con una torunda de la vagina de la madre después de la cesárea) para restaurar la parte del microbioma del bebé. Los padres quieren hablar sobre la siembra vaginal, pero en la actualidad las organizaciones médicas son cautelosas y los profesionales no están informados adecuadamente. Este artículo analiza el debate en curso.}, }
@article {pmid31246421, year = {2019}, author = {Gumkowski, JD and Martinie, RJ and Corrigan, PS and Pan, J and Bauerle, MR and Almarei, M and Booker, SJ and Silakov, A and Krebs, C and Boal, AK}, title = {Analysis of RNA Methylation by Phylogenetically Diverse Cfr Radical S-Adenosylmethionine Enzymes Reveals an Iron-Binding Accessory Domain in a Clostridial Enzyme.}, journal = {Biochemistry}, volume = {58}, number = {29}, pages = {3169-3184}, doi = {10.1021/acs.biochem.9b00197}, pmid = {31246421}, issn = {1520-4995}, abstract = {Cfr is a radical S-adenosylmethionine (SAM) RNA methylase linked to multidrug antibiotic resistance in bacterial pathogens. It catalyzes a chemically challenging C-C bond-forming reaction to methylate C8 of A2503 (Escherichia coli numbering) of 23S rRNA during ribosome assembly. The cfr gene has been identified as a mobile genetic element in diverse bacteria and in the genome of select Bacillales and Clostridiales species. Despite the importance of Cfr, few representatives have been purified and characterized in vitro. Here we show that Cfr homologues from Bacillus amyloliquefaciens, Enterococcus faecalis, Paenibacillus lautus, and Clostridioides difficile act as C8 adenine RNA methylases in biochemical assays. C. difficile Cfr contains an additional Cys-rich C-terminal domain that binds a mononuclear Fe2+ ion in a rubredoxin-type Cys4 motif. The C-terminal domain can be truncated with minimal impact on C. difficile Cfr activity, but the rate of turnover is decreased upon disruption of the Fe2+-binding site by Zn2+ substitution or ligand mutation. These findings indicate an important purpose for the observed C-terminal iron in the native fusion protein. Bioinformatic analysis of the C. difficile Cfr Cys-rich domain shows that it is widespread (∼1400 homologues) as a stand-alone gene in pathogenic or commensal Bacilli and Clostridia, with >10% encoded adjacent to a predicted radical SAM RNA methylase. Although the domain is not essential for in vitro C. difficile Cfr activity, the genomic co-occurrence and high abundance in the human microbiome suggest a possible functional role for a specialized rubredoxin in certain radical SAM RNA methylases that are relevant to human health.}, }
@article {pmid31231350, year = {2019}, author = {Savijoki, K and Nyman, TA and Kainulainen, V and Miettinen, I and Siljamäki, P and Fallarero, A and Sandholm, J and Satokari, R and Varmanen, P}, title = {Growth Mode and Carbon Source Impact the Surfaceome Dynamics of Lactobacillus rhamnosus GG.}, journal = {Frontiers in microbiology}, volume = {10}, number = {}, pages = {1272}, doi = {10.3389/fmicb.2019.01272}, pmid = {31231350}, issn = {1664-302X}, abstract = {Bacterial biofilms have clear implications in disease and in food applications involving probiotics. Here, we show that switching the carbohydrate source from glucose to fructose increased the biofilm formation and the total surface-antigenicity of a well-known probiotic, Lactobacillus rhamnosus GG. Surfaceomes (all cell surface-associated proteins) of GG cells grown with glucose and fructose in planktonic and biofilm cultures were identified and compared, which indicated carbohydrate source-dependent variations, especially during biofilm growth. The most distinctive differences under these conditions were detected with several surface adhesins (e.g., MBF, SpaC pilus protein and penicillin-binding proteins), enzymes (glycoside hydrolases, PrsA, PrtP, PrtR, and HtrA) and moonlighting proteins (glycolytic, transcription/translation and stress-associated proteins, r-proteins, tRNA synthetases, Clp family proteins, PepC, PepN, and PepA). The abundance of several known adhesins and candidate moonlighters, including enzymes acting on casein-derived peptides (ClpP, PepC, and PepN), increased in the biofilm cells grown on fructose, from which the surface-associated aminopeptidase activity mediated by PepC and PepN was further confirmed by an enzymatic assay. The mucus binding factor (MBF) was found most abundant in fructose grown biofilm cells whereas SpaC adhesin was identified specifically from planktonic cells growing on fructose. An additional indirect ELISA indicated both growth mode- and carbohydrate-dependent differences in abundance of SpaC, whereas the overall adherence of GG assessed with porcine mucus indicated that the carbon source and the growth mode affected mucus adhesion. The adherence of GG cells to mucus was almost completely inhibited by anti-SpaC antibodies regardless of growth mode and/or carbohydrate source, indicating the key role of the SpaCBA pilus in adherence under the tested conditions. Altogether, our results suggest that carbon source and growth mode coordinate mechanisms shaping the proteinaceous composition of GG cell surface, which potentially contributes to resistance, nutrient acquisition and cell-cell interactions under different conditions. In conclusion, the present study shows that different growth regimes and conditions can have a profound impact on the adherent and antigenic features of GG, thereby providing new information on how to gain additional benefits from this probiotic.}, }
@article {pmid31231319, year = {2019}, author = {Stinson, LF and Boyce, MC and Payne, MS and Keelan, JA}, title = {The Not-so-Sterile Womb: Evidence That the Human Fetus Is Exposed to Bacteria Prior to Birth.}, journal = {Frontiers in microbiology}, volume = {10}, number = {}, pages = {1124}, doi = {10.3389/fmicb.2019.01124}, pmid = {31231319}, issn = {1664-302X}, abstract = {The human microbiome includes trillions of bacteria, many of which play a vital role in host physiology. Numerous studies have now detected bacterial DNA in first-pass meconium and amniotic fluid samples, suggesting that the human microbiome may commence in utero. However, these data have remained contentious due to underlying contamination issues. Here, we have used a previously described method for reducing contamination in microbiome workflows to determine if there is a fetal bacterial microbiome beyond the level of background contamination. We recruited 50 women undergoing non-emergency cesarean section deliveries with no evidence of intra-uterine infection and collected first-pass meconium and amniotic fluid samples. Full-length 16S rRNA gene sequencing was performed using PacBio SMRT cell technology, to allow high resolution profiling of the fetal gut and amniotic fluid bacterial microbiomes. Levels of inflammatory cytokines were measured in amniotic fluid, and levels of immunomodulatory short chain fatty acids (SCFAs) were quantified in meconium. All meconium samples and most amniotic fluid samples (36/43) contained bacterial DNA. The meconium microbiome was dominated by reads that mapped to Pelomonas puraquae. Aside from this species, the meconium microbiome was remarkably heterogeneous between patients. The amniotic fluid microbiome was more diverse and contained mainly reads that mapped to typical skin commensals, including Propionibacterium acnes and Staphylococcus spp. All meconium samples contained acetate and propionate, at ratios similar to those previously reported in infants. P. puraquae reads were inversely correlated with meconium propionate levels. Amniotic fluid cytokine levels were associated with the amniotic fluid microbiome. Our results demonstrate that bacterial DNA and SCFAs are present in utero, and have the potential to influence the developing fetal immune system.}, }
@article {pmid31220972, year = {2019}, author = {Koontz, JM and Dancy, BCR and Horton, CL and Stallings, JD and DiVito, VT and Lewis, JA}, title = {The Role of the Human Microbiome in Chemical Toxicity.}, journal = {International journal of toxicology}, volume = {38}, number = {4}, pages = {251-264}, doi = {10.1177/1091581819849833}, pmid = {31220972}, issn = {1092-874X}, abstract = {There is overwhelming evidence that the microbiome must be considered when evaluating the toxicity of chemicals. Disruption of the normal microbial flora is a known effect of toxic exposure, and these disruptions may lead to human health effects. In addition, the biotransformation of numerous compounds has been shown to be dependent on microbial enzymes, with the potential for different host health outcomes resulting from variations in the microbiome. Evidence suggests that such metabolism of environmental chemicals by enzymes from the host's microbiota can affect the toxicity of that chemical to the host. Chemical-microbial interactions can be categorized into two classes: Microbiome Modulation of Toxicity (MMT) and Toxicant Modulation of the Microbiome (TMM). MMT refers to transformation of a chemical by microbial enzymes or metabolites to modify the chemical in a way that makes it more or less toxic. TMM is a change in the microbiota that results from a chemical exposure. These changes span a large magnitude of effects and may vary from microbial gene regulation, to inhibition of a specific enzyme, to the death of the microbes. Certain microbiomes or microbiota may become associated with different health outcomes, such as resistance or susceptibility to exposure to certain toxic chemicals, the ability to recover following a chemical-induced injury, the presence of disease-associated phenotypes, and the effectiveness of immune responses. Future work in toxicology will require an understanding of how the microbiome interacts with toxicants to fully elucidate how a compound will affect a diverse, real-world population.}, }
@article {pmid31220751, year = {2019}, author = {Zhang, YJ and Hu, HW and Chen, QL and Singh, BK and Yan, H and Chen, D and He, JZ}, title = {Transfer of antibiotic resistance from manure-amended soils to vegetable microbiomes.}, journal = {Environment international}, volume = {130}, number = {}, pages = {104912}, doi = {10.1016/j.envint.2019.104912}, pmid = {31220751}, issn = {1873-6750}, abstract = {The increasing antimicrobial resistance in manure-amended soil can potentially enter food chain, representing an important vehicle for antibiotic resistance genes (ARGs) transmission into human microbiome. However, the pathways for transmission of ARGs from soil to plant remain unclear. Here, we explored the impacts of poultry and cattle manure application on the patterns of resistome in soil and lettuce microbiome including rhizosphere, root endosphere, leaf endosphere and phyllosphere, to identify the potential transmission routes of ARGs in the soil-plant system. After 90 days of cultivation, a total of 144 ARGs were detected in all samples using high-throughput quantitative PCR. Rhizosphere soil samples harbored the most diverse ARGs compared with other components of lettuce. Cattle manure application increased the abundance of ARGs in root endophyte, while poultry manure application increased ARGs in rhizosphere, root endophyte and phyllosphere, suggesting that poultry manure may have a stronger impact on lettuce resistomes. The ARG profiles were significantly correlated with the bacterial community, and the enrichment of soil and plant resistomes was strongly affected by the bacterial taxa including Solibacteres, Chloroflexi, Acidobacteria, Gemm-1 and Gemmatimonadetes, as revealed by the network analyses. Moreover, the overlaps of ARGs between lettuce tissues and soil were identified, which indicated that plant and environmental resistomes are interconnected. Our findings provide insights into the transmission routes of ARGs from manured soil to vegetables, and highlight the potential risks of plant resistome migration to the human food chain.}, }
@article {pmid31218869, year = {2019}, author = {Shen, X and Yao, YF and Li, JY and Li, Y}, title = {[Human mycobiome and diseases].}, journal = {Hua xi kou qiang yi xue za zhi = Huaxi kouqiang yixue zazhi = West China journal of stomatology}, volume = {37}, number = {3}, pages = {314-319}, doi = {10.7518/hxkq.2019.03.017}, pmid = {31218869}, issn = {2618-0456}, mesh = {Bacteria ; *Disease ; Female ; Fungi ; Humans ; *Microbiota ; Mouth ; *Mycobiome ; }, abstract = {The proportion of mycobiome is less than 1% of human microbiome. However, fungal community plays a key role in human health and diseases. With high-throughput sequencing applications, the structure and composition of mycobiome in the mouth, lung, gut, vagina, and skin have been analyzed, and the role of microbiome in diseases has been investigated. Mycobiome also influences the composition of bacteriome and includes key species that maintain the structure and function of microbial communities. Fungi also influence host immune responses. In this review, we summarized the mycobiome com-position at various sites and different diseases and the interactions between fungi-bacteria and fungi-host.}, }
@article {pmid31202124, year = {2019}, author = {Picardo, SL and Coburn, B and Hansen, AR}, title = {The microbiome and cancer for clinicians.}, journal = {Critical reviews in oncology/hematology}, volume = {141}, number = {}, pages = {1-12}, doi = {10.1016/j.critrevonc.2019.06.004}, pmid = {31202124}, issn = {1879-0461}, abstract = {The human microbiome is an emerging target in cancer development and therapeutics. It may be directly oncogenic, through promotion of mucosal inflammation or systemic dysregulation, or may alter anti-cancer immunity/therapy. Microorganisms within, adjacent to and distant from tumors may affect cancer progression, and interactions and differences between these populations can influence the course of disease. Here we review the microbiome as it pertains to cancer for clinicians. The microbiota of cancers including colorectal, pancreas, breast and prostate are discussed. We examine &quot;omics&quot; technologies, microbiota associated with tumor tissue and tumor-site fluids such as feces and urine, as well as indirect effects of the gut microbiome. We describe roles of the microbiome in immunotherapy, and how it can be modulated to improve cancer therapeutics. While research is still at an early stage, there is potential to exploit the microbiome, as modulation may increase efficacy of treatments, reduce toxicities and prevent carcinogenesis.}, }
@article {pmid31201356, year = {2019}, author = {Szafrański, SP and Kilian, M and Yang, I and Bei der Wieden, G and Winkel, A and Hegermann, J and Stiesch, M}, title = {Diversity patterns of bacteriophages infecting Aggregatibacter and Haemophilus species across clades and niches.}, journal = {The ISME journal}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41396-019-0450-8}, pmid = {31201356}, issn = {1751-7370}, abstract = {Aggregatibacter and Haemophilus species are relevant human commensals and opportunistic pathogens. Consequently, their bacteriophages may have significant impact on human microbial ecology and pathologies. Our aim was to reveal the prevalence and diversity of bacteriophages infecting Aggregatibacter and Haemophilus species that colonize the human body. Genome mining with comparative genomics, screening of clinical isolates, and profiling of metagenomes allowed characterization of 346 phages grouped in 52 clusters and 18 superclusters. Less than 10% of the identified phage clusters were represented by previously characterized phages. Prophage diversity patterns varied significantly for different phage types, host clades, and environmental niches. A more diverse phage community lysogenizes Haemophilus influenzae and Haemophilus parainfluenzae strains than Aggregatibacter actinomycetemcomitans and &quot;Haemophilus ducreyi&quot;. Co-infections occurred more often in &quot;H. ducreyi&quot;. Phages from Aggregatibacter actinomycetemcomitans preferably lysogenized strains of specific serotype. Prophage patterns shared by subspecies clades of different bacterial species suggest similar ecoevolutionary drivers. Changes in frequencies of DNA uptake signal sequences and guanine-cytosine content reflect phage-host long-term coevolution. Aggregatibacter and Haemophilus phages were prevalent at multiple oral sites. Together, these findings should help exploring the ecoevolutionary forces shaping virus-host interactions in the human microbiome. Putative lytic phages, especially phiKZ-like, may provide new therapeutic options.}, }
@article {pmid31194675, year = {2019}, author = {Bernstein, DB and Dewhirst, FE and Segrè, D}, title = {Metabolic network percolation quantifies biosynthetic capabilities across the human oral microbiome.}, journal = {eLife}, volume = {8}, number = {}, pages = {}, doi = {10.7554/eLife.39733}, pmid = {31194675}, issn = {2050-084X}, support = {T32GM008764//National Institute of General Medical Sciences/ ; T32 GM008764/GM/NIGMS NIH HHS/United States ; R01 DE024468/DE/NIDCR NIH HHS/United States ; R01 GM121950/GM/NIGMS NIH HHS/United States ; DE-SC0012627//Biological and Environmental Research/ ; RGP0020/2016//Human Frontier Science Program/ ; NSFOCE-BSF 1635070//National Science Foundation/ ; HR0011-15-C-0091//Defense Advanced Research Projects Agency/ ; R37DE016937//National Institute of Dental and Craniofacial Research/ ; R37 DE016937/DE/NIDCR NIH HHS/United States ; R01GM121950//National Institute of General Medical Sciences/ ; R01DE024468//National Institute of Dental and Craniofacial Research/ ; 1457695//National Science Foundation/ ; }, abstract = {The biosynthetic capabilities of microbes underlie their growth and interactions, playing a prominent role in microbial community structure. For large, diverse microbial communities, prediction of these capabilities is limited by uncertainty about metabolic functions and environmental conditions. To address this challenge, we propose a probabilistic method, inspired by percolation theory, to computationally quantify how robustly a genome-derived metabolic network produces a given set of metabolites under an ensemble of variable environments. We used this method to compile an atlas of predicted biosynthetic capabilities for 97 metabolites across 456 human oral microbes. This atlas captures taxonomically-related trends in biomass composition, and makes it possible to estimate inter-microbial metabolic distances that correlate with microbial co-occurrences. We also found a distinct cluster of fastidious/uncultivated taxa, including several Saccharibacteria (TM7) species, characterized by their abundant metabolic deficiencies. By embracing uncertainty, our approach can be broadly applied to understanding metabolic interactions in complex microbial ecosystems.}, }
@article {pmid31188557, year = {2019}, author = {Kooter, I and Ilves, M and Gröllers-Mulderij, M and Duistermaat, E and Tromp, PC and Kuper, F and Kinaret, P and Savolainen, K and Greco, D and Karisola, P and Ndika, J and Alenius, H}, title = {Molecular Signature of Asthma-Enhanced Sensitivity to CuO Nanoparticle Aerosols from 3D Cell Model.}, journal = {ACS nano}, volume = {13}, number = {6}, pages = {6932-6946}, doi = {10.1021/acsnano.9b01823}, pmid = {31188557}, issn = {1936-086X}, abstract = {More than 5% of any population suffers from asthma, and there are indications that these individuals are more sensitive to nanoparticle aerosols than the healthy population. We used an air-liquid interface model of inhalation exposure to investigate global transcriptomic responses in reconstituted three-dimensional airway epithelia of healthy and asthmatic subjects exposed to pristine (nCuO) and carboxylated (nCuOCOOH) copper oxide nanoparticle aerosols. A dose-dependent increase in cytotoxicity (highest in asthmatic donor cells) and pro-inflammatory signaling within 24 h confirmed the reliability and sensitivity of the system to detect acute inhalation toxicity. Gene expression changes between nanoparticle-exposed versus air-exposed cells were investigated. Hierarchical clustering based on the expression profiles of all differentially expressed genes (DEGs), cell-death-associated DEGs (567 genes), or a subset of 48 highly overlapping DEGs categorized all samples according to &quot;exposure severity&quot;, wherein nanoparticle surface chemistry and asthma are incorporated into the dose-response axis. For example, asthmatics exposed to low and medium dose nCuO clustered with healthy donor cells exposed to medium and high dose nCuO, respectively. Of note, a set of genes with high relevance to mucociliary clearance were observed to distinctly differentiate asthmatic and healthy donor cells. These genes also responded differently to nCuO and nCuOCOOH nanoparticles. Additionally, because response to transition-metal nanoparticles was a highly enriched Gene Ontology term (FDR 8 × 10-13) from the subset of 48 highly overlapping DEGs, these genes may represent biomarkers to a potentially large variety of metal/metal oxide nanoparticles.}, }
@article {pmid31186074, year = {2019}, author = {Nichols, RG and Peters, JM and Patterson, AD}, title = {Interplay Between the Host, the Human Microbiome, and Drug Metabolism.}, journal = {Human genomics}, volume = {13}, number = {1}, pages = {27}, doi = {10.1186/s40246-019-0211-9}, pmid = {31186074}, issn = {1479-7364}, support = {ES022186//National Institute of Environmental Health Sciences/ ; ES028288//National Institute of Environmental Health Sciences/ ; ES026684//National Institute of Environmental Health Sciences/ ; Tobacco CURE//Pennsylvania Department of Health/ ; PEN04607//National Institute of Food and Agriculture/ ; PEN04607//National Institute of Food and Agriculture/ ; CA124533//National Cancer Institute/ ; }, abstract = {The human microbiome is composed of four major areas including intestinal, skin, vaginal, and oral microbiomes, with each area containing unique species and unique functionalities. The human microbiome may be modulated with prebiotics, probiotics, and postbiotics to potentially aid in the treatment of diseases like irritable bowel syndrome, bacterial vaginosis, atopic dermatitis, gingivitis, obesity, or cancer. There is also potential for many of the inhabitants of the human microbiome to directly modulate host gene expression and modulate host detoxifying enzyme activity like cytochrome P450s (CYPs), dehydrogenases, and carboxylesterases. Therefore, the microbiome may be important to consider during drug discovery, risk assessment, and dosing regimens for various diseases given that the human microbiome has been shown to impact host detoxification processes.}, }
@article {pmid31183114, year = {2019}, author = {Zhao, L and Xu, J and Shang, X and Li, X and Li, Q and Li, S}, title = {Synaptic memory devices from CoO/Nb:SrTiO3 junction.}, journal = {Royal Society open science}, volume = {6}, number = {4}, pages = {181098}, doi = {10.1098/rsos.181098}, pmid = {31183114}, issn = {2054-5703}, abstract = {Non-volatile memristors are promising for future hardware-based neurocomputation application because they are capable of emulating biological synaptic functions. Various material strategies have been studied to pursue better device performance, such as lower energy cost, better biological plausibility, etc. In this work, we show a novel design for non-volatile memristor based on CoO/Nb:SrTiO3 heterojunction. We found the memristor intrinsically exhibited resistivity switching behaviours, which can be ascribed to the migration of oxygen vacancies and charge trapping and detrapping at the heterojunction interface. The carrier trapping/detrapping level can be finely adjusted by regulating voltage amplitudes. Gradual conductance modulation can therefore be realized by using proper voltage pulse stimulations. And the spike-timing-dependent plasticity, an important Hebbian learning rule, has been implemented in the device. Our results indicate the possibility of achieving artificial synapses with CoO/Nb:SrTiO3 heterojunction. Compared with filamentary type of the synaptic device, our device has the potential to reduce energy consumption, realize large-scale neuromorphic system and work more reliably, since no structural distortion occurs.}, }
@article {pmid31169619, year = {2019}, author = {Wijeyesekera, A and Wagner, J and De Goffau, M and Thurston, S and Rodrigues Sabino, A and Zaher, S and White, D and Ridout, J and Peters, MJ and Ramnarayan, P and Branco, RG and Torok, ME and Valla, F and Meyer, R and Klein, N and Frost, G and Parkhill, J and Holmes, E and Pathan, N}, title = {Multi-Compartment Profiling of Bacterial and Host Metabolites Identifies Intestinal Dysbiosis and Its Functional Consequences in the Critically Ill Child.}, journal = {Critical care medicine}, volume = {47}, number = {9}, pages = {e727-e734}, doi = {10.1097/CCM.0000000000003841}, pmid = {31169619}, issn = {1530-0293}, support = {//Wellcome Trust/United Kingdom ; 082372//Wellcome Trust/United Kingdom ; }, abstract = {OBJECTIVES: Adverse physiology and antibiotic exposure devastate the intestinal microbiome in critical illness. Time and cost implications limit the immediate clinical potential of microbial sequencing to identify or treat intestinal dysbiosis. Here, we examined whether metabolic profiling is a feasible method of monitoring intestinal dysbiosis in critically ill children.<br><br>DESIGN: Prospective multicenter cohort study.<br><br>SETTING: Three U.K.-based PICUs.<br><br>PATIENTS: Mechanically ventilated critically ill (n = 60) and age-matched healthy children (n = 55).<br><br>INTERVENTIONS: Collection of urine and fecal samples in children admitted to the PICU. A single fecal and urine sample was collected in healthy controls.<br><br>MEASUREMENTS AND MAIN RESULTS: Untargeted and targeted metabolic profiling using 1H-nuclear magnetic resonance spectroscopy and liquid chromatography-mass spectrometry or urine and fecal samples. This was integrated with analysis of fecal bacterial 16S ribosomal RNA profiles and clinical disease severity indicators. We observed separation of global urinary and fecal metabolic profiles in critically ill compared with healthy children. Urinary excretion of mammalian-microbial co-metabolites hippurate, 4-cresol sulphate, and formate were reduced in critical illness compared with healthy children. Reduced fecal excretion of short-chain fatty acids (including butyrate, propionate, and acetate) were observed in the patient cohort, demonstrating that these metabolites also distinguished between critical illness and health. Dysregulation of intestinal bile metabolism was evidenced by increased primary and reduced secondary fecal bile acid excretion. Fecal butyrate correlated with days free of intensive care at 30 days (r = 0.38; p = 0.03), while urinary formate correlated inversely with vasopressor requirement (r = -0.2; p = 0.037).<br><br>CONCLUSIONS: Disruption to the functional activity of the intestinal microbiome may result in worsening organ failure in the critically ill child. Profiling of bacterial metabolites in fecal and urine samples may support identification and treatment of intestinal dysbiosis in critical illness.}, }
@article {pmid31169073, year = {2019}, author = {Hsu, T and Gemmell, MR and Franzosa, EA and Berry, S and Mukhopadhya, I and Hansen, R and Michaud, M and Nielsen, H and Miller, WG and Nielsen, H and Bajaj-Elliott, M and Huttenhower, C and Garrett, WS and Hold, GL}, title = {Comparative genomics and genome biology of Campylobacter showae.}, journal = {Emerging microbes &amp; infections}, volume = {8}, number = {1}, pages = {827-840}, doi = {10.1080/22221751.2019.1622455}, pmid = {31169073}, issn = {2222-1751}, mesh = {Bacterial Proteins/genetics ; Campylobacter/classification/*genetics/isolation &amp; purification/pathogenicity ; Campylobacter Infections/*microbiology ; Crohn Disease/microbiology ; Gastroenteritis/microbiology ; *Genome, Bacterial ; Genomics ; Humans ; Phenotype ; Phylogeny ; Virulence ; Virulence Factors/genetics ; }, abstract = {Campylobacter showae a bacterium historically linked to gingivitis and periodontitis, has recently been associated with inflammatory bowel disease and colorectal cancer. Our aim was to generate genome sequences for new clinical C. showae strains and identify functional properties explaining their pathogenic potential. Eight C. showae genomes were assessed, four strains isolated from inflamed gut tissues from paediatric Crohn's disease patients, three strains from colonic adenomas, and one from a gastroenteritis patient stool. Genome assemblies were analyzed alongside the only 3 deposited C. showae genomes. The pangenome from these 11 strains consisted of 4686 unique protein families, and the core genome size was estimated at 1050 ± 15 genes with each new genome contributing an additional 206 ± 16 genes. Functional assays indicated that colonic strains segregated into 2 groups: adherent/invasive vs. non-adherent/non-invasive strains. The former possessed Type IV secretion machinery and S-layer proteins, while the latter contained Cas genes and other CRISPR associated proteins. Comparison of gene profiles with strains in Human Microbiome Project metagenomes showed that gut-derived isolates share genes specific to tongue dorsum and supragingival plaque counterparts. Our findings indicate that C. showae strains are phenotypically and genetically diverse and suggest that secretion systems may play an important role in virulence potential.}, }
@article {pmid31168910, year = {2019}, author = {Vress, D and Lim, B}, title = {Understanding the human microbiome: new icing on an old cake.}, journal = {BJOG : an international journal of obstetrics and gynaecology}, volume = {}, number = {}, pages = {}, doi = {10.1111/1471-0528.15816}, pmid = {31168910}, issn = {1471-0528}, }
@article {pmid31167634, year = {2019}, author = {LaPierre, N and Mangul, S and Alser, M and Mandric, I and Wu, NC and Koslicki, D and Eskin, E}, title = {MiCoP: microbial community profiling method for detecting viral and fungal organisms in metagenomic samples.}, journal = {BMC genomics}, volume = {20}, number = {Suppl 5}, pages = {423}, doi = {10.1186/s12864-019-5699-9}, pmid = {31167634}, issn = {1471-2164}, support = {R01 ES021801/ES/NIEHS NIH HHS/United States ; R01 MH101782/MH/NIMH NIH HHS/United States ; K25 HL080079/HL/NHLBI NIH HHS/United States ; P01 HL028481/HL/NHLBI NIH HHS/United States ; U01 DA024417/DA/NIDA NIH HHS/United States ; T32 EB016640/EB/NIBIB NIH HHS/United States ; R01 ES022282/ES/NIEHS NIH HHS/United States ; P01 HL030568/HL/NHLBI NIH HHS/United States ; R01 GM083198/GM/NIGMS NIH HHS/United States ; }, abstract = {BACKGROUND: High throughput sequencing has spurred the development of metagenomics, which involves the direct analysis of microbial communities in various environments such as soil, ocean water, and the human body. Many existing methods based on marker genes or k-mers have limited sensitivity or are too computationally demanding for many users. Additionally, most work in metagenomics has focused on bacteria and archaea, neglecting to study other key microbes such as viruses and eukaryotes.<br><br>RESULTS: Here we present a method, MiCoP (Microbiome Community Profiling), that uses fast-mapping of reads to build a comprehensive reference database of full genomes from viruses and eukaryotes to achieve maximum read usage and enable the analysis of the virome and eukaryome in each sample. We demonstrate that mapping of metagenomic reads is feasible for the smaller viral and eukaryotic reference databases. We show that our method is accurate on simulated and mock community data and identifies many more viral and fungal species than previously-reported results on real data from the Human Microbiome Project.<br><br>CONCLUSIONS: MiCoP is a mapping-based method that proves more effective than existing methods at abundance profiling of viruses and eukaryotes in metagenomic samples. MiCoP can be used to detect the full diversity of these communities. The code, data, and documentation are publicly available on GitHub at: https://github.com/smangul1/MiCoP .}, }
@article {pmid31164901, year = {2019}, author = {Tang, ZZ and Chen, G and Hong, Q and Huang, S and Smith, HM and Shah, RD and Scholz, M and Ferguson, JF}, title = {Multi-Omic Analysis of the Microbiome and Metabolome in Healthy Subjects Reveals Microbiome-Dependent Relationships Between Diet and Metabolites.}, journal = {Frontiers in genetics}, volume = {10}, number = {}, pages = {454}, doi = {10.3389/fgene.2019.00454}, pmid = {31164901}, issn = {1664-8021}, support = {15SDG24890015/AHA/American Heart Association-American Stroke Association/United States ; P30 DK058404/DK/NIDDK NIH HHS/United States ; U01 HL108636/HL/NHLBI NIH HHS/United States ; }, abstract = {The human microbiome has been associated with health status, and risk of disease development. While the etiology of microbiome-mediated disease remains to be fully elucidated, one mechanism may be through microbial metabolism. Metabolites produced by commensal organisms, including in response to host diet, may affect host metabolic processes, with potentially protective or pathogenic consequences. We conducted multi-omic phenotyping of healthy subjects (N = 136), in order to investigate the interaction between diet, the microbiome, and the metabolome in a cross-sectional sample. We analyzed the nutrient composition of self-reported diet (3-day food records and food frequency questionnaires). We profiled the gut and oral microbiome (16S rRNA) from stool and saliva, and applied metabolomic profiling to plasma and stool samples in a subset of individuals (N = 75). We analyzed these multi-omic data to investigate the relationship between diet, the microbiome, and the gut and circulating metabolome. On a global level, we observed significant relationships, particularly between long-term diet, the gut microbiome and the metabolome. Intake of plant-derived nutrients as well as consumption of artificial sweeteners were associated with significant differences in circulating metabolites, particularly bile acids, which were dependent on gut enterotype, indicating that microbiome composition mediates the effect of diet on host physiology. Our analysis identifies dietary compounds and phytochemicals that may modulate bacterial abundance within the gut and interact with microbiome composition to alter host metabolism.}, }
@article {pmid31164869, year = {2019}, author = {Belforte, FS and Fernandez, N and Tonín Monzón, F and Rosso, AD and Quesada, S and Cimolai, MC and Millán, A and Cerrone, GE and Frechtel, GD and Burcelin, R and Coluccio Leskow, F and Penas-Steinhardt, A}, title = {Getting to Know the Gut Microbial Diversity of Metropolitan Buenos Aires Inhabitants.}, journal = {Frontiers in microbiology}, volume = {10}, number = {}, pages = {965}, doi = {10.3389/fmicb.2019.00965}, pmid = {31164869}, issn = {1664-302X}, support = {T37 MD001452/MD/NIMHD NIH HHS/United States ; }, abstract = {In recent years, the field of immunology has been revolutionized by the growing understanding of the fundamental role of microbiota in the immune system function. The immune system has evolved to maintain a symbiotic relationship with these microbes. The aim of our study was to know in depth the uncharacterized metagenome of the Buenos Aires (BA) city population and its metropolitan area, being the second most populated agglomeration in the southern hemisphere. For this purpose, we evaluated 30 individuals (age: 35.23 ± 8.26 years and BMI: 23.91 ± 3.4 kg/m2), from the general population of BA. The hypervariable regions V3-V4 of the bacterial 16S gene was sequenced by MiSeq-Illumina system, obtaining 47526 ± 4718 sequences/sample. The dominant phyla were Bacteroidetes, Firmicutes, Proteobacteria, Verrucomicrobia, and Actinobacteria. Additionally, we compared the microbiota of BA with other westernized populations (Santiago de Chile, Rosario-Argentina, United States-Human-microbiome-project, Bologna-Italy) and the Hadza population of hunter-gatherers. The unweighted UniFrac clustered together all westernized populations, leaving the hunter-gatherer population from Hadza out. In particular, Santiago de Chile's population turns out to be the closest to BA's, principally due to the presence of Verrucomicrobiales of the genus Akkermansia. These microorganisms have been proposed as a hallmark of a healthy gut. Finally, westernized populations showed more abundant metabolism related KEEG pathways than hunter-gatherers, including carbohydrate metabolism (amino sugar and nucleotide sugar metabolism), amino acid metabolism (alanine, aspartate and glutamate metabolism), lipid metabolism, biosynthesis of secondary metabolites, and sulfur metabolism. These findings contribute to promote research and comparison of the microbiome in different human populations, in order to develop more efficient therapeutic strategies for the restoration of a healthy dialogue between host and environment.}, }
@article {pmid31163166, year = {2019}, author = {Granato, ET and Meiller-Legrand, TA and Foster, KR}, title = {The Evolution and Ecology of Bacterial Warfare.}, journal = {Current biology : CB}, volume = {29}, number = {11}, pages = {R521-R537}, doi = {10.1016/j.cub.2019.04.024}, pmid = {31163166}, issn = {1879-0445}, abstract = {Bacteria have evolved a wide range of mechanisms to harm and kill their competitors, including chemical, mechanical and biological weapons. Here we review the incredible diversity of bacterial weapon systems, which comprise antibiotics, toxic proteins, mechanical weapons that stab and pierce, viruses, and more. The evolution of bacterial weapons is shaped by many factors, including cell density and nutrient abundance, and how strains are arranged in space. Bacteria also employ a diverse range of combat behaviours, including pre-emptive attacks, suicidal attacks, and reciprocation (tit-for-tat). However, why bacteria carry so many weapons, and why they are so often used, remains poorly understood. By comparison with animals, we argue that the way that bacteria live - often in dense and genetically diverse communities - is likely to be key to their aggression as it encourages them to dig in and fight alongside their clonemates. The intensity of bacterial aggression is such that it can strongly affect communities, via complex coevolutionary and eco-evolutionary dynamics, which influence species over space and time. Bacterial warfare is a fascinating topic for ecology and evolution, as well as one of increasing relevance. Understanding how bacteria win wars is important for the goal of manipulating the human microbiome and other important microbial systems.}, }
@article {pmid31158845, year = {2019}, author = {Zimmermann, M and Zimmermann-Kogadeeva, M and Wegmann, R and Goodman, AL}, title = {Mapping human microbiome drug metabolism by gut bacteria and their genes.}, journal = {Nature}, volume = {570}, number = {7762}, pages = {462-467}, doi = {10.1038/s41586-019-1291-3}, pmid = {31158845}, issn = {1476-4687}, support = {DP2 GM105456/GM/NIGMS NIH HHS/United States ; R01 DK114793/DK/NIDDK NIH HHS/United States ; R35 GM118159/GM/NIGMS NIH HHS/United States ; U01 AI124275/AI/NIAID NIH HHS/United States ; }, abstract = {Individuals vary widely in their responses to medicinal drugs, which can be dangerous and expensive owing to treatment delays and adverse effects. Although increasing evidence implicates the gut microbiome in this variability, the molecular mechanisms involved remain largely unknown. Here we show, by measuring the ability of 76 human gut bacteria from diverse clades to metabolize 271 orally administered drugs, that many drugs are chemically modified by microorganisms. We combined high-throughput genetic analyses with mass spectrometry to systematically identify microbial gene products that metabolize drugs. These microbiome-encoded enzymes can directly and substantially affect intestinal and systemic drug metabolism in mice, and can explain the drug-metabolizing activities of human gut bacteria and communities on the basis of their genomic contents. These causal links between the gene content and metabolic activities of the microbiota connect interpersonal variability in microbiomes to interpersonal differences in drug metabolism, which has implications for medical therapy and drug development across multiple disease indications.}, }
@article {pmid31154251, year = {2019}, author = {Williams, DW and Gibson, G}, title = {Classification of individuals and the potential to detect sexual contact using the microbiome of the pubic region.}, journal = {Forensic science international. Genetics}, volume = {41}, number = {}, pages = {177-187}, doi = {10.1016/j.fsigen.2019.05.004}, pmid = {31154251}, issn = {1878-0326}, mesh = {Adult ; Aged ; Female ; *Genitalia ; Hair/*microbiology ; Humans ; Male ; *Microbiota ; Middle Aged ; Principal Component Analysis ; RNA, Ribosomal, 16S ; Sequence Analysis, RNA ; *Sexual Behavior ; Young Adult ; }, abstract = {In the absence of traditional DNA evidence, detection of sexual contact during intercourse is an important need for forensic analysis that might be addressed by studies of the pubic microbiome. Since 16S sequencing of various other body parts has shown that the microbiome may be individualizing, we reasoned that transfer of the assailant's microbiome to a victim might be detectable. Microbiome profiles were generated from pubic hairs and swabs taken from the pubic mound region of 12 couples and 19 singles, and evaluated for similarity over an average of four collection times with varying degrees of self-reported sexual activity. A model constructed using a Random Forest classifier was able to predict samples belonging to the same individual collected up to 6 months apart, demonstrating the stability of the pubic mound microbiome over this time frame. Couples were found to be significantly more similar to one another than to unrelated members of the opposite sex, in proportion to shared sexual activity. Further analyses using the Deblur method to assign operational taxonomic units (OTUs) establish that at least 10% of the victim's pubic microbiome must be derived from the attacker in order to detect transfer, but that single transfer events will not generally be discovered. Nevertheless, Bayesian SourceTracker software is shown to have potential to establish that sexual contact occurred when the assailant is known, or to exonerate suspects as contributors to a mixed microbiome. Our results establish limited potential of the pubic hair/pubic area microbiome as a tool for forensic associations.}, }
@article {pmid31142868, year = {2019}, author = {}, title = {After the Integrative Human Microbiome Project, what's next for the microbiome community?.}, journal = {Nature}, volume = {569}, number = {7758}, pages = {599}, doi = {10.1038/d41586-019-01674-w}, pmid = {31142868}, issn = {1476-4687}, }
@article {pmid31142863, year = {2019}, author = {Proctor, L}, title = {Priorities for the next 10 years of human microbiome research.}, journal = {Nature}, volume = {569}, number = {7758}, pages = {623-625}, doi = {10.1038/d41586-019-01654-0}, pmid = {31142863}, issn = {1476-4687}, }
@article {pmid31142855, year = {2019}, author = {Lloyd-Price, J and Arze, C and Ananthakrishnan, AN and Schirmer, M and Avila-Pacheco, J and Poon, TW and Andrews, E and Ajami, NJ and Bonham, KS and Brislawn, CJ and Casero, D and Courtney, H and Gonzalez, A and Graeber, TG and Hall, AB and Lake, K and Landers, CJ and Mallick, H and Plichta, DR and Prasad, M and Rahnavard, G and Sauk, J and Shungin, D and Vázquez-Baeza, Y and White, RA and ,  and Braun, J and Denson, LA and Jansson, JK and Knight, R and Kugathasan, S and McGovern, DPB and Petrosino, JF and Stappenbeck, TS and Winter, HS and Clish, CB and Franzosa, EA and Vlamakis, H and Xavier, RJ and Huttenhower, C}, title = {Multi-omics of the gut microbial ecosystem in inflammatory bowel diseases.}, journal = {Nature}, volume = {569}, number = {7758}, pages = {655-662}, doi = {10.1038/s41586-019-1237-9}, pmid = {31142855}, issn = {1476-4687}, support = {U54 DK102557/DK/NIDDK NIH HHS/United States ; U01 DK062413/DK/NIDDK NIH HHS/United States ; U01 DK097430/DK/NIDDK NIH HHS/United States ; P30 DK043351/DK/NIDDK NIH HHS/United States ; U54 DE023798/DE/NIDCR NIH HHS/United States ; R01 HG005969/HG/NHGRI NIH HHS/United States ; P01 DK046763/DK/NIDDK NIH HHS/United States ; UL1 TR001881/TR/NCATS NIH HHS/United States ; R24 DK110499/DK/NIDDK NIH HHS/United States ; }, abstract = {Inflammatory bowel diseases, which include Crohn's disease and ulcerative colitis, affect several million individuals worldwide. Crohn's disease and ulcerative colitis are complex diseases that are heterogeneous at the clinical, immunological, molecular, genetic, and microbial levels. Individual contributing factors have been the focus of extensive research. As part of the Integrative Human Microbiome Project (HMP2 or iHMP), we followed 132 subjects for one year each to generate integrated longitudinal molecular profiles of host and microbial activity during disease (up to 24 time points each; in total 2,965 stool, biopsy, and blood specimens). Here we present the results, which provide a comprehensive view of functional dysbiosis in the gut microbiome during inflammatory bowel disease activity. We demonstrate a characteristic increase in facultative anaerobes at the expense of obligate anaerobes, as well as molecular disruptions in microbial transcription (for example, among clostridia), metabolite pools (acylcarnitines, bile acids, and short-chain fatty acids), and levels of antibodies in host serum. Periods of disease activity were also marked by increases in temporal variability, with characteristic taxonomic, functional, and biochemical shifts. Finally, integrative analysis identified microbial, biochemical, and host factors central to this dysregulation. The study's infrastructure resources, results, and data, which are available through the Inflammatory Bowel Disease Multi'omics Database (http://ibdmdb.org), provide the most comprehensive description to date of host and microbial activities in inflammatory bowel diseases.}, }
@article {pmid31142853, year = {2019}, author = {, }, title = {The Integrative Human Microbiome Project.}, journal = {Nature}, volume = {569}, number = {7758}, pages = {641-648}, doi = {10.1038/s41586-019-1238-8}, pmid = {31142853}, issn = {1476-4687}, support = {R01 HD092415/HD/NICHD NIH HHS/United States ; UH3 AI083263/AI/NIAID NIH HHS/United States ; U54 DE023786/DE/NIDCR NIH HHS/United States ; UH2 AI083263/AI/NIAID NIH HHS/United States ; U54 HD080784/HD/NICHD NIH HHS/United States ; }, abstract = {The NIH Human Microbiome Project (HMP) has been carried out over ten years and two phases to provide resources, methods, and discoveries that link interactions between humans and their microbiomes to health-related outcomes. The recently completed second phase, the Integrative Human Microbiome Project, comprised studies of dynamic changes in the microbiome and host under three conditions: pregnancy and preterm birth; inflammatory bowel diseases; and stressors that affect individuals with prediabetes. The associated research begins to elucidate mechanisms of host-microbiome interactions under these conditions, provides unique data resources (at the HMP Data Coordination Center), and represents a paradigm for future multi-omic studies of the human microbiome.}, }
@article {pmid31142849, year = {2019}, author = {Fettweis, JM and Serrano, MG and Brooks, JP and Edwards, DJ and Girerd, PH and Parikh, HI and Huang, B and Arodz, TJ and Edupuganti, L and Glascock, AL and Xu, J and Jimenez, NR and Vivadelli, SC and Fong, SS and Sheth, NU and Jean, S and Lee, V and Bokhari, YA and Lara, AM and Mistry, SD and Duckworth, RA and Bradley, SP and Koparde, VN and Orenda, XV and Milton, SH and Rozycki, SK and Matveyev, AV and Wright, ML and Huzurbazar, SV and Jackson, EM and Smirnova, E and Korlach, J and Tsai, YC and Dickinson, MR and Brooks, JL and Drake, JI and Chaffin, DO and Sexton, AL and Gravett, MG and Rubens, CE and Wijesooriya, NR and Hendricks-Muñoz, KD and Jefferson, KK and Strauss, JF and Buck, GA}, title = {The vaginal microbiome and preterm birth.}, journal = {Nature medicine}, volume = {25}, number = {6}, pages = {1012-1021}, doi = {10.1038/s41591-019-0450-2}, pmid = {31142849}, issn = {1546-170X}, support = {R01 HD092415/HD/NICHD NIH HHS/United States ; UH3 AI083263/AI/NIAID NIH HHS/United States ; U54 DE023786/DE/NIDCR NIH HHS/United States ; UH2 AI083263/AI/NIAID NIH HHS/United States ; U54 HD080784/HD/NICHD NIH HHS/United States ; }, mesh = {Adult ; African Americans ; Biodiversity ; Cohort Studies ; Cytokines/metabolism ; Female ; Host Microbial Interactions/immunology ; Humans ; Infant, Newborn ; Inflammation Mediators/metabolism ; Longitudinal Studies ; Metagenomics ; *Microbiota/genetics/immunology ; Premature Birth/etiology/immunology/*microbiology ; Risk Factors ; United States ; Vagina/immunology/*microbiology ; Young Adult ; }, abstract = {The incidence of preterm birth exceeds 10% worldwide. There are significant disparities in the frequency of preterm birth among populations within countries, and women of African ancestry disproportionately bear the burden of risk in the United States. In the present study, we report a community resource that includes 'omics' data from approximately 12,000 samples as part of the integrative Human Microbiome Project. Longitudinal analyses of 16S ribosomal RNA, metagenomic, metatranscriptomic and cytokine profiles from 45 preterm and 90 term birth controls identified harbingers of preterm birth in this cohort of women predominantly of African ancestry. Women who delivered preterm exhibited significantly lower vaginal levels of Lactobacillus crispatus and higher levels of BVAB1, Sneathia amnii, TM7-H1, a group of Prevotella species and nine additional taxa. The first representative genomes of BVAB1 and TM7-H1 are described. Preterm-birth-associated taxa were correlated with proinflammatory cytokines in vaginal fluid. These findings highlight new opportunities for assessment of the risk of preterm birth.}, }
@article {pmid31140702, year = {2019}, author = {Varoni, EM and Bavarian, R and Robledo-Sierra, J and Porat Ben-Amy, D and Wade, WG and Paster, B and Kerr, R and Peterson, DE and Frandsen Lau, E}, title = {World Workshop on Oral Medicine VII: Targeting the microbiome for oral medicine specialists-Part 1. A methodological guide.}, journal = {Oral diseases}, volume = {25 Suppl 1}, number = {}, pages = {12-27}, doi = {10.1111/odi.13063}, pmid = {31140702}, issn = {1601-0825}, support = {Steering guidance regarding additional text for ac//World Workshop on Oral Medicine VII/ ; }, abstract = {Advances in high-throughput sequencing technologies have allowed for a rapid increase in knowledge about the human microbiome in both healthy and diseased states, which is expected to increase our understanding of multifactorial diseases. The World Workshop on Oral Medicine VII chose the microbiome as one of its topics of focus. Part 1 of this review provides updated knowledge in the field of microbiome research, describes the advantages and disadvantages of currently available sequencing technologies, and proposes a seven-step &quot;recipe&quot; for designing and performing studies that is supported by contemporary evidence. Part 2 of this review in a companion paper discusses the results of high-throughput sequencing studies published to date on the microbiota associated with oral mucosal diseases. The goal of this collective enterprise is to encourage more oral medicine specialists to become engaged in multidisciplinary collaborations to investigate the role of the microbiome in relation to oral diseases, which could potentially lead to enhanced diagnosis, risk assessment and treatment of these patients.}, }
@article {pmid31133693, year = {2019}, author = {Gilbert, JA and Lynch, SV}, title = {Community ecology as a framework for human microbiome research.}, journal = {Nature medicine}, volume = {25}, number = {6}, pages = {884-889}, doi = {10.1038/s41591-019-0464-9}, pmid = {31133693}, issn = {1546-170X}, mesh = {Biodiversity ; Computational Biology ; Ecosystem ; Host Microbial Interactions ; Humans ; *Microbiota ; Models, Biological ; Research ; }, abstract = {The field of human microbiome research has revealed the intimate co-association of humans with diverse communities of microbes in various habitats in the human body, and the necessity of these microbes for the maintenance of human health. Microbial heterogeneity between humans and across spatial and temporal gradients requires multidimensional datasets and a unifying set of theories and statistical tools to analyze the human microbiome and fully realize the potential of this field. Here we consider the utility of community ecology as a framework for the interrogation and interpretation of the human microbiome.}, }
@article {pmid31123962, year = {2019}, author = {Pulkkinen, E and Wicklund, A and Oduor, JMO and Skurnik, M and Kiljunen, S}, title = {Characterization of vB_ApiM_fHyAci03, a novel lytic bacteriophage that infects clinical Acinetobacter strains.}, journal = {Archives of virology}, volume = {164}, number = {8}, pages = {2197-2199}, doi = {10.1007/s00705-019-04284-z}, pmid = {31123962}, issn = {1432-8798}, support = {TYH2018228//Special state subsidy for health science research/ ; TYH2015411//Special state subsidy for health science research/ ; }, mesh = {Acinetobacter/*virology ; Bacteriophages/*genetics ; DNA, Viral/genetics ; Genome, Viral/genetics ; Host Specificity/genetics ; Myoviridae/genetics ; Phylogeny ; }, abstract = {We present here the isolation and characterization of Acinetobacter pittii phage vB_ApiM_fHyAci03 (fHyAci03), which belongs to the family Myoviridae. The fHyAci03 genome was found to be 165,975 bp in length and predicted to contain 255 genes. While the whole genome was 92.4% identical to Acinetobacter baumannii phage KARL-1, phylogenetic analysis based on phage long distal tail fiber amino acid sequences assigned fHyAci03 and KARL-1 to different subclusters, reflecting their different host species. Together with phylogenetic analysis, genome comparisons indicated that fHyAci03 is a novel member of the subfamily Tevenvirinae. Host range experiments revealed that fHyAci03 could infect two clinical strains of Acinetobacter nosocomialis and six clinical strains of A. pittii. Thus, fHyAci03 is a novel lytic phage that infects clinical Acinetobacter strains and represents a potential new candidate to be used in phage therapy.}, }
@article {pmid31123296, year = {2019}, author = {Virtanen, S and Rantsi, T and Virtanen, A and Kervinen, K and Nieminen, P and Kalliala, I and Salonen, A}, title = {Vaginal Microbiota Composition Correlates Between Pap Smear Microscopy and Next Generation Sequencing and Associates to Socioeconomic Status.}, journal = {Scientific reports}, volume = {9}, number = {1}, pages = {7750}, doi = {10.1038/s41598-019-44157-8}, pmid = {31123296}, issn = {2045-2322}, support = {TYH2014310/1179003//Helsingin ja Uudenmaan Sairaanhoitopiiri (Helsinki University Central Hospital)/ ; TYH2014310/1179003//Helsingin ja Uudenmaan Sairaanhoitopiiri (Helsinki University Central Hospital)/ ; TYH2014310/1179003//Helsingin ja Uudenmaan Sairaanhoitopiiri (Helsinki University Central Hospital)/ ; }, abstract = {Recent research on vaginal microbiota relies on high throughput sequencing while microscopic methods have a long history in clinical use. We investigated the correspondence between microscopic findings of Pap smears and the vaginal microbiota composition determined by next generation sequencing among 50 asymptomatic women. Both methods produced coherent results regarding the distinction between Lactobacillus-dominant versus mixed microbiota, reassuring gynaecologists for the use of Pap smear or wet mount microscopy for rapid evaluation of vaginal bacteria as part of diagnosis. Cytologic findings identified women with bacterial vaginosis and revealed that cytolysis of vaginal epithelial cells is associated to Lactobacillus crispatus-dominated microbiota. Education and socio-economic status were associated to the vaginal microbiota variation. Our results highlight the importance of including socio-economic status as a co-factor in future vaginal microbiota studies.}, }
@article {pmid31122279, year = {2019}, author = {Ross, AA and Rodrigues Hoffmann, A and Neufeld, JD}, title = {The skin microbiome of vertebrates.}, journal = {Microbiome}, volume = {7}, number = {1}, pages = {79}, doi = {10.1186/s40168-019-0694-6}, pmid = {31122279}, issn = {2049-2618}, abstract = {The skin constitutes the primary physical barrier between vertebrates and their external environment. Characterization of skin microorganisms is essential for understanding how a host evolves in association with its microbial symbionts, modeling immune system development, diagnosing illnesses, and exploring the origins of potential zoonoses that affect humans. Although many studies have characterized the human microbiome with culture-independent techniques, far less is known about the skin microbiome of other mammals, amphibians, birds, fish, and reptiles. The aim of this review is to summarize studies that have leveraged high-throughput sequencing to better understand the skin microorganisms that associate with members of classes within the subphylum Vertebrata. Specifically, links will be explored between the skin microbiome and vertebrate characteristics, including geographic location, biological sex, animal interactions, diet, captivity, maternal transfer, and disease. Recent literature on parallel patterns between host evolutionary history and their skin microbial communities, or phylosymbiosis, will also be analyzed. These factors must be considered when designing future microbiome studies to ensure that the conclusions drawn from basic research translate into useful applications, such as probiotics and successful conservation strategies for endangered and threatened animals.}, }
@article {pmid31121812, year = {2019}, author = {Biesiekierski, JR and Jalanka, J and Staudacher, HM}, title = {Can Gut Microbiota Composition Predict Response to Dietary Treatments?.}, journal = {Nutrients}, volume = {11}, number = {5}, pages = {}, doi = {10.3390/nu11051134}, pmid = {31121812}, issn = {2072-6643}, abstract = {Dietary intervention is a challenge in clinical practice because of inter-individual variability in clinical response. Gut microbiota is mechanistically relevant for a number of disease states and consequently has been incorporated as a key variable in personalised nutrition models within the research context. This paper aims to review the evidence related to the predictive capacity of baseline microbiota for clinical response to dietary intervention in two specific health conditions, namely, obesity and irritable bowel syndrome (IBS). Clinical trials and larger predictive modelling studies were identified and critically evaluated. The findings reveal inconsistent evidence to support baseline microbiota as an accurate predictor of weight loss or glycaemic response in obesity, or as a predictor of symptom improvement in irritable bowel syndrome, in dietary intervention trials. Despite advancement in quantification methodologies, research in this area remains challenging and larger scale studies are needed until personalised nutrition is realistically achievable and can be translated to clinical practice.}, }
@article {pmid31117024, year = {2019}, author = {Amato, KR}, title = {Missing Links: the Role of Primates in Understanding the Human Microbiome.}, journal = {mSystems}, volume = {4}, number = {3}, pages = {}, doi = {10.1128/mSystems.00165-19}, pmid = {31117024}, issn = {2379-5077}, abstract = {The gut microbiome can influence host energy balances and metabolic programming. While this information is valuable in a disease context, it also has important implications for understanding host energetics from an ecological and evolutionary perspective. Here I argue that gut microbial influences on host life history-the timing of events that make up an organism's life-are an overlooked but robust area of study given that variation in life history is linked directly to host energetic budgets and allocation patterns. Additionally, while cultural influences on life history complicate the exploration of these links in humans, nonhuman primates represent an alternative system in which more robust associations can be made. By integrating human and nonhuman primate microbiome research within the context of life history theory, we will be able to more effectively pinpoint microbial contributions to host phenotypes. This information will improve our understanding of host-microbe interactions in health and disease and will transform the fields of ecology and evolution more generally.}, }
@article {pmid31113222, year = {2019}, author = {Lew, KN and Starkweather, A and Cong, X and Judge, M}, title = {A Mechanistic Model of Gut-Brain Axis Perturbation and High-Fat Diet Pathways to Gut Microbiome Homeostatic Disruption, Systemic Inflammation, and Type 2 Diabetes.}, journal = {Biological research for nursing}, volume = {21}, number = {4}, pages = {384-399}, doi = {10.1177/1099800419849109}, pmid = {31113222}, issn = {1552-4175}, abstract = {Type 2 diabetes (T2D) is a highly prevalent metabolic disease, affecting nearly 10% of the American population. Although the etiopathogenesis of T2D remains poorly understood, advances in DNA sequencing technologies have allowed for sophisticated interrogation of the human microbiome, providing insight into the role of the gut microbiome in the development and progression of T2D. An emerging body of research reveals that gut-brain axis (GBA) perturbations and a high-fat diet (HFD), along with other modifiable and nonmodifiable risk factors, contribute to gut microbiome homeostatic imbalance. Homeostatic imbalance or disruption increases gut wall permeability and facilitates translocation of endotoxins (lipopolysaccharides) into the circulation with resultant systemic inflammation. Chronic, low-grade systemic inflammation ensues with pro-inflammatory pathways activated, contributing to obesity, insulin resistance (IR), pancreatic β-cell decline, and, thereby, T2D. While GBA perturbations and HFD are implicated in provoking these conditions, prior mechanistic models have tended to examine HFD and GBA pathways exclusively without considering their shared pathways to T2D. Addressing this gap, this article proposes a mechanistic model informed by animal and human studies to advance scientific understanding of (1) modifiable and nonmodifiable risk factors for gut microbiome homeostatic disruption, (2) HFD and GBA pathways contributing to homeostatic disruption, and (3) shared GBA and HFD pro-inflammatory pathways to obesity, IR, β-cell decline, and T2D. The proposed mechanistic model, based on the extant literature, proposes a framework for studying the complex relationships of the gut microbiome to T2D to advance study in this promising area of research.}, }
@article {pmid31107866, year = {2019}, author = {Mainali, K and Bewick, S and Vecchio-Pagan, B and Karig, D and Fagan, WF}, title = {Detecting interaction networks in the human microbiome with conditional Granger causality.}, journal = {PLoS computational biology}, volume = {15}, number = {5}, pages = {e1007037}, doi = {10.1371/journal.pcbi.1007037}, pmid = {31107866}, issn = {1553-7358}, abstract = {Human microbiome research is rife with studies attempting to deduce microbial correlation networks from sequencing data. Standard correlation and/or network analyses may be misleading when taken as an indication of taxon interactions because &quot;correlation is neither necessary nor sufficient to establish causation&quot;; environmental filtering can lead to correlation between non-interacting taxa. Unfortunately, microbial ecologists have generally used correlation as a proxy for causality although there is a general consensus about what constitutes a causal relationship: causes both precede and predict effects. We apply one of the first causal models for detecting interactions in human microbiome samples. Specifically, we analyze a long duration, high resolution time series of the human microbiome to decipher the networks of correlation and causation of human-associated microbial genera. We show that correlation is not a good proxy for biological interaction; we observed a weak negative relationship between correlation and causality. Strong interspecific interactions are disproportionately positive, whereas almost all strong intraspecific interactions are negative. Interestingly, intraspecific interactions also appear to act at a short timescale causing vast majority of the effects within 1-3 days. We report how different taxa are involved in causal relationships with others, and show that strong interspecific interactions are rarely conserved across two body sites whereas strong intraspecific interactions are much more conserved, ranging from 33% between the gut and right-hand to 70% between the two hands. Therefore, in the absence of guiding assumptions about ecological interactions, Granger causality and related techniques may be particularly helpful for understanding the driving factors governing microbiome composition and structure.}, }
@article {pmid31106972, year = {2019}, author = {Ogunrinde, E and Zhou, Z and Luo, Z and Alekseyenko, A and Li, QZ and Macedo, D and Kamen, DL and Oates, JC and Gilkeson, GS and Jiang, W}, title = {A link between plasma microbial translocation, microbiome, and autoantibody development in first-degree relatives of systemic lupus erythematosus patients.}, journal = {Arthritis &amp; rheumatology (Hoboken, N.J.)}, volume = {}, number = {}, pages = {}, doi = {10.1002/art.40935}, pmid = {31106972}, issn = {2326-5205}, support = {P30 AR072582/AR/NIAMS NIH HHS/United States ; U54 CA210962/CA/NCI NIH HHS/United States ; }, abstract = {OBJECTIVE: Systemic lupus erythematosus (SLE) is characterized by antibody production against self-antigens. However, the events underlying autoantibody formation in SLE remains unclear. This study investigated the role of plasma autoantibody levels, microbial translocation, and the microbiome in SLE.<br><br>METHODS: Plasma samples from two cohorts, one with 18 unrelated healthy controls (UHCs) and 18 first-degree relatives (FDRs) and the other with 19 healthy controls and 21 SLE patients were assessed for autoantibody levels by autoantigen microarrays, lipopolysaccharide (LPS) levels by limulus amebocyte assay and microbiome composition by microbial 16S rDNA sequencing.<br><br>RESULTS: FDRs and SLE patients exhibited increased plasma autoantibodies compared to their control groups. Parents and children of lupus patients exhibited elevated plasma LPS levels in comparison to controls (p = 0.02). Plasma LPS levels positively correlated with plasma anti-dsDNA IgG levels in FDRs (r=0.51, p=0.03) but not in SLE patients. Circulating microbiome analysis revealed that FDRs (Observed species, p=0.004; Chao1 index, p=0.005) but not patients had significantly reduced microbiome diversity compared to their controls. The majority of differentially abundant bacteria identified between UHCs and FDRs were in the Firmicutes phylum, while bacteria from several different phyla were identified between HCs and SLE patients. Bacteria in the Paenibacillus genus was the only overlapping differentially abundant bacteria in both cohorts, and it was reduced in FDRs (p.adj = 2.13 x 10-12) and SLE patients (p.adj = 0.008) but elevated in controls.<br><br>CONCLUSIONS: These results indicate a possible role for plasma microbial translocation and microbiome composition in influencing autoantibody development in SLE. This article is protected by copyright. All rights reserved.}, }
@article {pmid31102759, year = {2019}, author = {Levi Mortera, S and Soggiu, A and Vernocchi, P and Del Chierico, F and Piras, C and Carsetti, R and Marzano, V and Britti, D and Urbani, A and Roncada, P and Putignani, L}, title = {Metaproteomic investigation to assess gut microbiota shaping in newborn mice: A combined taxonomic, functional and quantitative approach.}, journal = {Journal of proteomics}, volume = {203}, number = {}, pages = {103378}, doi = {10.1016/j.jprot.2019.103378}, pmid = {31102759}, issn = {1876-7737}, abstract = {Breastfeeding is nowadays known to be one of the most critical factors contributing to the development of an efficient immune system. In the last decade, a consistent number of pieces of evidence demonstrated the relationship between a healthy organism and its gut microbiota. However, this link is still not fully understood and requires further investigation. We recently adopted a murine model to describe the impact of either maternal milk or parental genetic background, on the composition of the gut microbial population in the first weeks of life. A metaproteomic approach to such complex environments is a big challenge that requires a strong effort in both data production and analysis, including the set-up of dedicated multitasking bioinformatics pipelines. Herein we present an LC-MS/MS based investigation to monitor mouse gut microbiota in the early life, aiming at characterizing its functions and metabolic activities together with a taxonomic description in terms of operational taxonomic units. We provided a quantitative evaluation of bacterial metaproteins, taking into account differential expression results in relation to the functional and taxonomic classification, particularly with proteins from orthologues groups. This allowed the reduction of the bias arising from the presence of a high number of shared peptides, and proteins, among different bacterial species. We also focused on host mucosal proteome and its modulation, according to different microbiota composition. SIGNIFICANCE: This paper would represent a reference work for investigations on gut microbiota in early life, from both a microbiological and a functional proteomic point of view. We focused on the shaping of the mouse gut microbiota in dependence on the feeding modality, defining a reliable taxonomic description, highlighting some functional characteristics of the microbial community, and performing a first quantitative evaluation by data independent analysis in metaproteomics.}, }
@article {pmid31093759, year = {2019}, author = {Oduor, JMO and Kiljunen, S and Kadija, E and Mureithi, MW and Nyachieo, A and Skurnik, M}, title = {Genomic characterization of four novel Staphylococcus myoviruses.}, journal = {Archives of virology}, volume = {164}, number = {8}, pages = {2171-2173}, doi = {10.1007/s00705-019-04267-0}, pmid = {31093759}, issn = {1432-8798}, support = {28.06.2017 (Decision letter date)//International Society for Infectious Diseases/European Society of Clinical Microbiology and Infectious Diseases (ISID/ESCMID) Fellowships/ ; TM-17- 10301//EDUFI FELLOWSHIP (Finland)/ ; TM-18- 10752//EDUFI FELLOWSHIP (Finland)/ ; 14.10.2016 (Decision letter date)//Jane ja Aatos Erkon Säätiö (FI)/ ; }, mesh = {DNA, Viral/genetics ; Genome, Viral/genetics ; Genomics/methods ; Myoviridae/*genetics ; Phylogeny ; Sequence Analysis, DNA/methods ; Staphylococcus/*genetics ; Staphylococcus Phages/genetics ; }, abstract = {We report here the annotation of the complete genomes of four novel lytic Staphylococcus phages; Stab20, Stab21, Stab22 and Stab23. These phages have double-stranded DNA genomes ranging between 153,338 and 155,962 bp in size with terminal repeats of 10,814-12,304 bp. The genome analysis suggests that they represent new phage species within the genus Kayvirus in the subfamily Twortvirinae of the family Herelleviridae.}, }
@article {pmid31092590, year = {2019}, author = {Scott, AJ and Alexander, JL and Merrifield, CA and Cunningham, D and Jobin, C and Brown, R and Alverdy, J and O'Keefe, SJ and Gaskins, HR and Teare, J and Yu, J and Hughes, DJ and Verstraelen, H and Burton, J and O'Toole, PW and Rosenberg, DW and Marchesi, JR and Kinross, JM}, title = {International Cancer Microbiome Consortium consensus statement on the role of the human microbiome in carcinogenesis.}, journal = {Gut}, volume = {68}, number = {9}, pages = {1624-1632}, doi = {10.1136/gutjnl-2019-318556}, pmid = {31092590}, issn = {1468-3288}, support = {C42378/A25637/CRUK_/Cancer Research UK/United Kingdom ; /DH_/Department of Health/United Kingdom ; }, abstract = {OBJECTIVE: In this consensus statement, an international panel of experts deliver their opinions on key questions regarding the contribution of the human microbiome to carcinogenesis.<br><br>DESIGN: International experts in oncology and/or microbiome research were approached by personal communication to form a panel. A structured, iterative, methodology based around a 1-day roundtable discussion was employed to derive expert consensus on key questions in microbiome-oncology research.<br><br>RESULTS: Some 18 experts convened for the roundtable discussion and five key questions were identified regarding: (1) the relevance of dysbiosis/an altered gut microbiome to carcinogenesis; (2) potential mechanisms of microbiota-induced carcinogenesis; (3) conceptual frameworks describing how the human microbiome may drive carcinogenesis; (4) causation versus association; and (5) future directions for research in the field.The panel considered that, despite mechanistic and supporting evidence from animal and human studies, there is currently no direct evidence that the human commensal microbiome is a key determinant in the aetiopathogenesis of cancer. The panel cited the lack of large longitudinal, cohort studies as a principal deciding factor and agreed that this should be a future research priority. However, while acknowledging gaps in the evidence, expert opinion was that the microbiome, alongside environmental factors and an epigenetically/genetically vulnerable host, represents one apex of a tripartite, multidirectional interactome that drives carcinogenesis.<br><br>CONCLUSION: Data from longitudinal cohort studies are needed to confirm the role of the human microbiome as a key driver in the aetiopathogenesis of cancer.}, }
@article {pmid31091091, year = {2019}, author = {Bui, TPN and Troise, AD and Fogliano, V and de Vos, WM}, title = {Anaerobic Degradation of N-ε-Carboxymethyllysine, a Major Glycation End-Product, by Human Intestinal Bacteria.}, journal = {Journal of agricultural and food chemistry}, volume = {67}, number = {23}, pages = {6594-6602}, doi = {10.1021/acs.jafc.9b02208}, pmid = {31091091}, issn = {1520-5118}, mesh = {Adult ; Anaerobiosis ; Bacteria/classification/genetics/isolation &amp; purification/*metabolism ; Colon/*microbiology ; Feces/microbiology ; *Gastrointestinal Microbiome ; Glycation End Products, Advanced/chemistry/*metabolism ; Glycosylation ; Humans ; Infant ; Lysine/*analogs &amp; derivatives/chemistry/metabolism ; }, abstract = {Modifications of lysine contribute to the amount of dietary advanced glycation end-products reaching the colon. However, little is known about the ability of intestinal bacteria to metabolize dietary N-ε-carboxymethyllysine (CML). Successive transfers of fecal microbiota in growth media containing CML were used to identify and isolate species able to metabolize CML under anaerobic conditions. From our study, only donors exposed to processed foods degraded CML, and anaerobic bacteria enrichments from two of them used 77 and 100% of CML. Oscillibacter and Cloacibacillus evryensis increased in the two donors after the second transfer, highlighting that the bacteria from these taxa could be candidates for anaerobic CML degradation. A tentative identification of CML metabolites produced by a pure culture of Cloacibacillus evryensis was performed by mass spectrometry: carboxymethylated biogenic amines and carboxylic acids were identified as CML degradation products. The study confirmed the ability of intestinal bacteria to metabolize CML under anoxic conditions.}, }
@article {pmid31090586, year = {2019}, author = {Chernikova, D and Yuan, I and Shaker, M}, title = {Prevention of allergy with diverse and healthy microbiota: an update.}, journal = {Current opinion in pediatrics}, volume = {31}, number = {3}, pages = {418-425}, doi = {10.1097/MOP.0000000000000766}, pmid = {31090586}, issn = {1531-698X}, abstract = {PURPOSE OF REVIEW: Microbiota consist of symbiotic microscopic neighbors that interact on and within our bodies in diverse and incompletely understood ways throughout our lifetime. Though various associations with allergic disease have been described, clear effective therapeutic interventions to prevent allergy have been elusive.<br><br>RECENT FINDINGS: The human microbiome is influenced by multiple factors, including: mode of infant delivery (vaginal vs. cesarean section), breastfeeding, diet, presence of siblings and pets, exposure to antibiotics and other medications (particularly antacids), lifestyle, and developmental context. Microbial species promoting atopic responses and tolerance have been described. Specific microbiota likely act through distinct metabolic pathways to promote the health of their human hosts, optimally directing the developing immune system away from pro-allergic, Th2-dominated responses to more T-regulatory-influenced behaviors.<br><br>SUMMARY: Evidence suggests that specific healthy infant microbiome signatures may influence development of some components of the allergic march of childhood by decreasing atopic dermatitis, asthma, and food allergy. Further understanding of factors that influence healthy microbiota may lead to specific strategies tailored for early intervention and disease prevention.}, }
@article {pmid31076500, year = {2019}, author = {Ahmed, B and Cox, MJ and Cuthbertson, L}, title = {Growing up with your airway microbiota: a risky business.}, journal = {Thorax}, volume = {74}, number = {6}, pages = {525-526}, doi = {10.1136/thoraxjnl-2019-213162}, pmid = {31076500}, issn = {1468-3296}, }
@article {pmid31076212, year = {2019}, author = {Beghini, F and Renson, A and Zolnik, CP and Geistlinger, L and Usyk, M and Moody, TU and Thorpe, L and Dowd, JB and Burk, R and Segata, N and Jones, HE and Waldron, L}, title = {Tobacco exposure associated with oral microbiota oxygen utilization in the New York City Health and Nutrition Examination Study.}, journal = {Annals of epidemiology}, volume = {34}, number = {}, pages = {18-25.e3}, doi = {10.1016/j.annepidem.2019.03.005}, pmid = {31076212}, issn = {1873-2585}, support = {R21 AI121784/AI/NIAID NIH HHS/United States ; U24 CA180996/CA/NCI NIH HHS/United States ; }, abstract = {PURPOSE: The effect of tobacco exposure on the oral microbiome has not been established.<br><br>METHODS: We performed amplicon sequencing of the 16S ribosomal RNA gene V4 variable region to estimate bacterial community characteristics in 259 oral rinse samples, selected based on self-reported smoking and serum cotinine levels, from the 2013-2014 New York City Health and Nutrition Examination Study. We identified differentially abundant operational taxonomic units (OTUs) by primary and secondhand tobacco exposure, and used &quot;microbe set enrichment analysis&quot; to assess shifts in microbial oxygen utilization.<br><br>RESULTS: Cigarette smoking was associated with depletion of aerobic OTUs (Enrichment Score test statistic ES = -0.75, P = .002) with a minority (29%) of aerobic OTUs enriched in current smokers compared with never smokers. Consistent shifts in the microbiota were observed for current cigarette smokers as for nonsmokers with secondhand exposure as measured by serum cotinine levels. Differential abundance findings were similar in crude and adjusted analyses.<br><br>CONCLUSIONS: Results support a plausible link between tobacco exposure and shifts in the oral microbiome at the population level through three lines of evidence: (1) a shift in microbiota oxygen utilization associated with primary tobacco smoke exposure; (2) consistency of abundance fold changes associated with current smoking and shifts along the gradient of secondhand smoke exposure among nonsmokers; and (3) consistency after adjusting for a priori hypothesized confounders.}, }
@article {pmid31070803, year = {2019}, author = {Rodricks, J and Huang, Y and Mantus, E and Shubat, P}, title = {Do Interactions Between Environmental Chemicals and the Human Microbiome Need to Be Considered in Risk Assessments?.}, journal = {Risk analysis : an official publication of the Society for Risk Analysis}, volume = {}, number = {}, pages = {}, doi = {10.1111/risa.13316}, pmid = {31070803}, issn = {1539-6924}, abstract = {One of the most dynamic and fruitful areas of current health-related research concerns the various roles of the human microbiome in disease. Evidence is accumulating that interactions between substances in the environment and the microbiome can affect risks of disease, in both beneficial and adverse ways. Although most of the research has concerned the roles of diet and certain pharmaceutical agents, there is increasing interest in the possible roles of environmental chemicals. Chemical risk assessment has, to date, not included consideration of the influence of the microbiome. We suggest that failure to consider the possible roles of the microbiome could lead to significant error in risk assessment results. Our purpose in this commentary is to summarize some of the evidence supporting our hypothesis and to urge the risk assessment community to begin considering and influencing how results from microbiome-related research could be incorporated into chemical risk assessments. An additional emphasis in our commentary concerns the distinct possibility that research on chemical-microbiome interactions will also reduce some of the significant uncertainties that accompany current risk assessments. Of particular interest is evidence suggesting that the microbiome has an influence on variability in disease risk across populations and (of particular interest to chemical risk) in animal and human responses to chemical exposure. The possible explanatory power of the microbiome regarding sources of variability could reduce what might be the most significant source of uncertainty in chemical risk assessment.}, }
@article {pmid31064829, year = {2019}, author = {Zhu, L and Zou, Q and Cao, X and Cronan, JE}, title = {Enterococcus faecalis Encodes an Atypical Auxiliary Acyl Carrier Protein Required for Efficient Regulation of Fatty Acid Synthesis by Exogenous Fatty Acids.}, journal = {mBio}, volume = {10}, number = {3}, pages = {}, doi = {10.1128/mBio.00577-19}, pmid = {31064829}, issn = {2150-7511}, support = {R01 AI015650/AI/NIAID NIH HHS/United States ; R37 AI015650/AI/NIAID NIH HHS/United States ; }, mesh = {Acyl Carrier Protein/genetics/*metabolism ; Bacterial Proteins/genetics/*metabolism ; Biosynthetic Pathways ; Enterococcus faecalis/genetics/*metabolism ; Fatty Acids/*metabolism ; *Gene Expression Regulation, Bacterial ; Lipid Metabolism ; Operon ; }, abstract = {Acyl carrier proteins (ACPs) play essential roles in the synthesis of fatty acids and transfer of long fatty acyl chains into complex lipids. The Enterococcus faecalis genome contains two annotated acp genes, called acpA and acpB AcpA is encoded within the fatty acid synthesis (fab) operon and appears essential. In contrast, AcpB is an atypical ACP, having only 30% residue identity with AcpA, and is not essential. Deletion of acpB has no effect on E. faecalis growth or de novo fatty acid synthesis in media lacking fatty acids. However, unlike the wild-type strain, where growth with oleic acid resulted in almost complete blockage of de novo fatty acid synthesis, the ΔacpB strain largely continued de novo fatty acid synthesis under these conditions. Blockage in the wild-type strain is due to repression of fab operon transcription, leading to levels of fatty acid synthetic proteins (including AcpA) that are insufficient to support de novo synthesis. Transcription of the fab operon is regulated by FabT, a repressor protein that binds DNA only when it is bound to an acyl-ACP ligand. Since AcpA is encoded in the fab operon, its synthesis is blocked when the operon is repressed and acpA thus cannot provide a stable supply of ACP for synthesis of the acyl-ACP ligand required for DNA binding by FabT. In contrast to AcpA, acpB transcription is unaffected by growth with exogenous fatty acids and thus provides a stable supply of ACP for conversion to the acyl-ACP ligand required for repression by FabT. Indeed, ΔacpB and ΔfabT strains have essentially the same de novo fatty acid synthesis phenotype in oleic acid-grown cultures, which argues that neither strain can form the FabT-acyl-ACP repression complex. Finally, acylated derivatives of both AcpB and AcpA were substrates for the E. faecalis enoyl-ACP reductases and for E. faecalis PlsX (acyl-ACP; phosphate acyltransferase).IMPORTANCE AcpB homologs are encoded by many, but not all, lactic acid bacteria (Lactobacillales), including many members of the human microbiome. The mechanisms regulating fatty acid synthesis by exogenous fatty acids play a key role in resistance of these bacteria to those antimicrobials targeted at fatty acid synthesis enzymes. Defective regulation can increase resistance to such inhibitors and also reduce pathogenesis.}, }
@article {pmid31059117, year = {2019}, author = {Jagodzinski, A and Zielinska, E and Laczmanski, L and Hirnle, L}, title = {The early years of life. Are they influenced by our microbiome?.}, journal = {Ginekologia polska}, volume = {90}, number = {4}, pages = {228-232}, doi = {10.5603/GP.2019.0041}, pmid = {31059117}, issn = {2543-6767}, abstract = {Human microbiome contains the genetic pool of bacteria and other microbes such as Achaea, fungi and viruses inhabiting the human body. It holds an immense potential to affect both physiological and pathological processes. The microbiome's composition can be defined in detail by analyzing ribosomal 16S rRNA and metagenomic tests. Recent increases in cesar- ean sections, the use of antibiotics during pregnancy, the increasing amount of prematurely born children and changes in infant nutrition have an impact on the microbiome forming process. A correlation between the bowel microbiome's com- position and the occurrence of certain diseases, especially inflammatory bowel diseases (IBD), asthma and type 1 diabetes has been demonstrated. The influence on the development of cognitive functions and behaviour has also been displayed. This correlation justifies attempts to restore the beneficial the composition of the microbiome through the use of probiotics, vaginal microflora transfer in case of cesarean section and encouraging breastfeeding. Development of multiple studies on the topic of the human microbiome and its impact on the human body is necessary in order to reach final conclusions. The aim of this article is to summarize recent findings regarding the development of the human microbiome from the first days of life and the influence of changes in its composition on human health.}, }
@article {pmid31057522, year = {2019}, author = {Fiedorová, K and Radvanský, M and Němcová, E and Grombiříková, H and Bosák, J and Černochová, M and Lexa, M and Šmajs, D and Freiberger, T}, title = {The Impact of DNA Extraction Methods on Stool Bacterial and Fungal Microbiota Community Recovery.}, journal = {Frontiers in microbiology}, volume = {10}, number = {}, pages = {821}, doi = {10.3389/fmicb.2019.00821}, pmid = {31057522}, issn = {1664-302X}, abstract = {Our understanding of human gut microbiota in health and disease depends on accurate and reproducible microbial data acquisition. The critical step in this process is to apply an appropriate methodology to extract microbial DNA, since biases introduced during the DNA extraction process may result in inaccurate microbial representation. In this study, we attempted to find a DNA extraction protocol which could be effectively used to analyze both the bacterial and fungal community. We evaluated the effect of five DNA extraction methods (QIAamp DNA Stool Mini Kit, PureLinkTM Microbiome DNA Purification Kit, ZR Fecal DNA MiniPrepTM Kit, NucleoSpin® DNA Stool Kit, and IHMS protocol Q) on bacterial and fungal gut microbiome recovery using (i) a defined system of germ-free mice feces spiked with bacterial or fungal strains, and (ii) non-spiked human feces. In our experimental setup, we confirmed that the examined methods significantly differed in efficiency and quality, which affected the identified stool microbiome composition. In addition, our results indicated that fungal DNA extraction might be prone to be affected by reagent/kit contamination, and thus an appropriate blank control should be included in mycobiome research. Overall, standardized IHMS protocol Q, recommended by the International Human Microbiome Consortium, performed the best when considering all the parameters analyzed, and thus could be applied not only in bacterial, but also in fungal microbiome research.}, }
@article {pmid31055031, year = {2019}, author = {Seferovic, MD and Pace, RM and Carroll, M and Belfort, B and Major, AM and Chu, DM and Racusin, DA and Castro, ECC and Muldrew, KL and Versalovic, J and Aagaard, KM}, title = {Visualization of microbes by 16S in situ hybridization in term and preterm placentas without intraamniotic infection.}, journal = {American journal of obstetrics and gynecology}, volume = {221}, number = {2}, pages = {146.e1-146.e23}, doi = {10.1016/j.ajog.2019.04.036}, pmid = {31055031}, issn = {1097-6868}, abstract = {BACKGROUND: Numerous reports have documented bacteria in the placental membranes and basal plate decidua in the absence of immunopathology using histologic techniques. Similarly, independent metagenomic characterizations have identified an altered taxonomic makeup in association with spontaneous preterm birth. Here we sought to corroborate these findings by localizing presumptive intact bacteria using molecular histology within the placental microanatomy.<br><br>OBJECTIVE: Here we examined for microbes in term and preterm gestations using a signal-amplified 16S universal in situ hybridization probe set for bacterial rRNA, alongside traditional histologic methods of Warthin-Starry and Gram stains, as well as clinical culture methodologies. We further sought to differentiate accompanying 16S gene sequencing taxonomic profiles from germ-free (gnotobiotic) mouse and extraction and amplicon contamination controls.<br><br>STUDY DESIGN: Placentas were collected from a total of 53 subjects, composed of term labored (n = 4) and unlabored cesarean deliveries (n = 22) and preterm vaginal (n = 18) and cesarean deliveries (n = 8); a placenta from a single subject with clinical and histologic evident choriomanionitis was employed as a positive control (n = 1). The preterm cohort included spontaneous preterm birth with (n = 6) and without (n = 10) preterm premature rupture of membranes, as well as medically indicated preterm births (n = 10). Placental microbes were visualized using an in situ hybridization probe set designed against highly conserved regions of the bacterial 16S ribosome, which produces an amplified stable signal using branched DNA probes. Extracted bacterial nucleic acids from these same samples were subjected to 16S rRNA metagenomic sequencing (Illumina, V4) for course taxonomic analysis, alongside environmental and kit contaminant controls. A subset of unlabored, cesarean-delivered term pregnancies were also assessed with clinical culture for readily cultivatable pathogenic microbes.<br><br>RESULTS: Molecular in situ hybridization of bacterial rRNA enabled visualization and localization of low-abundance microbes after systematic high-power scanning. Despite the absence of clinical or histologic chorioamnionitis in 52 of 53 subjects, instances of 16S rRNA signal were confidently observed in 13 of 16 spontaneous preterm birth placentas, which was not significantly different from term unlabored cesarean specimens (18 of 22; P > .05). 16S rRNA signal was largely localized to the villous parenchyma and/or syncytiotrophoblast, and less commonly the chorion and the maternal intervillous space. In all term and unlabored cesarean deliveries, visualization of evident placental microbes by in situ hybridization occurred in the absence of clinical or histologic detection using conventional clinical cultivation, hematoxylin-eosin, and Gram staining. In 1 subject, appreciable villous bacteria localized to an infarction, where 16S microbial detection was confirmed by Warthin-Starry stain. In all instances, parallel sample principle coordinate analysis using Bray-Cutis distances of 16S rRNA gene sequencing data demonstrated consistent taxonomic distinction from all negative or potential contamination controls (P = .024, PERMANOVA). Classification from contaminant filtered data identified a distinct taxonomic makeup among term and preterm cohorts when compared with contaminant controls (false discovery rate <0.05).<br><br>CONCLUSION: Presumptively intact placental microbes are visualized as low-abundance, low-biomass and sparse populations within the placenta regardless of gestational age and mode of delivery. Their taxonomic makeup is distinct from contamination controls. These findings further support several previously published findings, including our own, which have used metagenomics to characterize low-abundance and low-biomass microbial communities in the placenta.}, }
@article {pmid31047664, year = {2019}, author = {Chetwynd, AJ and Ogilvie, LA and Nzakizwanayo, J and Pazdirek, F and Hoch, J and Dedi, C and Gilbert, D and Abdul-Sada, A and Jones, BV and Hill, EM}, title = {The potential of nanoflow liquid chromatography-nano electrospray ionisation-mass spectrometry for global profiling the faecal metabolome.}, journal = {Journal of chromatography. A}, volume = {1600}, number = {}, pages = {127-136}, doi = {10.1016/j.chroma.2019.04.028}, pmid = {31047664}, issn = {1873-3778}, mesh = {Bile Acids and Salts/analysis ; *Chromatography, Liquid ; Eicosanoids/analysis ; Feces/*chemistry ; Female ; Healthy Volunteers ; Humans ; Male ; *Metabolome ; Metabolomics ; Phospholipids/analysis ; Pilot Projects ; *Spectrometry, Mass, Electrospray Ionization ; }, abstract = {Faeces are comprised of a wide array of metabolites arising from the circulatory system as well as the human microbiome. A global metabolite analysis (metabolomics) of faecal extracts offers the potential to uncover new compounds which may be indicative of the onset of bowel diseases such as colorectal cancer (CRC). To date, faecal metabolomics is still in its infancy and the compounds of low abundance present in faecal extracts poorly characterised. In this study, extracts of faeces from healthy subjects were profiled using a sensitive nanoflow-nanospray LC-MS platform which resulted in highly repeatable peak retention times (<2% CV) and intensities (<15% CV). Analysis of the extracts revealed wide coverage of the faecal metabolome including detection of low abundant signalling compounds such as sex steroids and eicosanoids, alongside highly abundant pharmaceuticals and tetrapyrrole metabolites. A small pilot study investigating differences in metabolomics profiles of faecal samples obtained from 7 CRC, 25 adenomatous polyp and 26 healthy groups revealed that secondary bile acids, conjugated androgens, eicosanoids, phospholipids and an unidentified haem metabolite were potential classes of metabolites that discriminated between the CRC and control sample groups. However, much larger follow up studies are needed to confirm which components of the faecal metabolome are associated with actual CRC disease rather than dietary influences. This study reveals the potential of nanospray-nanoflow LC-MS profiling of faecal samples from large scale cohort studies for uncovering the role of the faecal metabolome in colorectal disease formation.}, }
@article {pmid31046835, year = {2019}, author = {Sharma, A and Richardson, M and Cralle, L and Stamper, CE and Maestre, JP and Stearns-Yoder, KA and Postolache, TT and Bates, KL and Kinney, KA and Brenner, LA and Lowry, CA and Gilbert, JA and Hoisington, AJ}, title = {Longitudinal homogenization of the microbiome between both occupants and the built environment in a cohort of United States Air Force Cadets.}, journal = {Microbiome}, volume = {7}, number = {1}, pages = {70}, doi = {10.1186/s40168-019-0686-6}, pmid = {31046835}, issn = {2049-2618}, support = {G-2016-7077//Alfred P. Sloan Foundation/ ; }, abstract = {BACKGROUND: The microbiome of the built environment has important implications for human health and wellbeing; however, bidirectional exchange of microbes between occupants and surfaces can be confounded by lifestyle, architecture, and external environmental exposures. Here, we present a longitudinal study of United States Air Force Academy cadets (n = 34), which have substantial homogeneity in lifestyle, diet, and age, all factors that influence the human microbiome. We characterized bacterial communities associated with (1) skin and gut samples from roommate pairs, (2) four built environment sample locations inside the pairs' dormitory rooms, (3) four built environment sample locations within shared spaces in the dormitory, and (4) room-matched outdoor samples from the window ledge of their rooms.<br><br>RESULTS: We analyzed 2,170 samples, which generated 21,866 unique amplicon sequence variants. Linear convergence of microbial composition and structure was observed between an occupants' skin and the dormitory surfaces that were only used by that occupant (i.e., desk). Conversely, bacterial community beta diversity (weighted Unifrac) convergence between the skin of both roommates and the shared dormitory floor between the two cadet's beds was not seen across the entire study population. The sampling period included two semester breaks in which the occupants vacated their rooms; upon their return, the beta diversity similarity between their skin and the surfaces had significantly decreased compared to before the break (p < 0.05). There was no apparent convergence between the gut and building microbiota, with the exception of communal bathroom door-handles, which suggests that neither co-occupancy, diet, or lifestyle homogenization had a significant impact on gut microbiome similarity between these cadets over the observed time frame. As a result, predictive classifier models were able to identify an individual more accurately based on the gut microbiota (74%) compared to skin (51%).<br><br>CONCLUSIONS: To the best of our knowledge, this is the first study to show an increase in skin microbial similarity of two individuals who start living together for the first time and who are not genetically related or romantically involved. Cohabitation was significantly associated with increased skin microbiota similarity but did not significantly influence the gut microbiota. Following a departure from the occupied space of several weeks, the skin microbiota, but not the gut microbiota, showed a significant reduction in similarity relative to the building. Overall, longitudinal observation of these dynamics enables us to dissect the influence of occupation, diet, and lifestyle factors on occupant and built environment microbial ecology.}, }
@article {pmid31042284, year = {2019}, author = {Vangay, P and Hillmann, BM and Knights, D}, title = {Microbiome Learning Repo (ML Repo): A public repository of microbiome regression and classification tasks.}, journal = {GigaScience}, volume = {8}, number = {5}, pages = {}, doi = {10.1093/gigascience/giz042}, pmid = {31042284}, issn = {2047-217X}, support = {R01 AI121383/NIAID NIH HHS/National Institute of Allergy and Infectious Diseases Extramural Activities/United States ; }, abstract = {The use of machine learning in high-dimensional biological applications, such as the human microbiome, has grown exponentially in recent years, but algorithm developers often lack the domain expertise required for interpretation and curation of the heterogeneous microbiome datasets. We present Microbiome Learning Repo (ML Repo, available at https://knights-lab.github.io/MLRepo/), a public, web-based repository of 33 curated classification and regression tasks from 15 published human microbiome datasets. We highlight the use of ML Repo in several use cases to demonstrate its wide application, and we expect it to be an important resource for algorithm developers.}, }
@article {pmid31028005, year = {2019}, author = {Zhao, S and Lieberman, TD and Poyet, M and Kauffman, KM and Gibbons, SM and Groussin, M and Xavier, RJ and Alm, EJ}, title = {Adaptive Evolution within Gut Microbiomes of Healthy People.}, journal = {Cell host &amp; microbe}, volume = {25}, number = {5}, pages = {656-667.e8}, doi = {10.1016/j.chom.2019.03.007}, pmid = {31028005}, issn = {1934-6069}, abstract = {Natural selection shapes bacterial evolution in all environments. However, the extent to which commensal bacteria diversify and adapt within the human gut remains unclear. Here, we combine culture-based population genomics and metagenomics to investigate the within-microbiome evolution of Bacteroides fragilis. We find that intra-individual B. fragilis populations contain substantial de novo nucleotide and mobile element diversity, preserving years of within-person history. This history reveals multiple signatures of within-person adaptation, including parallel evolution in sixteen genes. Many of these genes are implicated in cell-envelope biosynthesis and polysaccharide utilization. Tracking evolutionary trajectories using near-daily metagenomic sampling, we find evidence for years-long coexistence in one subject despite adaptive dynamics. We used public metagenomes to investigate one adaptive mutation common in our cohort and found that it emerges frequently in Western, but not Chinese, microbiomes. Collectively, these results demonstrate that B. fragilis adapts within individual microbiomes, pointing to factors that promote long-term gut colonization.}, }
@article {pmid31024514, year = {2019}, author = {Raju, SC and Lagström, S and Ellonen, P and de Vos, WM and Eriksson, JG and Weiderpass, E and Rounge, TB}, title = {Gender-Specific Associations Between Saliva Microbiota and Body Size.}, journal = {Frontiers in microbiology}, volume = {10}, number = {}, pages = {767}, doi = {10.3389/fmicb.2019.00767}, pmid = {31024514}, issn = {1664-302X}, abstract = {Objective: The human intestinal microbiota likely play an important role in the development of overweight and obesity. However, the associations between saliva microbiota and body mass index (BMI) have been sparsely studied. The aim of this study was to identify the associations between saliva microbiota and body size in Finnish children.<br><br>Methods: The saliva microbiota of 900 Finnish children, aged 11-14 years with measured height and weight, was characterized using 16S rRNA (V3-V4) sequencing.<br><br>Results: The core saliva microbiota consisted of 14 genera that were present in more than 95% of the Finnish children. The saliva microbiota profiles were gender-specific with higher alpha-diversity in boys than girls and significant differences between the genders in community composition and abundances. Alpha-diversity differed between normal weight and overweight girls and between normal weight and obese boys. The composition was dissimilar between normal weight and obese girls, but not in boys. The relative abundance profiles differed according to body size. Decrease in commensal saliva bacteria were observed in all the body sizes when compared to normal weight children. Notably, the relative abundance of bacteria related to, Veillonella, Prevotella, Selenomonas, and Streptococcus was reduced in obese children.<br><br>Conclusion: Saliva microbiota diversity and composition were significantly associated with body size and gender in Finnish children. Body size-specific saliva microbiota profiles open new avenues for studying the potential roles of microbiota in weight development and management.}, }
@article {pmid31021803, year = {2019}, author = {Wassan, JT and Wang, H and Browne, F and Zheng, H}, title = {Phy-PMRFI: Phylogeny-Aware Prediction of Metagenomic Functions Using Random Forest Feature Importance.}, journal = {IEEE transactions on nanobioscience}, volume = {18}, number = {3}, pages = {273-282}, doi = {10.1109/TNB.2019.2912824}, pmid = {31021803}, issn = {1558-2639}, abstract = {High-throughput sequencing techniques have accelerated functional metagenomics studies through the generation of large volumes of omics data. The integration of these data using computational approaches is potentially useful for predicting metagenomic functions. Machine learning (ML) models can be trained using microbial features which are then used to classify microbial data into different functional classes. For example, ML analyses over the human microbiome data has been linked to the prediction of important biological states. For analysing omics data, integrating abundance count of taxonomical features with their biological relationships is important. These relationships can potentially be uncovered from the phylogenetic tree of microbial taxa. In this paper, we propose a novel integrative framework Phy-PMRFI. This framework is driven by the phylogeny-based modeling of omics data to predict metagenomic functions using important features selected by a random forest importance (RFI) strategy. The proposed framework integrates the underlying phylogenetic tree information with abundance measures of microbial species (features) by creating a novel phylogeny and abundance aware matrix structure (PAAM). Phy-PMRFI progresses by ranking the microbial features using an RFI measure. This is then used as input for microbiome classification. The resultant feature set enhances the performance of the state-of-art methods such as support vector machines. Our proposed integrative framework also outperforms the state-of-the-art pipeline of phylogenetic isometric log-ratio transform (PhILR) and MetaPhyl. Prediction accuracy of 90 % is obtained with Phy-PMRFI over human throat microbiome in comparison to other approaches of PhILR with 53% and MetaPhyl with 71% accuracy.}, }
@article {pmid31009573, year = {2019}, author = {Zhang, X and Figeys, D}, title = {Perspective and Guidelines for Metaproteomics in Microbiome Studies.}, journal = {Journal of proteome research}, volume = {18}, number = {6}, pages = {2370-2380}, doi = {10.1021/acs.jproteome.9b00054}, pmid = {31009573}, issn = {1535-3907}, abstract = {The microbiome is emerging as a prominent factor affecting human health, and its dysbiosis is associated with various diseases. Compositional profiling of microbiome is increasingly being supplemented with functional characterization. Metaproteomics is intrinsically focused on functional changes and therefore will be an important tool in those studies of the human microbiome. In the past decade, development of new experimental and bioinformatic approaches for metaproteomics has enabled large-scale human metaproteomic studies. However, challenges still exist, and there remains a lack of standardizations and guidelines for properly performing metaproteomic studies on human microbiome. Herein, we provide a perspective of recent developments, the challenges faced, and the future directions of metaproteomics and its applications. In addition, we propose a set of guidelines/recommendations for performing and reporting the results from metaproteomic experiments for the study of human microbiomes. We anticipate that these guidelines will be optimized further as more metaproteomic questions are raised and addressed, and metaproteomic applications are published, so that they are eventually recognized and applied in the field.}, }
@article {pmid31009405, year = {2019}, author = {Holster, S and Lindqvist, CM and Repsilber, D and Salonen, A and de Vos, WM and König, J and Brummer, RJ}, title = {The Effect of Allogenic Versus Autologous Fecal Microbiota Transfer on Symptoms, Visceral Perception and Fecal and Mucosal Microbiota in Irritable Bowel Syndrome: A Randomized Controlled Study.}, journal = {Clinical and translational gastroenterology}, volume = {10}, number = {4}, pages = {e00034}, doi = {10.14309/ctg.0000000000000034}, pmid = {31009405}, issn = {2155-384X}, abstract = {OBJECTIVES: Fecal microbiota transfer (FMT) is suggested as a potential treatment for patients with irritable bowel syndrome (IBS). We aimed to study the effect of allogenic and autologous FMT on IBS symptoms, visceral sensitivity, and compositional changes in fecal and mucosa-adherent microbiota.<br><br>METHODS: Seventeen patients with IBS were randomized either to receive fecal material from a healthy donor (allogenic) or to receive their own fecal material (autologous). The fecal material was administered into the cecum by whole colonoscopy after bowel cleansing.<br><br>RESULTS: No significant differences were found between the allogenic and the autologous FMT regarding symptom scores. However, symptom scores of patients receiving allogenic fecal material significantly decreased after FMT compared with baseline (P = 0.02), which was not the case in the autologous group (P = 0.16). Visceral sensitivity was not affected except for a small beneficial effect on urge scores in the autologous group (P < 0.05). While both fecal and mucosa-adherent microbiota of some patients shifted to their respective donor's fecal microbiota, some patients showed no relevant microbial changes after allogenic FMT. Large compositional shifts in fecal and mucosa-adherent microbiota also occurred in the autologous group.<br><br>CONCLUSIONS: This study showed that a single FMT by colonoscopy may have beneficial effects in IBS; however, the allogenic fecal material was not superior to the autologous fecal material. This suggests that bowel cleansing prior to the colonoscopy and/or processing of the fecal material as part of the FMT routine contribute to symptoms and gut microbiota composition changes in IBS.}, }
@article {pmid31005411, year = {2019}, author = {Hollister, EB and Oezguen, N and Chumpitazi, BP and Luna, RA and Weidler, EM and Rubio-Gonzales, M and Dahdouli, M and Cope, JL and Mistretta, TA and Raza, S and Metcalf, GA and Muzny, DM and Gibbs, RA and Petrosino, JF and Heitkemper, M and Savidge, TC and Shulman, RJ and Versalovic, J}, title = {Leveraging Human Microbiome Features to Diagnose and Stratify Children with Irritable Bowel Syndrome.}, journal = {The Journal of molecular diagnostics : JMD}, volume = {21}, number = {3}, pages = {449-461}, doi = {10.1016/j.jmoldx.2019.01.006}, pmid = {31005411}, issn = {1943-7811}, support = {U01 AI124290/AI/NIAID NIH HHS/United States ; K23 DK101688/DK/NIDDK NIH HHS/United States ; R01 NR013497/NR/NINR NIH HHS/United States ; R03 DK117219/DK/NIDDK NIH HHS/United States ; R01 NR005337/NR/NINR NIH HHS/United States ; }, abstract = {Accurate diagnosis and stratification of children with irritable bowel syndrome (IBS) remain challenging. Given the central role of recurrent abdominal pain in IBS, we evaluated the relationships of pediatric IBS and abdominal pain with intestinal microbes and fecal metabolites using a comprehensive clinical characterization and multiomics strategy. Using rigorous clinical phenotyping, we identified preadolescent children (aged 7 to 12 years) with Rome III IBS (n = 23) and healthy controls (n = 22) and characterized their fecal microbial communities using whole-genome shotgun metagenomics and global unbiased fecal metabolomic profiling. Correlation-based approaches and machine learning algorithms identified associations between microbes, metabolites, and abdominal pain. IBS cases differed from controls with respect to key bacterial taxa (eg, Flavonifractor plautii and Lachnospiraceae bacterium 7_1_58FAA), metagenomic functions (eg, carbohydrate metabolism and amino acid metabolism), and higher-order metabolites (eg, secondary bile acids, sterols, and steroid-like compounds). Significant associations between abdominal pain frequency and severity and intestinal microbial features were identified. A random forest classifier built on metagenomic and metabolic markers successfully distinguished IBS cases from controls (area under the curve, 0.93). Leveraging multiple lines of evidence, intestinal microbes, genes/pathways, and metabolites were associated with IBS, and these features were capable of distinguishing children with IBS from healthy children. These multi-omics features, and their links to childhood IBS coupled with nutritional interventions, may lead to new microbiome-guided diagnostic and therapeutic strategies.}, }
@article {pmid31003081, year = {2019}, author = {Díez López, C and Vidaki, A and Ralf, A and Montiel González, D and Radjabzadeh, D and Kraaij, R and Uitterlinden, AG and Haas, C and Lao, O and Kayser, M}, title = {Novel taxonomy-independent deep learning microbiome approach allows for accurate classification of different forensically relevant human epithelial materials.}, journal = {Forensic science international. Genetics}, volume = {41}, number = {}, pages = {72-82}, doi = {10.1016/j.fsigen.2019.03.015}, pmid = {31003081}, issn = {1878-0326}, mesh = {*Deep Learning ; Female ; Forensic Genetics/methods ; *High-Throughput Nucleotide Sequencing ; Humans ; Male ; *Microbiota ; RNA, Ribosomal, 16S/*genetics ; Saliva/microbiology ; *Sequence Analysis, RNA ; Skin/microbiology ; Vagina/microbiology ; }, abstract = {Correct identification of different human epithelial materials such as from skin, saliva and vaginal origin is relevant in forensic casework as it provides crucial information for crime reconstruction. However, the overlap in human cell type composition between these three epithelial materials provides challenges for their differentiation and identification when using previously proposed human cell biomarkers, while their microbiota composition largely differs. By using validated 16S rRNA gene massively parallel sequencing data from the Human Microbiome Project of 1636 skin, oral and vaginal samples, 50 taxonomy-independent deep learning networks were trained to classify these three tissues. Validation testing was performed in de-novo generated high-throughput 16S rRNA gene sequencing data using the Ion Torrent™ Personal Genome Machine from 110 test samples: 56 hand skin, 31 saliva and 23 vaginal secretion specimens. Body-site classification accuracy of these test samples was very high as indicated by AUC values of 0.99 for skin, 0.99 for oral, and 1 for vaginal secretion. Misclassifications were limited to 3 (5%) skin samples. Additional forensic validation testing was performed in mock casework samples by de-novo high-throughput sequencing of 19 freshly-prepared samples and 22 samples aged for 1 up to 7.6 years. All of the 19 fresh and 20 (91%) of the 22 aged mock casework samples were correctly tissue-type classified. Moreover, comparing the microbiome results with outcomes from previous human mRNA-based tissue identification testing in the same 16 aged mock casework samples reveals that our microbiome approach performs better in 12 (75%), similarly in 2 (12.5%), and less good in 2 (12.5%) of the samples. Our results demonstrate that this new microbiome approach allows for accurate tissue-type classification of three human epithelial materials of skin, oral and vaginal origin, which is highly relevant for future forensic investigations.}, }
@article {pmid30994455, year = {2019}, author = {Inkpen, SA}, title = {Health, ecology and the microbiome.}, journal = {eLife}, volume = {8}, number = {}, pages = {}, doi = {10.7554/eLife.47626}, pmid = {30994455}, issn = {2050-084X}, abstract = {Advances in microbiomics have changed the way in which many researchers think about health and disease. These changes have also raised a number of philosophical questions around these topics, such as the types of living systems to which these concepts can be applied. Here, I discuss the human microbiome from two perspectives: the first treats the microbiome as part of a larger system that includes the human; the second treats the microbiome as an independent ecosystem that provides services to humans. Drawing on the philosophy of medicine and ecology, I explore two questions: i) how can we make sense of disease and dysfunction in these two perspectives? ii) are these two perspectives complimentary or do they compete with each other?}, }
@article {pmid30994187, year = {2019}, author = {Wang, T and Yang, C and Zhao, H}, title = {Prediction analysis for microbiome sequencing data.}, journal = {Biometrics}, volume = {}, number = {}, pages = {}, doi = {10.1111/biom.13061}, pmid = {30994187}, issn = {1541-0420}, support = {11601326//National Natural Science Foundation of China/ ; 2018YFC0910500//National Key R&amp;D Program of China/ ; 2017SHZDZX01//Shanghai Municipal Science and Technology Major Project/ ; //Neil Shen's SJTU Medical Research Fund/ ; 12316116//Hong Kong Research Grant Council/ ; 22302815//Hong Kong Research Grant Council/ ; 12301417//Hong Kong Research Grant Council/ ; 16307818//Hong Kong Research Grant Council/ ; IGN17SC02//Initiation Grant from University Grants Committee/ ; R9405//Hong Kong University of Science and Technology/ ; }, abstract = {One goal of human microbiome studies is to relate host traits with human microbiome compositions. The analysis of microbial community sequencing data presents great statistical challenges, especially when the samples have different library sizes and the data are overdispersed with many zeros. To address these challenges, we introduce a new statistical framework, called predictive analysis in metagenomics via inverse regression (PAMIR), to analyze microbiome sequencing data. Within this framework, an inverse regression model is developed for overdispersed microbiota counts given the trait, and then a prediction rule is constructed by taking advantage of the dimension-reduction structure in the model. An efficient Monte Carlo expectation-maximization algorithm is proposed for maximum likelihood estimation. The method is further generalized to accommodate other types of covariates. We demonstrate the advantages of PAMIR through simulations and two real data examples.}, }
@article {pmid30993039, year = {2019}, author = {Garretto, A and Hatzopoulos, T and Putonti, C}, title = {virMine: automated detection of viral sequences from complex metagenomic samples.}, journal = {PeerJ}, volume = {7}, number = {}, pages = {e6695}, doi = {10.7717/peerj.6695}, pmid = {30993039}, issn = {2167-8359}, abstract = {Metagenomics has enabled sequencing of viral communities from a myriad of different environments. Viral metagenomic studies routinely uncover sequences with no recognizable homology to known coding regions or genomes. Nevertheless, complete viral genomes have been constructed directly from complex community metagenomes, often through tedious manual curation. To address this, we developed the software tool virMine to identify viral genomes from raw reads representative of viral or mixed (viral and bacterial) communities. virMine automates sequence read quality control, assembly, and annotation. Researchers can easily refine their search for a specific study system and/or feature(s) of interest. In contrast to other viral genome detection tools that often rely on the recognition of viral signature sequences, virMine is not restricted by the insufficient representation of viral diversity in public data repositories. Rather, viral genomes are identified through an iterative approach, first omitting non-viral sequences. Thus, both relatives of previously characterized viruses and novel species can be detected, including both eukaryotic viruses and bacteriophages. Here we present virMine and its analysis of synthetic communities as well as metagenomic data sets from three distinctly different environments: the gut microbiota, the urinary microbiota, and freshwater viromes. Several new viral genomes were identified and annotated, thus contributing to our understanding of viral genetic diversity in these three environments.}, }
@article {pmid30992349, year = {2019}, author = {Aleti, G and Baker, JL and Tang, X and Alvarez, R and Dinis, M and Tran, NC and Melnik, AV and Zhong, C and Ernst, M and Dorrestein, PC and Edlund, A}, title = {Identification of the Bacterial Biosynthetic Gene Clusters of the Oral Microbiome Illuminates the Unexplored Social Language of Bacteria during Health and Disease.}, journal = {mBio}, volume = {10}, number = {2}, pages = {}, doi = {10.1128/mBio.00321-19}, pmid = {30992349}, issn = {2150-7511}, support = {F32 DE026947/DE/NIDCR NIH HHS/United States ; K99 DE024543/DE/NIDCR NIH HHS/United States ; R00 DE024543/DE/NIDCR NIH HHS/United States ; }, mesh = {Bacteria/genetics/isolation &amp; purification ; Biosynthetic Pathways/*genetics ; Child ; Child, Preschool ; Computational Biology ; Dental Caries/microbiology ; Dysbiosis ; Humans ; Mass Spectrometry ; Metagenome ; *Microbial Interactions ; Microbiota/*genetics ; Mouth/*microbiology ; *Multigene Family ; Periodontitis/microbiology ; Saliva/microbiology ; }, abstract = {Small molecules are the primary communication media of the microbial world. Recent bioinformatic studies, exploring the biosynthetic gene clusters (BGCs) which produce many small molecules, have highlighted the incredible biochemical potential of the signaling molecules encoded by the human microbiome. Thus far, most research efforts have focused on understanding the social language of the gut microbiome, leaving crucial signaling molecules produced by oral bacteria and their connection to health versus disease in need of investigation. In this study, a total of 4,915 BGCs were identified across 461 genomes representing a broad taxonomic diversity of oral bacteria. Sequence similarity networking provided a putative product class for more than 100 unclassified novel BGCs. The newly identified BGCs were cross-referenced against 254 metagenomes and metatranscriptomes derived from individuals either with good oral health or with dental caries or periodontitis. This analysis revealed 2,473 BGCs, which were differentially represented across the oral microbiomes associated with health versus disease. Coabundance network analysis identified numerous inverse correlations between BGCs and specific oral taxa. These correlations were present in healthy individuals but greatly reduced in individuals with dental caries, which may suggest a defect in colonization resistance. Finally, corroborating mass spectrometry identified several compounds with homology to products of the predicted BGC classes. Together, these findings greatly expand the number of known biosynthetic pathways present in the oral microbiome and provide an atlas for experimental characterization of these abundant, yet poorly understood, molecules and socio-chemical relationships, which impact the development of caries and periodontitis, two of the world's most common chronic diseases.IMPORTANCE The healthy oral microbiome is symbiotic with the human host, importantly providing colonization resistance against potential pathogens. Dental caries and periodontitis are two of the world's most common and costly chronic infectious diseases and are caused by a localized dysbiosis of the oral microbiome. Bacterially produced small molecules, often encoded by BGCs, are the primary communication media of bacterial communities and play a crucial, yet largely unknown, role in the transition from health to dysbiosis. This study provides a comprehensive mapping of the BGC repertoire of the human oral microbiome and identifies major differences in health compared to disease. Furthermore, BGC representation and expression is linked to the abundance of particular oral bacterial taxa in health versus dental caries and periodontitis. Overall, this study provides a significant insight into the chemical communication network of the healthy oral microbiome and how it devolves in the case of two prominent diseases.}, }
@article {pmid30981803, year = {2019}, author = {Parida, S and Sharma, D}, title = {The power of small changes: Comprehensive analyses of microbial dysbiosis in breast cancer.}, journal = {Biochimica et biophysica acta. Reviews on cancer}, volume = {1871}, number = {2}, pages = {392-405}, doi = {10.1016/j.bbcan.2019.04.001}, pmid = {30981803}, issn = {1879-2561}, support = {R01 CA204555/NCI NIH HHS/National Cancer Institute/United States ; }, mesh = {Animals ; Breast Neoplasms/*microbiology ; *Dysbiosis ; Female ; Humans ; }, abstract = {Disparate occurrence of breast cancer remains an intriguing question since only a subset of women with known risk factors develop cancer. Recent studies suggest an active role of local and distant microbiota in breast cancer initiation, progression, and overall prognosis. A dysbiotic microbiota predisposes the body to develop cancer by inducing genetic instability, initiating DNA damage and proliferation of the damaged progeny, eliciting favorable immune response, metabolic dysregulation and altered response to therapy. In this review, we present our analyses of the existing datasets and discuss the local dysbiosis observed in breast cancer patients and different aspects of breast carcinogenesis that can be potentially influenced by local breast microbiota. Striking differences between microbial community compositions in breast of cancer patients compared to healthy individuals were noted. Differences in microbiome were also apparent between benign and malignant disease and between nipple aspirate fluid of healthy individuals and breast survivors. We also discuss the identification of distinct bacterial, fungal, viral as well as parasite signatures for breast cancer. These microbes are capable of producing numerous secondary metabolites that can act as signaling mediators effecting breast cancer progression. We review how microbes potentially alter response to therapy affecting drug metabolism, pharmacokinetics, anti-tumor effects and toxicity. In conclusion, breast harbors a community of microbes that can communicate with the host cells inducing downstream signaling pathways and modulating various aspects of breast cancer growth and metastatic progression and an improved understanding of microbial dysbiosis can potentially reduce breast cancer risk and improve outcomes of breast cancer patients. The human microbiome, now referred to as, the &quot;forgotten organ&quot; contains a metagenome that is 100-fold more diverse compared to the human genome, thereby, is critically associated with human health [1,2]. With the revelations of the human microbiome project and advent of deep sequencing techniques, a plethora of information has been acquired in recent years. Body sites like stomach, bladder and lungs, once thought to be sterile, are now known to harbor millions of indigenous microbial species. Approximately 80% of the healthy microbiome consists of Firmicutes and Bacteroidetes accompanied by Verrucomicrobia, Actinobacteria, Proteobacteria, Tenericutes and Cyanobacteria [2-7]. The role of microbiome in diabetes, obesity and even neurodegenerative diseases was greatly appreciated in the last decade [1,7-14] and now it has been established that microbiome significantly contributes to many organ specific cancers [1,15,16].}, }
@article {pmid30979072, year = {2019}, author = {Lerner, A and Shoenfeld, Y and Matthias, T}, title = {Probiotics: If It Does Not Help It Does Not Do Any Harm. Really?.}, journal = {Microorganisms}, volume = {7}, number = {4}, pages = {}, doi = {10.3390/microorganisms7040104}, pmid = {30979072}, issn = {2076-2607}, abstract = {Probiotics per definition should have beneficial effects on human health, and their consumption has tremendously increased in the last decades. In parallel, the amount of published material and claims for their beneficial efficacy soared continuously. Recently, multiple systemic reviews, meta-analyses, and expert opinions expressed criticism on their claimed effects and safety. The present review describes the dark side of the probiotics, in terms of problematic research design, incomplete reporting, lack of transparency, and under-reported safety. Highlighted are the potential virulent factors and the mode of action in the intestinal lumen, risking the physiological microbiome equilibrium. Finally, regulatory topics are discussed to lighten the heterogeneous guidelines applied worldwide. The shift in the scientific world towards a better understanding of the human microbiome, before consumption of the probiotic cargo, is highly endorsed. It is hoped that better knowledge will extend the probiotic repertoire, re-confirm efficacy or safety, establish their efficacy and substantiate their beneficial effects.}, }
@article {pmid30976019, year = {2019}, author = {Jeong, H and Arif, B and Caetano-Anollés, G and Kim, KM and Nasir, A}, title = {Horizontal gene transfer in human-associated microorganisms inferred by phylogenetic reconstruction and reconciliation.}, journal = {Scientific reports}, volume = {9}, number = {1}, pages = {5953}, doi = {10.1038/s41598-019-42227-5}, pmid = {30976019}, issn = {2045-2322}, support = {20140428//Ministry of Oceans and Fisheries (MOF)/ ; 21 519/SRGP/R&amp;D/HEC/2014//Higher Education Commission, Pakistan (HEC)/ ; }, abstract = {Horizontal gene transfer (HGT) is widespread in the evolution of prokaryotes, especially those associated with the human body. Here, we implemented large-scale gene-species phylogenetic tree reconstructions and reconciliations to identify putative HGT-derived genes in the reference genomes of microbiota isolated from six major human body sites by the NIH Human Microbiome Project. Comparisons with a control group representing microbial genomes from diverse natural environments indicated that HGT activity increased significantly in the genomes of human microbiota, which is confirmatory of previous findings. Roughly, more than half of total genes in the genomes of human-associated microbiota were transferred (donated or received) by HGT. Up to 60% of the detected HGTs occurred either prior to the colonization of the human body or involved bacteria residing in different body sites. The latter could suggest 'genetic crosstalk' and movement of bacterial genes within the human body via hitherto poorly understood mechanisms. We also observed that HGT activity increased significantly among closely-related microorganisms and especially when they were united by physical proximity, suggesting that the 'phylogenetic effect' can significantly boost HGT activity. Finally, we identified several core and widespread genes least influenced by HGT that could become useful markers for building robust 'trees of life' and address several outstanding technical challenges to improve the phylogeny-based genome-wide HGT detection method for future applications.}, }
@article {pmid30959425, year = {2019}, author = {Shetty, SA and Smidt, H and de Vos, WM}, title = {Reconstructing functional networks in the human intestinal tract using synthetic microbiomes.}, journal = {Current opinion in biotechnology}, volume = {58}, number = {}, pages = {146-154}, doi = {10.1016/j.copbio.2019.03.009}, pmid = {30959425}, issn = {1879-0429}, abstract = {The human intestinal tract harbors one of the most densely populated and open microbial ecosystems. The application of multi-omics approaches has provided insight into a wide array of complex interactions between the various groups of mainly anaerobic colonic microbes as well as the host-microbe dialogue. Integration of multi-omics techniques in cultivation based experiments that vary in complexity from monocultures to synthetic microbial communities identified key metabolic players in the trophic interactions as well as their ecological dynamics. A synergy between these approaches will be of utmost importance to reconstruct the functional interaction networks at the ecosystem level within the human intestinal microbiome. The improved understanding of microbiome functioning at ecosystem level will further aid in developing better predictive models and design of effective microbiome modulation strategies for health benefits.}, }
@article {pmid30958298, year = {2019}, author = {Algazina, T and Yermekbayeva, B and Batpenova, G and Kushugulova, A}, title = {FEATURES OF MICROBIOTA IN PSORIATIC DISEASE: FROM SKIN AND GUT PERSPECTIVES (REVIEW).}, journal = {Georgian medical news}, volume = {}, number = {287}, pages = {98-104}, pmid = {30958298}, issn = {1512-0112}, mesh = {Arthritis, Psoriatic/*microbiology/pathology ; Dermatitis, Atopic ; Humans ; *Microbiota ; Psoriasis/*microbiology/pathology ; Skin/*microbiology/pathology ; }, abstract = {Psoriatic disease is a chronic inflammatory disease characterized by skin lesions. Psoriasis development has been associated both with genetic and environmental factors. Though skin and gut microbiota has been implicated in number of pathologies including atopic dermatitis, inflammatory bowel disease, Crohn's disease, allergy, and obesity, its role has been poorly studied in psoriatic disease, which incorporates both psoriasis and psoriatic arthritis. This literature review summarizes the most recent and major findings on microbiota features in psoriatic disease. Despite conflicting findings, psoriasis patients were frequently found to have distinct microbial composition in both skin and guts especially in the major bacterial phyla, Firmicutes, Bacteroidetes, and genus Akkermansia. Furthermore, bacterial DNA has been found in psoriatic patients both locally and systemically, and altogether suggesting a crucial role of bacteria in psoriatic disease and future studies in this field.}, }
@article {pmid30955503, year = {2019}, author = {Checinska Sielaff, A and Urbaniak, C and Mohan, GBM and Stepanov, VG and Tran, Q and Wood, JM and Minich, J and McDonald, D and Mayer, T and Knight, R and Karouia, F and Fox, GE and Venkateswaran, K}, title = {Characterization of the total and viable bacterial and fungal communities associated with the International Space Station surfaces.}, journal = {Microbiome}, volume = {7}, number = {1}, pages = {50}, doi = {10.1186/s40168-019-0666-x}, pmid = {30955503}, issn = {2049-2618}, mesh = {Bacteria/*classification/genetics/isolation &amp; purification ; Confined Spaces ; Environmental Microbiology ; Fungi/*classification/genetics/isolation &amp; purification ; Humans ; Microbiological Techniques/*methods ; Phylogeny ; Sequence Analysis, DNA/*methods ; Spacecraft ; Weightlessness ; }, abstract = {BACKGROUND: The International Space Station (ISS) is a closed system inhabited by microorganisms originating from life support systems, cargo, and crew that are exposed to unique selective pressures such as microgravity. To date, mandatory microbial monitoring and observational studies of spacecraft and space stations have been conducted by traditional culture methods, although it is known that many microbes cannot be cultured with standard techniques. To fully appreciate the true number and diversity of microbes that survive in the ISS, molecular and culture-based methods were used to assess microbial communities on ISS surfaces. Samples were taken at eight pre-defined locations during three flight missions spanning 14 months and analyzed upon return to Earth.<br><br>RESULTS: The cultivable bacterial and fungal population ranged from 104 to 109 CFU/m2 depending on location and consisted of various bacterial (Actinobacteria, Firmicutes, and Proteobacteria) and fungal (Ascomycota and Basidiomycota) phyla. Amplicon sequencing detected more bacterial phyla when compared to the culture-based analyses, but both methods identified similar numbers of fungal phyla. Changes in bacterial and fungal load (by culture and qPCR) were observed over time but not across locations. Bacterial community composition changed over time, but not across locations, while fungal community remained the same between samplings and locations. There were no significant differences in community composition and richness after propidium monoazide sample treatment, suggesting that the analyzed DNA was extracted from intact/viable organisms. Moreover, approximately 46% of intact/viable bacteria and 40% of intact/viable fungi could be cultured.<br><br>CONCLUSIONS: The results reveal a diverse population of bacteria and fungi on ISS environmental surfaces that changed over time but remained similar between locations. The dominant organisms are associated with the human microbiome and may include opportunistic pathogens. This study provides the first comprehensive catalog of both total and intact/viable bacteria and fungi found on surfaces in closed space systems and can be used to help develop safety measures that meet NASA requirements for deep space human habitation. The results of this study can have significant impact on our understanding of other confined built environments on the Earth such as clean rooms used in the pharmaceutical and medical industries.}, }
@article {pmid30946154, year = {2019}, author = {Sessa, L and Reddel, S and Manno, E and Quagliariello, A and Cotugno, N and Del Chierico, F and Amodio, D and Capponi, C and Leone, F and Bernardi, S and Rossi, P and Putignani, L and Palma, P}, title = {Distinct gut microbiota profile in antiretroviral therapy-treated perinatally HIV-infected patients associated with cardiac and inflammatory biomarkers.}, journal = {AIDS (London, England)}, volume = {33}, number = {6}, pages = {1001-1011}, doi = {10.1097/QAD.0000000000002131}, pmid = {30946154}, issn = {1473-5571}, abstract = {OBJECTIVE: Persistent inflammation and higher risk to develop cardiovascular diseases still represent a major complication for HIV-infected patients despite effective antiretroviral therapy (ART). We investigated the correlation between the gut microbiota profile, markers of inflammation, vascular endothelial activation (VEA) and microbial translocation (MT) in perinatally HIV-infected patients (PHIV) under ART.<br><br>DESIGN: Cross-sectional study including 61 ART-treated PHIV (age range 3-30 years old) and 71 age-matched healthy controls. Blood and stool sample were collected at the same time and analyzed for gut microbiota composition and plasma biomarkers.<br><br>METHODS: Gut microbiota composition was determined by 16S rRNA targeted-metagenomics. Soluble markers of MT, inflammation and VEA were quantified by ELISA or Luminex assay. Markers of immune activation were analyzed by flow cytometry on CD4 and CD8T cells.<br><br>RESULTS: We identified two distinct gut microbiota profiles (groups A and B) among PHIV. No different clinical parameters (age, sex, ethnicity, clinical class), dietary and sexual habits were found between the groups. The group A showed a relative dominance of Akkermansia muciniphila, whereas gut microbiota of group B was characterized by a higher biodiversity. The analysis of soluble markers revealed a significantly higher level of soluble E-selectine (P = 0.0296), intercellular adhesion molecule-1 (P = 0.0028), vascular adhesion molecule-1 (P = 0.0230), IL-6 (P = 0.0247) and soluble CD14 (P = 0.0142) in group A compared with group B.<br><br>CONCLUSION: Distinctive gut microbiota profiles are differently associated with inflammation, microbial translocation and VEA. Future studies are needed to understand the role of A. muciniphila and risk to develop cardiovascular diseases in PHIV.}, }
@article {pmid30942867, year = {2019}, author = {Brown, SM and Chen, H and Hao, Y and Laungani, BP and Ali, TA and Dong, C and Lijeron, C and Kim, B and Wultsch, C and Pei, Z and Krampis, K}, title = {MGS-Fast: Metagenomic shotgun data fast annotation using microbial gene catalogs.}, journal = {GigaScience}, volume = {8}, number = {4}, pages = {}, doi = {10.1093/gigascience/giz020}, pmid = {30942867}, issn = {2047-217X}, support = {UH3 CA140233/CA/NCI NIH HHS/United States ; UL1 TR000457/TR/NCATS NIH HHS/United States ; G12 MD007599/MD/NIMHD NIH HHS/United States ; R01 AI110372/AI/NIAID NIH HHS/United States ; U54 CA221705/CA/NCI NIH HHS/United States ; R01 CA159036/CA/NCI NIH HHS/United States ; R21 DE025352/DE/NIDCR NIH HHS/United States ; U01 CA182370/CA/NCI NIH HHS/United States ; }, abstract = {BACKGROUND: Current methods used for annotating metagenomics shotgun sequencing (MGS) data rely on a computationally intensive and low-stringency approach of mapping each read to a generic database of proteins or reference microbial genomes.<br><br>RESULTS: We developed MGS-Fast, an analysis approach for shotgun whole-genome metagenomic data utilizing Bowtie2 DNA-DNA alignment of reads that is an alternative to using the integrated catalog of reference genes database of well-annotated genes compiled from human microbiome data. This method is rapid and provides high-stringency matches (>90% DNA sequence identity) of the metagenomics reads to genes with annotated functions. We demonstrate the use of this method with data from a study of liver disease and synthetic reads, and Human Microbiome Project shotgun data, to detect differentially abundant Kyoto Encyclopedia of Genes and Genomes gene functions in these experiments. This rapid annotation method is freely available as a Galaxy workflow within a Docker image.<br><br>CONCLUSIONS: MGS-Fast can confidently transfer functional annotations from gene databases to metagenomic reads, with speed and accuracy.}, }
@article {pmid30939512, year = {2019}, author = {Chernikova, D and Yuan, I and Shaker, M}, title = {Prevention of allergy with diverse and healthy microbiota: an update.}, journal = {Current opinion in pediatrics}, volume = {}, number = {}, pages = {}, doi = {10.1097/MOP.0000000000000766}, pmid = {30939512}, issn = {1531-698X}, abstract = {PURPOSE OF REVIEW: Microbiota consist of symbiotic microscopic neighbors that interact on and within our bodies in diverse and incompletely understood ways throughout our lifetime. Though various associations with allergic disease have been described, clear effective therapeutic interventions to prevent allergy have been elusive.<br><br>RECENT FINDINGS: The human microbiome is influenced by multiple factors, including: mode of infant delivery (vaginal vs. cesarean section), breastfeeding, diet, presence of siblings and pets, exposure to antibiotics and other medications (particularly antacids), lifestyle, and developmental context. Microbial species promoting atopic responses and tolerance have been described. Specific microbiota likely act through distinct metabolic pathways to promote the health of their human hosts, optimally directing the developing immune system away from pro-allergic, Th2-dominated responses to more T-regulatory-influenced behaviors.<br><br>SUMMARY: Evidence suggests that specific healthy infant microbiome signatures may influence development of some components of the allergic march of childhood by decreasing atopic dermatitis, asthma, and food allergy. Further understanding of factors that influence healthy microbiota may lead to specific strategies tailored for early intervention and disease prevention.}, }
@article {pmid30938174, year = {2019}, author = {Sander, MA and Sander, MS and Isaac-Renton, JL and Croxen, MA}, title = {The Cutaneous Microbiome: Implications for Dermatology Practice.}, journal = {Journal of cutaneous medicine and surgery}, volume = {23}, number = {4}, pages = {436-441}, doi = {10.1177/1203475419839939}, pmid = {30938174}, issn = {1615-7109}, abstract = {The human integument is inhabited by a vast array of microorganisms known collectively as the cutaneous microbiome. As a result of advances in laboratory science, our understanding of the diversity and complexity of the human microbiome is rapidly evolving. In particular, advances in the field of genomics have enabled the study of the cutaneous microbiome with a hitherto unimaginable level of detail, resulting in a maturation of our understanding of cutaneous health and disease. Herein, we review current microbiology concepts and highlight the key features of recent laboratory advances, particularly with respect to genomics. We provide a summary of new findings related to normal skin flora, interactions between host immunity and microbial communities, and microbial relationships with common skin disorders. Finally, we review the implications for dermatologists.}, }
@article {pmid30937887, year = {2019}, author = {Sharma, A and Buschmann, MM and Gilbert, JA}, title = {Pharmacomicrobiomics: The Holy Grail to Variability in Drug Response?.}, journal = {Clinical pharmacology and therapeutics}, volume = {106}, number = {2}, pages = {317-328}, doi = {10.1002/cpt.1437}, pmid = {30937887}, issn = {1532-6535}, abstract = {The human body, with 3.0 × 1013 cells and more than 3.8 × 1013 microorganisms, has nearly a one-to-one ratio of resident microbes to human cells. Initiatives like the Human Microbiome Project, American Gut, and Flemish Gut have identified associations between microbial taxa and human health. The study of interactions between microbiome and pharmaceutical agents, i.e., pharmacomicrobiomics, has revealed an instrumental role of the microbiome in modulating drug response that alters the therapeutic outcomes. In this review, we present our current comprehension of the relationship of the microbiome, host biology, and pharmaceutical agents such as cardiovascular drugs, analgesics, and chemotherapeutic agents to human disease and treatment outcomes. We also discuss the significance of studying diet-gene-drug interactions and further address the key challenges associated with pharmacomicrobiomics. Finally, we examine proposed models employing systems biology for the application of pharmacomicrobiomics and other -omics data, and provide approaches to elucidate microbiome-drug interactions to improve future translation to personalized medicine.}, }
@article {pmid30935409, year = {2019}, author = {Hamidi, B and Wallace, K and Vasu, C and Alekseyenko, AV}, title = {W∗d -test: robust distance-based multivariate analysis of variance.}, journal = {Microbiome}, volume = {7}, number = {1}, pages = {51}, doi = {10.1186/s40168-019-0659-9}, pmid = {30935409}, issn = {2049-2618}, support = {U54 CA210962/CA/NCI NIH HHS/United States ; UL1 TR001450/TR/NCATS NIH HHS/United States ; }, mesh = {Computational Biology/*methods ; Computer Simulation ; Humans ; *Microbiota ; Multivariate Analysis ; Software ; }, abstract = {BACKGROUND: Community-wide analyses provide an essential means for evaluation of the effect of interventions or design variables on the composition of the microbiome. Applications of these analyses are omnipresent in microbiome literature, yet some of their statistical properties have not been tested for robustness towards common features of microbiome data. Recently, it has been reported that PERMANOVA can yield wrong results in the presence of heteroscedasticity and unbalanced sample sizes.<br><br>FINDINGS: We develop a method for multivariate analysis of variance, [Formula: see text], based on Welch MANOVA that is robust to heteroscedasticity in the data. We do so by extending a previously reported method that does the same for two-level independent factor variables. Our approach can accommodate multi-level factors, stratification, and multiple post hoc testing scenarios. An R language implementation of the method is available at https://github.com/alekseyenko/WdStar .<br><br>CONCLUSION: Our method resolves potential for confounding of location and dispersion effects in multivariate analyses by explicitly accounting for the differences in multivariate dispersion in the data tested. The methods based on [Formula: see text] have general applicability in microbiome and other 'omics data analyses.}, }
@article {pmid30935126, year = {2019}, author = {Massari, F and Mollica, V and Di Nunno, V and Gatto, L and Santoni, M and Scarpelli, M and Cimadamore, A and Lopez-Beltran, A and Cheng, L and Battelli, N and Montironi, R and Brandi, G}, title = {The Human Microbiota and Prostate Cancer: Friend or Foe?.}, journal = {Cancers}, volume = {11}, number = {4}, pages = {}, doi = {10.3390/cancers11040459}, pmid = {30935126}, issn = {2072-6694}, abstract = {The human microbiome is gaining increasing attention in the medical community, as knowledge on its role not only in health but also in disease development and response to therapies is expanding. Furthermore, the connection between the microbiota and cancer, especially the link between the gut microbiota and gastrointestinal tumors, is becoming clearer. The interaction between the microbiota and the response to chemotherapies and, more recently, to immunotherapy has been widely studied, and a connection between a peculiar type of microbiota and a better response to these therapies and a different incidence in toxicities has been hypothesized. As knowledge on the gut microbiota increases, interest in the residing microbial population in other systems of our body is also increasing. Consequently, the urinary microbiota is under evaluation for its possible implications in genitourinary diseases, including cancer. Prostate cancer is the most common cancer in the male population; thus, research regarding its etiology and possible factors correlated to disease progression or the response to specific therapies is thriving. This review has the purpose to recollect the current knowledge on the relationship between the human microbiota and prostate cancer.}, }
@article {pmid30935109, year = {2019}, author = {Nava Lara, RA and Aguilera-Mendoza, L and Brizuela, CA and Peña, A and Del Rio, G}, title = {Heterologous Machine Learning for the Identification of Antimicrobial Activity in Human-Targeted Drugs.}, journal = {Molecules (Basel, Switzerland)}, volume = {24}, number = {7}, pages = {}, doi = {10.3390/molecules24071258}, pmid = {30935109}, issn = {1420-3049}, support = {FOIN-219//Consejo Nacional de Ciencia y Tecnología/ ; CB-252316//Consejo Nacional de Ciencia y Tecnología/ ; IG100416//Programa de Apoyo a Proyectos de Investigación e Innovación Tecnológica, UNAM, Mexico/ ; IN208014//Programa de Apoyo a Proyectos de Investigación e Innovación Tecnológica, UNAM, Mexico/ ; }, mesh = {Anti-Infective Agents/*chemistry/*pharmacology ; Bacteria/drug effects ; *Drug Discovery/methods ; Gastrointestinal Microbiome/drug effects ; Humans ; *Machine Learning ; Microbial Sensitivity Tests ; }, abstract = {The emergence of microbes resistant to common antibiotics represent a current treat to human health. It has been recently recognized that non-antibiotic labeled drugs may promote antibiotic-resistance mechanisms in the human microbiome by presenting a secondary antibiotic activity; hence, the development of computer-assisted procedures to identify antibiotic activity in human-targeted compounds may assist in preventing the emergence of resistant microbes. In this regard, it is worth noting that while most antibiotics used to treat human infectious diseases are non-peptidic compounds, most known antimicrobials nowadays are peptides, therefore all computer-based models aimed to predict antimicrobials either use small datasets of non-peptidic compounds rendering predictions with poor reliability or they predict antimicrobial peptides that are not currently used in humans. Here we report a machine-learning-based approach trained to identify gut antimicrobial compounds; a unique aspect of our model is the use of heterologous training sets, in which peptide and non-peptide antimicrobial compounds were used to increase the size of the training data set. Our results show that combining peptide and non-peptide antimicrobial compounds rendered the best classification of gut antimicrobial compounds. Furthermore, this classification model was tested on the latest human-approved drugs expecting to identify antibiotics with broad-spectrum activity and our results show that the model rendered predictions consistent with current knowledge about broad-spectrum antibiotics. Therefore, heterologous machine learning rendered an efficient computational approach to classify antimicrobial compounds.}, }
@article {pmid30930963, year = {2018}, author = {Jaja-Chimedza, A and Zhang, L and Wolff, K and Graf, BL and Kuhn, P and Moskal, K and Carmouche, R and Newman, S and Salbaum, JM and Raskin, I}, title = {A dietary isothiocyanate-enriched moringa (Moringa oleifera) seed extract improves glucose tolerance in a high-fat-diet mouse model and modulates the gut microbiome.}, journal = {Journal of functional foods}, volume = {47}, number = {}, pages = {376-385}, doi = {10.1016/j.jff.2018.05.056}, pmid = {30930963}, issn = {1756-4646}, support = {P20 RR021945/RR/NCRR NIH HHS/United States ; P30 DK072476/DK/NIDDK NIH HHS/United States ; T32 AT004094/AT/NCCIH NIH HHS/United States ; P20 GM103528/GM/NIGMS NIH HHS/United States ; P50 AT002776/AT/NCCIH NIH HHS/United States ; P30 GM118430/GM/NIGMS NIH HHS/United States ; }, abstract = {Moringa oleifera (moringa) has been traditionally used for the treatment of diabetes and in water purification. We previously showed that moringa seed extract (MSE), standardized to its primary bioactive isothiocyanate (MIC-1), modulated inflammatory and antioxidant signaling pathways in vitro. To understand the efficacy and mechanisms of action of MSE in vivo, we incorporated MSE into the diets of normal and obese C57Bl/6J male mice fed a standard low-fat diet or a very high-fat diet for 12 wk, respectively. MSE supplementation resulted in reduced body weight, decreased adiposity, improved glucose tolerance, reduced inflammatory gene expression, and increased antioxidant gene expression. 16S rRNA gene sequencing and quantitative PCR of fecal/cecal samples showed major modulation of the gut microbial community and a significantly reduced bacterial load, similar to an antibiotic response. This suggests that MSE improves metabolic health by its intracellular anti-inflammatory and antioxidant activities, and/or its antibiotic-like restructuring of the gut microbiota.}, }
@article {pmid30930939, year = {2019}, author = {Guo, M and Xu, E and Ai, D}, title = {Inferring Bacterial Infiltration in Primary Colorectal Tumors From Host Whole Genome Sequencing Data.}, journal = {Frontiers in genetics}, volume = {10}, number = {}, pages = {213}, doi = {10.3389/fgene.2019.00213}, pmid = {30930939}, issn = {1664-8021}, abstract = {Colorectal cancer is the third most common cancer worldwide with abysmal survival, thus requiring novel therapy strategies. Numerous studies have frequently observed infiltrating bacteria within the primary tumor tissues derived from patients. These studies have implicated the relative abundance of these bacteria as a contributing factor in tumor progression. Infiltrating bacteria are believed to be among the major drivers of tumorigenesis, progression, and metastasis and, hence, promising targets for new treatments. However, measuring their abundance directly remains challenging. One potential approach is to use the unmapped reads of host whole genome sequencing (hWGS) data, which previous studies have considered as contaminants and discarded. Here, we developed rigorous bioinformatics and statistical procedures to identify tumor-infiltrating bacteria associated with colorectal cancer from such whole genome sequencing data. Our approach used the reads of whole genome sequencing data of colon adenocarcinoma tissues not mapped to the human reference genome, including unmapped paired-end read pairs and single-end reads, the mates of which were mapped. We assembled the unmapped read pairs, remapped all those reads to the collection of human microbiome reference, and then computed their relative abundance of microbes by maximum likelihood (ML) estimation. We analyzed and compared the relative abundance and diversity of infiltrating bacteria between primary tumor tissues and associated normal blood samples. Our results showed that primary tumor tissues contained far more diverse total infiltrating bacteria than normal blood samples. The relative abundance of Bacteroides fragilis, Bacteroides dorei, and Fusobacterium nucleatum was significantly higher in primary colorectal tumors. These three bacteria were among the top ten microbes in the primary tumor tissues, yet were rarely found in normal blood samples. As a validation step, most of these bacteria were also closely associated with colorectal cancer in previous studies with alternative approaches. In summary, our approach provides a new analytic technique for investigating the infiltrating bacterial community within tumor tissues. Our novel cloud-based bioinformatics and statistical pipelines to analyze the infiltrating bacteria in colorectal tumors using the unmapped reads of whole genome sequences can be freely accessed from GitHub at https://github.com/gutmicrobes/UMIB.git.}, }
@article {pmid30930863, year = {2019}, author = {Reid, G and Gadir, AA and Dhir, R}, title = {Probiotics: Reiterating What They Are and What They Are Not.}, journal = {Frontiers in microbiology}, volume = {10}, number = {}, pages = {424}, doi = {10.3389/fmicb.2019.00424}, pmid = {30930863}, issn = {1664-302X}, abstract = {It has been over seventeen years since the scientific definition of probiotics was crafted, along with guidelines ensuring the appropriate use of the term. This definition is now used globally, yet on a consistent basis scientists, media and industry misrepresent probiotics or make generalized statements that illustrate a misunderstanding of their utility and limitations. The rate of discovery of novel organisms with potentially therapeutic benefit for both human and environmental health is progressing at an unprecedented rate. However, the term &quot;probiotic&quot; is often misapplied to describe any microbe with plausible therapeutic utility in the human host. It is argued that strict compliance to the scientific definition of the term &quot;probiotic&quot; and avoidance of generalizations to the whole field of probiotics based upon studies of one product, will help advance the development and validation of microbial therapies, and applications to improve human health.}, }
@article {pmid30925932, year = {2019}, author = {van der Veer, C and Hertzberger, RY and Bruisten, SM and Tytgat, HLP and Swanenburg, J and de Kat Angelino-Bart, A and Schuren, F and Molenaar, D and Reid, G and de Vries, H and Kort, R}, title = {Comparative genomics of human Lactobacillus crispatus isolates reveals genes for glycosylation and glycogen degradation: implications for in vivo dominance of the vaginal microbiota.}, journal = {Microbiome}, volume = {7}, number = {1}, pages = {49}, doi = {10.1186/s40168-019-0667-9}, pmid = {30925932}, issn = {2049-2618}, mesh = {Bacterial Proteins/genetics ; Dysbiosis/*microbiology ; Female ; Genome, Bacterial ; Genomics/*methods ; Glycogen/*metabolism ; Glycosylation ; Glycosyltransferases/genetics ; Humans ; Lactobacillus crispatus/genetics/*isolation &amp; purification/metabolism ; Neisseria gonorrhoeae/growth &amp; development ; Phenotype ; Phylogeny ; Sequence Analysis, DNA ; Vagina/*microbiology ; }, abstract = {BACKGROUND: A vaginal microbiota dominated by lactobacilli (particularly Lactobacillus crispatus) is associated with vaginal health, whereas a vaginal microbiota not dominated by lactobacilli is considered dysbiotic. Here we investigated whether L. crispatus strains isolated from the vaginal tract of women with Lactobacillus-dominated vaginal microbiota (LVM) are pheno- or genotypically distinct from L. crispatus strains isolated from vaginal samples with dysbiotic vaginal microbiota (DVM).<br><br>RESULTS: We studied 33 L. crispatus strains (n = 16 from LVM; n = 17 from DVM). Comparison of these two groups of strains showed that, although strain differences existed, both groups degraded various carbohydrates, produced similar amounts of organic acids, inhibited Neisseria gonorrhoeae growth, and did not produce biofilms. Comparative genomics analyses of 28 strains (n = 12 LVM; n = 16 DVM) revealed a novel, 3-fragmented glycosyltransferase gene that was more prevalent among strains isolated from DVM. Most L. crispatus strains showed growth on glycogen-supplemented growth media. Strains that showed less-efficient (n = 6) or no (n = 1) growth on glycogen all carried N-terminal deletions (respectively, 29 and 37 amino acid deletions) in a putative pullulanase type I protein.<br><br>DISCUSSION: L. crispatus strains isolated from LVM were not phenotypically distinct from L. crispatus strains isolated from DVM; however, the finding that the latter were more likely to carry a 3-fragmented glycosyltransferase gene may indicate a role for cell surface glycoconjugates, which may shape vaginal microbiota-host interactions. Furthermore, the observation that variation in the pullulanase type I gene is associated with growth on glycogen discourages previous claims that L. crispatus cannot directly utilize glycogen.}, }
@article {pmid30923584, year = {2018}, author = {Li, Z and Lee, K and Karagas, MR and Madan, JC and Hoen, AG and O'Malley, AJ and Li, H}, title = {Conditional Regression Based on a Multivariate Zero-Inflated Logistic-Normal Model for Microbiome Relative Abundance Data.}, journal = {Statistics in biosciences}, volume = {10}, number = {3}, pages = {587-608}, doi = {10.1007/s12561-018-9219-2}, pmid = {30923584}, issn = {1867-1764}, support = {R01 GM123056/GM/NIGMS NIH HHS/United States ; UH3 OD023275/OD/NIH HHS/United States ; R01 GM123014/GM/NIGMS NIH HHS/United States ; R01 LM012723/LM/NLM NIH HHS/United States ; K01 LM011985/LM/NLM NIH HHS/United States ; P01 ES022832/ES/NIEHS NIH HHS/United States ; UG3 OD023275/OD/NIH HHS/United States ; R01 CA127334/CA/NCI NIH HHS/United States ; P20 GM104416/GM/NIGMS NIH HHS/United States ; }, abstract = {The human microbiome plays critical roles in human health and has been linked to many diseases. While advanced sequencing technologies can characterize the composition of the microbiome in unprecedented detail, it remains challenging to disentangle the complex interplay between human microbiome and disease risk factors due to the complicated nature of microbiome data. Excessive numbers e f zero values, high dimensionality, the hierarchical phylogenetic tree and compositional structure are compounded and consequently make existing methods inadequate to appropriately address these issues. We propose a multivariate two-part zero-inflated logistic normal (MZILN) model to analyze the association of disease risk factors with individual microbial taxa and overall microbial community composition. This approach can naturally handle excessive numbers e f zeros and the compositional data structure with the discrete part and the logistic-normal part e f the model. For parameter estimation, an estimating equations approach is employed that enables us to address the complex inter-taxa correlation structure induced by the hierarchical phylogenetic tree structure and the compositional data structure. This model is able to incorporate standard regularization approaches to deal with high dimensionality. Simulation shews that our model outperforms existing methods. Our approach is also compared to ethers using the analysis of real microbiome data.}, }
@article {pmid30919073, year = {2019}, author = {Ames, NJ and Barb, JJ and Ranucci, A and Kim, H and Mudra, SE and Cashion, AK and Townsley, DM and Childs, R and Paster, BJ and Faller, LL and Wallen, GR}, title = {The oral microbiome of patients undergoing treatment for severe aplastic anemia: a pilot study.}, journal = {Annals of hematology}, volume = {98}, number = {6}, pages = {1351-1365}, doi = {10.1007/s00277-019-03599-w}, pmid = {30919073}, issn = {1432-0584}, mesh = {Adult ; Aged ; Anemia, Aplastic/drug therapy/*microbiology/therapy ; Anti-Bacterial Agents/pharmacology ; Antilymphocyte Serum/therapeutic use ; Benzoates/pharmacology/therapeutic use ; Biodiversity ; Cyclosporine/therapeutic use ; DNA, Bacterial/analysis ; Dental Health Surveys ; Female ; Graft vs Host Disease/etiology/microbiology ; Hematopoietic Stem Cell Transplantation ; Humans ; Hydrazines/pharmacology/therapeutic use ; Immunocompromised Host ; Immunosuppressive Agents/therapeutic use ; Male ; *Microbiota/drug effects ; Middle Aged ; Mouth/*microbiology ; Pilot Projects ; Pyrazoles/pharmacology/therapeutic use ; Ribotyping ; Sequence Analysis, DNA ; Smoking/epidemiology ; T-Lymphocytes/immunology ; Tongue/microbiology ; Young Adult ; }, abstract = {The microbiome, an intriguing component of the human body, composed of trillions of microorganisms, has prompted scientific exploration to identify and understand its function and role in health and disease. As associations between microbiome composition, disease, and symptoms accumulate, the future of medicine hinges upon a comprehensive knowledge of these microorganisms for patient care. The oral microbiome may provide valuable and efficient insight for predicting future changes in disease status, infection, or treatment course. The main aim of this pilot study was to characterize the oral microbiome in patients with severe aplastic anemia (SAA) during their therapeutic course. SAA is a hematologic disease characterized by bone marrow failure which if untreated is fatal. Treatment includes either hematopoietic stem cell transplantation (HSCT) or immunosuppressive therapy (IST). In this study, we examined the oral microbiome composition of 24 patients admitted to the National Institutes of Health (NIH) Clinical Center for experimental SAA treatment. Tongue brushings were collected to assess the effects of treatment on the oral microbiome. Twenty patients received standard IST (equine antithymocyte globulin and cyclosporine) plus eltrombopag. Four patients underwent HSCT. Oral specimens were obtained at three time points during treatment and clinical follow-up. Using a novel approach to 16S rRNA gene sequence analysis encompassing seven hypervariable regions, results demonstrated a predictable decrease in microbial diversity over time among the transplant patients. Linear discriminant analysis or LefSe reported a total of 14 statistically significant taxa (p < 0.05) across time points in the HSCT patients. One-way plots of relative abundance for two bacterial species (Haemophilus parainfluenzae and Rothia mucilaginosa) in the HSCT group, show the differences in abundance between time points. Only one bacterial species (Prevotella histicola) was noted in the IST group with a p value of 0.065. The patients receiving immunosuppressive therapy did not exhibit a clear change in diversity over time; however, patient-specific changes were noted. In addition, we compared our findings to tongue dorsum samples from healthy participants in the Human Microbiome Project (HMP) database and found among HSCT patients, approximately 35% of bacterial identifiers (N = 229) were unique to this study population and were not present in tongue dorsum specimens obtained from the HMP. Among IST-treated patients, 45% (N = 351) were unique to these patients and not identified by the HMP. Although antibiotic use may have likely influenced bacterial composition and diversity, some literature suggests a decreased impact of antimicrobials on the oral microbiome as compared to their effect on the gut microbiome. Future studies with larger sample sizes that focus on the oral microbiome and the effects of antibiotics in an immunosuppressed patient population may help establish these potential associations.}, }
@article {pmid30918980, year = {2019}, author = {Shannon, MB and Limeira, R and Johansen, D and Gao, X and Lin, H and Dong, Q and Wolfe, AJ and Mueller, ER}, title = {Bladder urinary oxygen tension is correlated with urinary microbiota composition.}, journal = {International urogynecology journal}, volume = {30}, number = {8}, pages = {1261-1267}, doi = {10.1007/s00192-019-03931-y}, pmid = {30918980}, issn = {1433-3023}, abstract = {INTRODUCTION AND HYPOTHESIS: Presence of microbial communities (microbiota) in an organ system depends on environmental factors, such as oxygen availability. We describe a novel technique to measure bladder urine oxygen tension (BUOT) in ambulatory women and use that technique to compare BUOT values to female urinary microbiota and participant urinary signs and symptoms.<br><br>METHODS: Ambulatory female urogynecology patients presenting for clinical care who were willing to undergo transurethral catheterization underwent BUOT determination with a non-invasive flow-through oxygen sensor. To detect urinary microbiota in the bladder, 16S rRNA gene sequencing was performed on catheterized urine. Multivariate statistical analyses were performed to examine potential correlations among BUOT, urinary microbiota compositions and clinical variables.<br><br>RESULTS: Significant variation in BUOT existed between individuals (range: 0.47-51.5 mmHg; median: 23.1 ± 13.5). Microbiota compositions were associated with BUOT (p = 0.03). BUOT was significantly lower in urines that were nitrite negative on dipstick analysis (p = 0.0001) and in participants who answered yes to having urinary leakage on the validated Urinary Distress Inventory (p = 0.01).<br><br>CONCLUSIONS: BUOTs can be measured in ambulatory women. For urogynecology patients, a wide range of values exist. BUOT may be associated with the presence of urinary microbiota and resultant signs and symptoms.}, }
@article {pmid30917589, year = {2019}, author = {George, A}, title = {Antimicrobial Resistance (AMR) in the Food Chain: Trade, One Health and Codex.}, journal = {Tropical medicine and infectious disease}, volume = {4}, number = {1}, pages = {}, doi = {10.3390/tropicalmed4010054}, pmid = {30917589}, issn = {2414-6366}, abstract = {Strategies that take on a One Health approach to addressing antimicrobial resistance (AMR) focused on reducing human use of antimicrobials, but policy-makers now have to grapple with a different set of political, economic, and highly sensitive trade interests less amenable to government direction, to tackle AMR in the food chain. Understanding the importance and influence of the intergovernmental Codex negotiations underway on AMR in the Food Chain is very weak but essential for AMR public policy experts. National and global food producing industries are already under pressure as consumers learn about the use of antimicrobials in food production and more so when the full impact of AMR microorganisms in the food chain and on the human microbiome is better understood. Governments will be expected to respond. Trade-related negotiations on access and use made of antimicrobials is political: the relevance of AMR 'evidence' is already contested and not all food producers or users of antimicrobials in the food chain are prepared to, or capable of, moving at the same pace. In trade negotiations governments defend their interpretation of national interest. Given AMR in the global food chain threatens national interest, both AMR One Health and zoonotic disease experts should understand and participate in all trade-related AMR negotiations to protect One Health priorities. To help facilitate this an overview and analysis of Codex negotiations is provided.}, }
@article {pmid30911403, year = {2019}, author = {El-Awady, A and de Sousa Rabelo, M and Meghil, MM and Rajendran, M and Elashiry, M and Stadler, AF and Foz, AM and Susin, C and Romito, GA and Arce, RM and Cutler, CW}, title = {Polymicrobial synergy within oral biofilm promotes invasion of dendritic cells and survival of consortia members.}, journal = {NPJ biofilms and microbiomes}, volume = {5}, number = {}, pages = {11}, doi = {10.1038/s41522-019-0084-7}, pmid = {30911403}, issn = {2055-5008}, support = {R01 DE014328/DE/NIDCR NIH HHS/United States ; }, abstract = {Years of human microbiome research have confirmed that microbes rarely live or function alone, favoring diverse communities. Yet most experimental host-pathogen studies employ single species models of infection. Here, the influence of three-species oral microbial consortium on growth, virulence, invasion and persistence in dendritic cells (DCs) was examined experimentally in human monocyte-derived dendritic cells (DCs) and in patients with periodontitis (PD). Cooperative biofilm formation by Streptococcus gordonii, Fusobacterium nucleatum and Porphyromonas gingivalis was documented in vitro using growth models and scanning electron microscopy. Analysis of growth rates by species-specific 16s rRNA probes revealed distinct, early advantages to consortium growth for S. gordonii and F. nucleatum with P. gingivalis, while P. gingivalis upregulated its short mfa1 fimbriae, leading to increased invasion of DCs. F. nucleatum was only taken up by DCs when in consortium with P. gingivalis. Mature consortium regressed DC maturation upon uptake, as determined by flow cytometry. Analysis of dental plaques of PD and healthy subjects by 16s rRNA confirmed oral colonization with consortium members, but DC hematogenous spread was limited to P. gingivalis and F. nucleatum. Expression of P. gingivalis mfa1 fimbriae was increased in dental plaques and hematogenous DCs of PD patients. P. gingivalis in the consortium correlated with an adverse clinical response in the gingiva of PD subjects. In conclusion, we have identified polymicrobial synergy in a three-species oral consortium that may have negative consequences for the host, including microbial dissemination and adverse peripheral inflammatory responses.}, }
@article {pmid30911128, year = {2019}, author = {Brito, IL and Gurry, T and Zhao, S and Huang, K and Young, SK and Shea, TP and Naisilisili, W and Jenkins, AP and Jupiter, SD and Gevers, D and Alm, EJ}, title = {Transmission of human-associated microbiota along family and social networks.}, journal = {Nature microbiology}, volume = {4}, number = {6}, pages = {964-971}, doi = {10.1038/s41564-019-0409-6}, pmid = {30911128}, issn = {2058-5276}, mesh = {Bacteria/genetics ; *Family ; Female ; Fiji ; Gastrointestinal Microbiome/genetics ; Genomics ; Genotype ; Host Specificity ; Humans ; Interspersed Repetitive Sequences ; Male ; *Microbiota/genetics ; Polymorphism, Single Nucleotide ; *Social Networking ; }, abstract = {The human microbiome, described as an accessory organ because of the crucial functions it provides, is composed of species that are uniquely found in humans1,2. Yet, surprisingly little is known about the impact of routine interpersonal contacts in shaping microbiome composition. In a relatively 'closed' cohort of 287 people from the Fiji Islands, where common barriers to bacterial transmission are absent, we examine putative bacterial transmission in individuals' gut and oral microbiomes using strain-level data from both core single-nucleotide polymorphisms and flexible genomic regions. We find a weak signal of transmission, defined by the inferred sharing of genotypes, across many organisms that, in aggregate, reveals strong transmission patterns, most notably within households and between spouses. We were unable to determine the directionality of transmission nor whether it was direct. We further find that women harbour strains more closely related to those harboured by their familial and social contacts than men, and that transmission patterns of oral-associated and gut-associated microbiota need not be the same. Using strain-level data alone, we are able to confidently predict a subset of spouses, highlighting the role of shared susceptibilities, behaviours or social interactions that distinguish specific links in the social network.}, }
@article {pmid30910274, year = {2019}, author = {Leynaert, B and Le Moual, N and Neukirch, C and Siroux, V and Varraso, R}, title = {[Environmental risk factors for asthma developement].}, journal = {Presse medicale (Paris, France : 1983)}, volume = {48}, number = {3 Pt 1}, pages = {262-273}, doi = {10.1016/j.lpm.2019.02.022}, pmid = {30910274}, issn = {2213-0276}, mesh = {Air Pollution, Indoor/adverse effects ; Allergens/adverse effects ; Animals ; Asthma/*etiology/microbiology ; Environmental Exposure/*adverse effects ; Humans ; Risk Factors ; }, abstract = {The prevalence of asthma has increased rapidly since the early 1970s, and only changes in exposure to environmental factors; which go together with changes in lifestyle, are likely to explain such a rapid increase. Exposure to allergens is a risk factor for allergic sensitization, and allergic sensitization is a risk factor for allergic asthma. However, apart from indoor mold exposure as a risk factor for childhood asthma, there is insufficient evidence to conclude that the associations between allergen exposure and asthma development are causal. A new challenge for research is to analyze the huge amount of data derived from the metagenomic characterization of the environmental and human microbiome, to understand the role of interactions between viruses, bacteria and allergens in the development of asthma. It is recognized that prenatal and postnatal exposure to air pollution and maternal smoking increase the risk of developing asthma in children. In adults, the data are scarce and the results remain controversial as regards these exposures and asthma incidence. Further research is needed to appraise the effect of exposure to phenols, phthalates and perfluorinated compounds, which are widespread in the environment and may be associated with asthma, especially in children. Frequent use of chemicals for home cleaning especially in the form of sprays - which is a common practice at the population level - is a risk factor for the development of adult asthma. The domestic use of cleaning products might also be a risk factor for asthma in children exposed at home. The chemicals involved in these relationships are still to be identified. Occupational asthma is a major phenotype of adult asthma. A significant part of these asthma cases might relate to occupational exposure to cleaning products. While there is evidence of associations between diet during pregnancy or during childhood and the risk of developing asthma in children, the data in adults are insufficient. Beyond genetic factors, body composition is influenced by dietary choices and physical activity. Further research is needed to clarify the complex interplay between these nutritional factors and asthma development. The new challenge for research is to decipher the role of all the environmental factors to which the individual is exposed since conception (&quot;exposome&quot;) in the development of asthma, using a holistic approach.}, }
@article {pmid30908947, year = {2019}, author = {Ahern, GJ and Hennessy, AA and Ryan, CA and Ross, RP and Stanton, C}, title = {Advances in Infant Formula Science.}, journal = {Annual review of food science and technology}, volume = {10}, number = {}, pages = {75-102}, doi = {10.1146/annurev-food-081318-104308}, pmid = {30908947}, issn = {1941-1421}, abstract = {Human milk contains a plethora of nutrients and bioactive components to help nourish the developing neonate and is considered the &quot;gold standard&quot; for early life nutrition-as befits the only food &quot;designed&quot; by evolution to feed human infants. Over the past decade, there is considerable evidence that highlights the &quot;intelligence&quot; contained in milk components that contribute to infant health beyond basic nutrition-in areas such as programming the developing microbiome and immune system and protecting against infection. Such discoveries have led to new opportunities for infant milk formula (IMF) manufacturers to refine nutritional content in order to simulate the functionality of breast milk. These include the addition of specialized protein fractions as well as fatty acid and complex carbohydrate components-all of which have mechanistic supporting evidence in terms of improving the health and nutrition of the infant. Moreover, IMF is the single most important dietary intervention whereby the human microbiome can be influenced at a crucial early stage of development. In this respect, it is expected that the complexity of IMF will continue to increase as we get a greater understanding of how it can modulate microbiota development (including the development of probiotics, prebiotics, and synbiotics) and influence long-term health. This review provides a scientific evaluation of key features of importance to infant nutrition, including differences in milk composition and emerging &quot;humanized&quot; ingredients.}, }
@article {pmid30899033, year = {2019}, author = {Reddel, S and Del Chierico, F and Quagliariello, A and Giancristoforo, S and Vernocchi, P and Russo, A and Fiocchi, A and Rossi, P and Putignani, L and El Hachem, M}, title = {Gut microbiota profile in children affected by atopic dermatitis and evaluation of intestinal persistence of a probiotic mixture.}, journal = {Scientific reports}, volume = {9}, number = {1}, pages = {4996}, doi = {10.1038/s41598-019-41149-6}, pmid = {30899033}, issn = {2045-2322}, support = {201502P003534//Ministero della Salute (Ministry of Health, Italy)/ ; 201602P00370//Ministero della Salute (Ministry of Health, Italy)/ ; 201503X003570//Ministero della Salute (Ministry of Health, Italy)/ ; }, abstract = {Atopic dermatitis (AD) has been hypothesised to be associated with gut microbiota (GM) composition. We performed a comparative study of the GM profile of 19 AD children and 18 healthy individuals aimed at identifying bacterial biomarkers associated with the disease. The effect of probiotic intake (Bifidobacterium breve plus Lactobacillus salivarius) on the modulation of GM and the probiotic persistence in the GM were also evaluated. Faecal samples were analysed by real-time PCR and 16S rRNA targeted metagenomics. Although the probiotics, chosen for this study, did not shape the entire GM profile, we observed the ability of these species to pass through the gastrointestinal tract and to persist (only B. breve) in the GM. Moreover, the GM of patients compared to CTRLs showed a dysbiotic status characterised by an increase of Faecalibacterium, Oscillospira, Bacteroides, Parabacteroides and Sutterella and a reduction of short-chain fatty acid (SCFA)-producing bacteria (i.e., Bifidobacterium, Blautia, Coprococcus, Eubacterium and Propionibacterium). Taken togheter these results show an alteration in AD microbiota composition with the depletion or absence of some species, opening the way to future probiotic intervention studies.}, }
@article {pmid30895406, year = {2019}, author = {Nguyen, VD and Nguyen, TT and Pham, TT and Packianather, M and Le, CH}, title = {Molecular screening and genetic diversity analysis of anticancer Azurin-encoding and Azurin-like genes in human gut microbiome deduced through cultivation-dependent and cultivation-independent studies.}, journal = {International microbiology : the official journal of the Spanish Society for Microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1007/s10123-019-00070-8}, pmid = {30895406}, issn = {1618-1905}, support = {106-YS.04-2014.40//National Foundation for Science and Technology Development/ ; }, abstract = {Azurin, a bacteriocin produced by a human gut bacterium Pseudomonas aeruginosa, can reveal selectively cytotoxic and induce apoptosis in cancer cells. After overcoming two phase I trials, a functional region of Azurin called p28 has been approved as a drug for the treatment of brain tumor glioma by FDA. The present study aims to improve a screening procedure and assess genetic diversity of Azurin genes in P. aeruginosa and Azurin-like genes in the gut microbiome of a specific population in Vietnam and global populations. Firstly, both cultivation-dependent and cultivation-independent techniques based on genomic and metagenomic DNAs extracted from fecal samples of the healthy specific population were performed and optimized to detect Azurin genes. Secondly, the Azurin gene sequences were analyzed and compared with global populations by using bioinformatics tools. Finally, the screening procedure improved from the first step was applied for screening Azurin-like genes, followed by the protein synthesis and NCI in vitro screening for anticancer activity. As a result, this study has successfully optimized the annealing temperatures to amplify DNAs for screening Azurin genes and applying to Azurin-like genes from human gut microbiota. The novelty of this study is the first of its kind to classify Azurin genes into five different genotypes at a global scale and confirm the potential anticancer activity of three Azurin-like synthetic proteins (Cnazu1, Dlazu11, and Ruazu12). The results contribute to the procedure development applied for screening anticancer proteins from human microbiome and a comprehensive understanding of their therapeutic response at a genetic level.}, }
@article {pmid30894847, year = {2019}, author = {Brown, EEF and Cooper, A and Carrillo, C and Blais, B}, title = {Selection of Multidrug-Resistant Bacteria in Medicated Animal Feeds.}, journal = {Frontiers in microbiology}, volume = {10}, number = {}, pages = {456}, doi = {10.3389/fmicb.2019.00456}, pmid = {30894847}, issn = {1664-302X}, abstract = {Exposure to antimicrobial resistant (AMR) bacteria is a major public health issue which may, in part, have roots in food production practices that are conducive to the selection of AMR bacteria ultimately impacting the human microbiome through food consumption. Of particular concern is the prophylactic use of antibiotics in animal husbandry, such as the medication of feeds with sulfonamides and other antibiotics not considered clinically relevant, but which may nonetheless co-select for multi-drug resistant (MDR) bacteria harboring resistance to medically important antibiotics. Using a MDR Klebsiella pneumoniae strain exhibiting resistance to sulfonamides and beta-lactams (including carbapenem) as a model, we examined the ability of non-medicated and commercially medicated (sulfonamide) animal feeds to select for the model strain when inoculated at low levels by measuring its recovery along with key AMR markers, sul1(sulfonamide) and blaKPC-3 (meropenem), under different incubation conditions. When non-medicated feeds were supplemented with defined amounts of sulfadiazine the model strain was significantly enriched after incubation in Mueller Hinton Broth at 37°C overnight, or in same at room temperature for a week, with consistent detection of both the sul1 and blaKPC-3 markers as determined by polymerase chain reaction (PCR) techniques to screen colony isolates recovered on plating media. Significant recoveries of the inoculated strain and the sul1 and blaKPC-3 markers were observed with one of three commercially medicated (sulfamethazine) feeds tested under various incubation conditions. These results demonstrate that under certain conditions the prophylactic use of so-called non-priority antibiotics in feeds can potentially lead to co-selection of environmental AMR bacteria with resistance to medically important antibiotics, which may have far-reaching implications for human health.}, }
@article {pmid30894688, year = {2019}, author = {Ma, ZS and Li, L and Gotelli, NJ}, title = {Diversity-disease relationships and shared species analyses for human microbiome-associated diseases.}, journal = {The ISME journal}, volume = {13}, number = {8}, pages = {1911-1919}, doi = {10.1038/s41396-019-0395-y}, pmid = {30894688}, issn = {1751-7370}, abstract = {Diversity indices have been routinely computed in the study of human microbiome-associated diseases (MADs). However, it is still unclear whether there is a consistent diversity-disease relationship (DDR) for the human MADs, and whether there are consistent differences in the taxonomic composition of microbiomes sampled from healthy versus diseased individuals. Here we reanalyzed raw data and used a meta-analysis to compare the microbiome diversity and composition of healthy versus diseased individuals in 41 comparisons extracted from 27 previously published studies of human MADs. In the DDR analysis, the average effect size across studies did not differ from zero for a comparison of healthy versus diseased individuals. In 30 of 41 comparisons (73%) there was no significant difference in microbiome diversity of healthy versus diseased individuals, or of different disease classes. For the species composition analysis (shared species analysis), the effect sizes were significantly different from zero. In 33 of 41 comparisons (80%), there were fewer OTUs (operational taxonomic units) shared between healthy and diseased individuals than expected by chance, but with 49% (20 of 41 comparisons) statistically significant. These results imply that the taxonomic composition of disease-associated microbiomes is often distinct from that of healthy individuals. Because species composition changes with disease state, some microbiome OTUs may serve as potential diagnostic indicators of disease. However, the overall species diversity of human microbiomes is not a reliable indicator of disease.}, }
@article {pmid30890301, year = {2019}, author = {Chen, QL and Cui, HL and Su, JQ and Penuelas, J and Zhu, YG}, title = {Antibiotic Resistomes in Plant Microbiomes.}, journal = {Trends in plant science}, volume = {24}, number = {6}, pages = {530-541}, doi = {10.1016/j.tplants.2019.02.010}, pmid = {30890301}, issn = {1878-4372}, abstract = {Microorganisms associated with plants may alter the traits of the human microbiome important for human health, but this alteration has largely been overlooked. The plant microbiome is an interface between plants and the environment, and provides many ecosystem functions such as improving nutrient uptake and protecting against biotic and abiotic stress. The plant microbiome also represents a major pathway by which humans are exposed to microbes and genes consumed with food, such as pathogenic bacteria, antibiotic-resistant bacteria, and antibiotic-resistance genes. In this review we highlight the main findings on the composition and function of the plant microbiome, and underline the potential of plant microbiomes in the dissemination of antibiotic resistance via food consumption or direct contact.}, }
@article {pmid30890187, year = {2019}, author = {Tovaglieri, A and Sontheimer-Phelps, A and Geirnaert, A and Prantil-Baun, R and Camacho, DM and Chou, DB and Jalili-Firoozinezhad, S and de Wouters, T and Kasendra, M and Super, M and Cartwright, MJ and Richmond, CA and Breault, DT and Lacroix, C and Ingber, DE}, title = {Species-specific enhancement of enterohemorrhagic E. coli pathogenesis mediated by microbiome metabolites.}, journal = {Microbiome}, volume = {7}, number = {1}, pages = {43}, doi = {10.1186/s40168-019-0650-5}, pmid = {30890187}, issn = {2049-2618}, support = {K08 DK106562/DK/NIDDK NIH HHS/United States ; T32 CA009216/CA/NCI NIH HHS/United States ; R01 DK084056/DK/NIDDK NIH HHS/United States ; P30 DK034854/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Bacteria/*metabolism ; Benzoates/pharmacology ; Caproates/pharmacology ; Cells, Cultured ; Enterohemorrhagic Escherichia coli/metabolism/*pathogenicity ; Escherichia coli Infections/microbiology/*pathology ; Female ; Gastrointestinal Microbiome ; Heptanoic Acids/pharmacology ; Humans ; Intestines/*cytology/microbiology ; Male ; Mice ; Microchip Analytical Procedures ; Organ Culture Techniques/*methods ; Species Specificity ; }, abstract = {BACKGROUND: Species-specific differences in tolerance to infection are exemplified by the high susceptibility of humans to enterohemorrhagic Escherichia coli (EHEC) infection, whereas mice are relatively resistant to this pathogen. This intrinsic species-specific difference in EHEC infection limits the translation of murine research to human. Furthermore, studying the mechanisms underlying this differential susceptibility is a difficult problem due to complex in vivo interactions between the host, pathogen, and disparate commensal microbial communities.<br><br>RESULTS: We utilize organ-on-a-chip (Organ Chip) microfluidic culture technology to model damage of the human colonic epithelium induced by EHEC infection, and show that epithelial injury is greater when exposed to metabolites derived from the human gut microbiome compared to mouse. Using a multi-omics approach, we discovered four human microbiome metabolites-4-methyl benzoic acid, 3,4-dimethylbenzoic acid, hexanoic acid, and heptanoic acid-that are sufficient to mediate this effect. The active human microbiome metabolites preferentially induce expression of flagellin, a bacterial protein associated with motility of EHEC and increased epithelial injury. Thus, the decreased tolerance to infection observed in humans versus other species may be due in part to the presence of compounds produced by the human intestinal microbiome that actively promote bacterial pathogenicity.<br><br>CONCLUSION: Organ-on-chip technology allowed the identification of specific human microbiome metabolites modulating EHEC pathogenesis. These identified metabolites are sufficient to increase susceptibility to EHEC in our human Colon Chip model and they contribute to species-specific tolerance. This work suggests that higher concentrations of these metabolites could be the reason for higher susceptibility to EHEC infection in certain human populations, such as children. Furthermore, this research lays the foundation for therapeutic-modulation of microbe products in order to prevent and treat human bacterial infection.}, }
@article {pmid30885720, year = {2019}, author = {LaPierre, N and Ju, CJ and Zhou, G and Wang, W}, title = {MetaPheno: A critical evaluation of deep learning and machine learning in metagenome-based disease prediction.}, journal = {Methods (San Diego, Calif.)}, volume = {166}, number = {}, pages = {74-82}, doi = {10.1016/j.ymeth.2019.03.003}, pmid = {30885720}, issn = {1095-9130}, support = {R01 GM115833/GM/NIGMS NIH HHS/United States ; T32 EB016640/EB/NIBIB NIH HHS/United States ; }, abstract = {The human microbiome plays a number of critical roles, impacting almost every aspect of human health and well-being. Conditions in the microbiome have been linked to a number of significant diseases. Additionally, revolutions in sequencing technology have led to a rapid increase in publicly-available sequencing data. Consequently, there have been growing efforts to predict disease status from metagenomic sequencing data, with a proliferation of new approaches in the last few years. Some of these efforts have explored utilizing a powerful form of machine learning called deep learning, which has been applied successfully in several biological domains. Here, we review some of these methods and the algorithms that they are based on, with a particular focus on deep learning methods. We also perform a deeper analysis of Type 2 Diabetes and obesity datasets that have eluded improved results, using a variety of machine learning and feature extraction methods. We conclude by offering perspectives on study design considerations that may impact results and future directions the field can take to improve results and offer more valuable conclusions. The scripts and extracted features for the analyses conducted in this paper are available via GitHub:https://github.com/nlapier2/metapheno.}, }
@article {pmid30880022, year = {2019}, author = {Cohen, LJ and Cho, JH and Gevers, D and Chu, H}, title = {Genetic Factors and the Intestinal Microbiome Guide Development of Microbe-Based Therapies for Inflammatory Bowel Diseases.}, journal = {Gastroenterology}, volume = {156}, number = {8}, pages = {2174-2189}, doi = {10.1053/j.gastro.2019.03.017}, pmid = {30880022}, issn = {1528-0012}, support = {U01 DK062429/DK/NIDDK NIH HHS/United States ; U01 DK062422/DK/NIDDK NIH HHS/United States ; K08 DK109287/DK/NIDDK NIH HHS/United States ; R00 DK110534/DK/NIDDK NIH HHS/United States ; R01 DK106593/DK/NIDDK NIH HHS/United States ; R01 DK092235/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Drugs, Investigational/*administration &amp; dosage/pharmacology ; Gastrointestinal Microbiome/*genetics/*immunology ; Genome, Human ; Humans ; Immunotherapy/*methods ; Inflammatory Bowel Diseases/microbiology/pathology/*therapy ; Mice ; Models, Animal ; *Practice Guidelines as Topic ; Prognosis ; Treatment Outcome ; }, abstract = {The intestinal microbiota is a dynamic community of bacteria, fungi, and viruses that mediates mucosal homeostasis and physiology. Imbalances in the microbiome and aberrant immune responses to gut bacteria can disrupt homeostasis and are associated with inflammatory bowel diseases (IBDs) in humans and colitis in mice. We review genetic variants associated with IBD and their effects on the intestinal microbiome, the immune response, and disease pathogenesis. The intestinal microbiome, which includes microbial antigens, adjuvants, and metabolic products, affects the development and function of the intestinal mucosa, influencing inflammatory responses in the gut. Therefore, strategies to manipulate the microbiome might be used in treatment of IBD. We review microbe-based therapies for IBD and the potential to engineer patients' intestinal microbiota. We discuss how studies of patients with IBD and mouse models have advanced our understanding of the interactions between genetic factors and the gut microbiome, and challenges to the development of microbe-based therapies for IBD.}, }
@article {pmid30877283, year = {2019}, author = {Shaw, LP and Bassam, H and Barnes, CP and Walker, AS and Klein, N and Balloux, F}, title = {Modelling microbiome recovery after antibiotics using a stability landscape framework.}, journal = {The ISME journal}, volume = {13}, number = {7}, pages = {1845-1856}, doi = {10.1038/s41396-019-0392-1}, pmid = {30877283}, issn = {1751-7370}, support = {//Wellcome Trust/United Kingdom ; 209409//Wellcome Trust/United Kingdom ; EP/F500351/1//RCUK | Engineering and Physical Sciences Research Council (EPSRC)/ ; 097319/Z/11/Z//Wellcome Trust (Wellcome)/ ; }, abstract = {Treatment with antibiotics is one of the most extreme perturbations to the human microbiome. Even standard courses of antibiotics dramatically reduce the microbiome's diversity and can cause transitions to dysbiotic states. Conceptually, this is often described as a 'stability landscape': the microbiome sits in a landscape with multiple stable equilibria, and sufficiently strong perturbations can shift the microbiome from its normal equilibrium to another state. However, this picture is only qualitative and has not been incorporated in previous mathematical models of the effects of antibiotics. Here, we outline a simple quantitative model based on the stability landscape concept and demonstrate its success on real data. Our analytical impulse-response model has minimal assumptions with three parameters. We fit this model in a Bayesian framework to data from a previous study of the year-long effects of short courses of four common antibiotics on the gut and oral microbiomes, allowing us to compare parameters between antibiotics and microbiomes, and further validate our model using data from another study looking at the impact of a combination of last-resort antibiotics on the gut microbiome. Using Bayesian model selection we find support for a long-term transition to an alternative microbiome state after courses of certain antibiotics in both the gut and oral microbiomes. Quantitative stability landscape frameworks are an exciting avenue for future microbiome modelling.}, }
@article {pmid30876799, year = {2019}, author = {Douillard, FP and de Vos, WM}, title = {Biotechnology of health-promoting bacteria.}, journal = {Biotechnology advances}, volume = {37}, number = {6}, pages = {107369}, doi = {10.1016/j.biotechadv.2019.03.008}, pmid = {30876799}, issn = {1873-1899}, abstract = {Over the last decade, there has been an increasing scientific and public interest in bacteria that may positively contribute to human gut health and well-being. This interest is reflected by the ever-increasing number of developed functional food products containing health-promoting bacteria and reaching the market place as well as by the growing revenue and profits of notably bacterial supplements worldwide. Traditionally, the origin of probiotic-marketed bacteria was limited to a rather small number of bacterial species that mostly belong to lactic acid bacteria and bifidobacteria. Intensifying research efforts on the human gut microbiome offered novel insights into the role of human gut microbiota in health and disease, while also providing a deep and increasingly comprehensive understanding of the bacterial communities present in this complex ecosystem and their interactions with the gut-liver-brain axis. This resulted in rational and systematic approaches to select novel health-promoting bacteria or to engineer existing bacteria with enhanced probiotic properties. In parallel, the field of gut microbiomics developed into a fertile framework for the identification, isolation and characterization of a phylogenetically diverse array of health-promoting bacterial species, also called next-generation therapeutic bacteria. The present review will address these developments with specific attention for the selection and improvement of a selected number of health-promoting bacterial species and strains that are extensively studied or hold promise for future food or pharma product development.}, }
@article {pmid30871856, year = {2019}, author = {Minot, SS}, title = {De novo Assembly Vastly Expands the Known Microbial Universe.}, journal = {Trends in microbiology}, volume = {27}, number = {5}, pages = {385-386}, doi = {10.1016/j.tim.2019.02.007}, pmid = {30871856}, issn = {1878-4380}, abstract = {The study of the human microbiome relies heavily on the genomes of bacterial isolates that can be grown in culture. A recent study (Pasolli et al. Cell 2019;176:649-662) of stool microbiome samples generated over 150 000 microbial genomes without any culture, vastly expanding our knowledge of the biases in existing reference databases.}, }
@article {pmid30871469, year = {2019}, author = {Perz, AI and Giles, CB and Brown, CA and Porter, H and Roopnarinesingh, X and Wren, JD}, title = {MNEMONIC: MetageNomic Experiment Mining to create an OTU Network of Inhabitant Correlations.}, journal = {BMC bioinformatics}, volume = {20}, number = {Suppl 2}, pages = {96}, doi = {10.1186/s12859-019-2623-x}, pmid = {30871469}, issn = {1471-2105}, support = {P20 GM103636/GM/NIGMS NIH HHS/United States ; P30 AG050911/AG/NIA NIH HHS/United States ; }, mesh = {Humans ; Metagenomics/*methods ; Microbiota/*genetics ; }, abstract = {BACKGROUND: The number of publicly available metagenomic experiments in various environments has been rapidly growing, empowering the potential to identify similar shifts in species abundance between different experiments. This could be a potentially powerful way to interpret new experiments, by identifying common themes and causes behind changes in species abundance.<br><br>RESULTS: We propose a novel framework for comparing microbial shifts between conditions. Using data from one of the largest human metagenome projects to date, the American Gut Project (AGP), we obtain differential abundance vectors for microbes using experimental condition information provided with the AGP metadata, such as patient age, dietary habits, or health status. We show it can be used to identify similar and opposing shifts in microbial species, and infer putative interactions between microbes. Our results show that groups of shifts with similar effects on microbiome can be identified and that similar dietary interventions display similar microbial abundance shifts.<br><br>CONCLUSIONS: Without comparison to prior data, it is difficult for experimentalists to know if their observed changes in species abundance have been observed by others, both in their conditions and in others they would never consider comparable. Yet, this can be a very important contextual factor in interpreting the significance of a shift. We've proposed and tested an algorithmic solution to this problem, which also allows for comparing the metagenomic signature shifts between conditions in the existing body of data.}, }
@article {pmid30870464, year = {2019}, author = {Burcham, ZM and Schmidt, CJ and Pechal, JL and Brooks, CP and Rosch, JW and Benbow, ME and Jordan, HR}, title = {Detection of critical antibiotic resistance genes through routine microbiome surveillance.}, journal = {PloS one}, volume = {14}, number = {3}, pages = {e0213280}, doi = {10.1371/journal.pone.0213280}, pmid = {30870464}, issn = {1932-6203}, abstract = {Population-based public health data on antibiotic resistance gene carriage is poorly surveyed. Research of the human microbiome as an antibiotic resistance reservoir has primarily focused on gut associated microbial communities, but data have shown more widespread microbial colonization across organs than originally believed, with organs previously considered as sterile being colonized. Our study demonstrates the utility of postmortem microbiome sampling during routine autopsy as a method to survey antibiotic resistance carriage in a general population. Postmortem microbial sampling detected pathogens of public health concern including genes for multidrug efflux pumps, carbapenem, methicillin, vancomycin, and polymixin resistances. Results suggest that postmortem assessments of host-associated microbial communities are useful in acquiring community specific data while reducing selective-participant biases.}, }
@article {pmid30867232, year = {2019}, author = {Elzinga, J and van der Oost, J and de Vos, WM and Smidt, H}, title = {The Use of Defined Microbial Communities To Model Host-Microbe Interactions in the Human Gut.}, journal = {Microbiology and molecular biology reviews : MMBR}, volume = {83}, number = {2}, pages = {}, doi = {10.1128/MMBR.00054-18}, pmid = {30867232}, issn = {1098-5557}, mesh = {Animals ; Bacteria/classification ; Cell Culture Techniques ; *Gastrointestinal Microbiome ; Gastrointestinal Tract/*microbiology ; Genomics/methods ; *Host Microbial Interactions ; Humans ; Mice ; *Microbiota ; *Models, Animal ; }, abstract = {The human intestinal ecosystem is characterized by a complex interplay between different microorganisms and the host. The high variation within the human population further complicates the quest toward an adequate understanding of this complex system that is so relevant to human health and well-being. To study host-microbe interactions, defined synthetic bacterial communities have been introduced in gnotobiotic animals or in sophisticated in vitro cell models. This review reinforces that our limited understanding has often hampered the appropriate design of defined communities that represent the human gut microbiota. On top of this, some communities have been applied to in vivo models that differ appreciably from the human host. In this review, the advantages and disadvantages of using defined microbial communities are outlined, and suggestions for future improvement of host-microbe interaction models are provided. With respect to the host, technological advances, such as the development of a gut-on-a-chip system and intestinal organoids, may contribute to more-accurate in vitro models of the human host. With respect to the microbiota, due to the increasing availability of representative cultured isolates and their genomic sequences, our understanding and controllability of the human gut &quot;core microbiota&quot; are likely to increase. Taken together, these advancements could further unravel the molecular mechanisms underlying the human gut microbiota superorganism. Such a gain of insight would provide a solid basis for the improvement of pre-, pro-, and synbiotics as well as the development of new therapeutic microbes.}, }
@article {pmid30863868, year = {2019}, author = {Plantinga, AM and Chen, J and Jenq, RR and Wu, MC}, title = {pldist: ecological dissimilarities for paired and longitudinal microbiome association analysis.}, journal = {Bioinformatics (Oxford, England)}, volume = {}, number = {}, pages = {}, doi = {10.1093/bioinformatics/btz120}, pmid = {30863868}, issn = {1367-4811}, support = {S10 OD020069/OD/NIH HHS/United States ; }, abstract = {MOTIVATION: The human microbiome is notoriously variable across individuals, with a wide range of 'healthy' microbiomes. Paired and longitudinal studies of the microbiome have become increasingly popular as a way to reduce unmeasured confounding and to increase statistical power by reducing large inter-subject variability. Statistical methods for analyzing such datasets are scarce.<br><br>RESULTS: We introduce a paired UniFrac dissimilarity that summarizes within-individual (or within-pair) shifts in microbiome composition and then compares these compositional shifts across individuals (or pairs). This dissimilarity depends on a novel transformation of relative abundances, which we then extend to more than two time points and incorporate into several phylogenetic and non-phylogenetic dissimilarities. The data transformation and resulting dissimilarities may be used in a wide variety of downstream analyses, including ordination analysis and distance-based hypothesis testing. Simulations demonstrate that tests based on these dissimilarities retain appropriate type 1 error and high power. We apply the method in two real datasets.<br><br>The R package pldist is available on GitHub at https://github.com/aplantin/pldist.<br><br>SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.}, }
@article {pmid30843443, year = {2019}, author = {Salvucci, E}, title = {The human-microbiome superorganism and its modulation to restore health.}, journal = {International journal of food sciences and nutrition}, volume = {70}, number = {7}, pages = {781-795}, doi = {10.1080/09637486.2019.1580682}, pmid = {30843443}, issn = {1465-3478}, abstract = {Microbiome is the community of microorganism that co-live with a host. The human being is the result of the integration of its genome and the coexistence with millions of microorganisms throughout its evolutionary history. Human-microbiome association can be considered a step of integration in evolution, constituting a superorganism. Many emergent diseases are related to the loss of part of this microbiome and its restoration can be achieved by different strategies. Gut microbiome imbalance is particularly associated with numerous inflammatory, immune and nervous system-related diseases by a communication pathway called microbiome-brain axis. Modulation of microbiome by administering prebiotics, like arabinoxylans, and synbiotics is a plausible treatment for dysbiosis, the regulation of neurotransmitters and alleviation of neurological manifestations.}, }
@article {pmid30835913, year = {2019}, author = {Rego, S and Dagan-Rosenfeld, O and Bivona, SA and Snyder, MP and Ormond, KE}, title = {Much ado about nothing: A qualitative study of the experiences of an average-risk population receiving results of exome sequencing.}, journal = {Journal of genetic counseling}, volume = {28}, number = {2}, pages = {428-437}, doi = {10.1002/jgc4.1096}, pmid = {30835913}, issn = {1573-3599}, support = {U54 DE023789/DE/NIDCR NIH HHS/United States ; 1U54DE02378901//NIH Common Fund Human Microbiome Project (HMP)/ ; 1-14-TS-28//American Diabetes Association/ ; 1-11-CT-35//American Diabetes Association/ ; }, abstract = {The increasing availability of exome sequencing to the general (&quot;healthy&quot;) population raises questions about the implications of genomic testing for individuals without suspected Mendelian diseases. Little is known about this population's motivations for undergoing exome sequencing, their expectations, reactions, and perceptions of utility. In order to address these questions, we conducted in-depth semi-structured interviews with 12 participants recruited from a longitudinal multi-omics profiling study that included exome sequencing. Participants were interviewed after receiving exome results, which included Mendelian disease-associated pathogenic and likely pathogenic variants, pharmacogenetic variants, and risk assessments for multifactorial diseases such as type 2 diabetes. The primary motivation driving participation in exome sequencing was personal curiosity. While they reported feeling validation and relief, participants were frequently underwhelmed by the results and described having expected more from exome sequencing. All participants reported discussing the results with at least some family, friends, and healthcare providers. Participants' recollection of the results returned to them was sometimes incorrect or incomplete, in many cases aligning with their perceptions of their health risks when entering the study. These results underscore the need for different genetic counseling approaches for generally healthy patients undergoing exome sequencing, in particular the need to provide anticipatory guidance to moderate participants' expectations. They also provide a preview of potential challenges clinicians may face as genomic sequencing continues to scale-up in the general population despite a lack of full understanding of its impact.}, }
@article {pmid30835837, year = {2019}, author = {Haahtela, T}, title = {A biodiversity hypothesis.}, journal = {Allergy}, volume = {74}, number = {8}, pages = {1445-1456}, doi = {10.1111/all.13763}, pmid = {30835837}, issn = {1398-9995}, abstract = {Biodiversity hypothesis states that contact with natural environments enriches the human microbiome, promotes immune balance and protects from allergy and inflammatory disorders. We are protected by two nested layers of biodiversity, microbiota of the outer layer (soil, natural waters, plants, animals) and inner layer (gut, skin, airways). The latter inhabits our body and is colonized from the outer layer. Explosion of human populations along with cultural evolution is profoundly changing our environment and lifestyle. Adaptive immunoregulatory circuits and dynamic homeostasis are at stake in the newly emerged urban surroundings. In allergy, and chronic inflammatory disorders in general, exploring the determinants of immunotolerance is the key for prevention and more effective treatment. Loss of immunoprotective factors, derived from nature, is a new kind of health risk poorly acknowledged until recently. The paradigm change has been implemented in the Finnish allergy programme (2008-2018), which emphasized tolerance instead of avoidance. The first results are promising, as allergy burden has started to reduce. The rapidly urbanizing world is facing serious biodiversity loss with global warming, which are interconnected. Biodiversity hypothesis of health and disease has societal impact, for example, on city planning, food and energy production and nature conservation. It has also a message for individuals for health and well-being: take nature close, to touch, eat, breathe, experience and enjoy. Biodiverse natural environments are dependent on planetary health, which should be a priority also among health professionals.}, }
@article {pmid30835680, year = {2019}, author = {Wallace, DJ and Sayre, NL and Patterson, TT and Nicholson, SE and Hilton, D and Grandhi, R}, title = {Spinal cord injury and the human microbiome: beyond the brain-gut axis.}, journal = {Neurosurgical focus}, volume = {46}, number = {3}, pages = {E11}, doi = {10.3171/2018.12.FOCUS18206}, pmid = {30835680}, issn = {1092-0684}, abstract = {In addition to standard management for the treatment of the acute phase of spinal cord injury (SCI), implementation of novel neuroprotective interventions offers the potential for significant reductions in morbidity and long-term health costs. A better understanding of the systemic changes after SCI could provide insight into mechanisms that lead to secondary injury. An emerging area of research involves the complex interplay of the gut microbiome and the CNS, i.e., a brain-gut axis, or perhaps more appropriately, a CNS-gut axis. This review summarizes the relevant literature relating to the gut microbiome and SCI. Experimental models in stroke and traumatic brain injury demonstrate the bidirectional communication of the CNS to the gut with postinjury dysbiosis, gastrointestinal-associated lymphoid tissue-mediated neuroinflammatory responses, and bacterial-metabolite neurotransmission. Similar findings are being elucidated in SCI as well. Experimental interventions in these areas have shown promise in improving functional outcomes in animal models. This commensal relationship between the human body and its microbiome, particularly the gut microbiome, represents an exciting frontier in experimental medicine.}, }
@article {pmid30832730, year = {2019}, author = {Meyer, F and Bremges, A and Belmann, P and Janssen, S and McHardy, AC and Koslicki, D}, title = {Assessing taxonomic metagenome profilers with OPAL.}, journal = {Genome biology}, volume = {20}, number = {1}, pages = {51}, doi = {10.1186/s13059-019-1646-y}, pmid = {30832730}, issn = {1474-760X}, mesh = {Classification/methods ; Humans ; Metagenomics/methods/*standards ; *Software ; }, abstract = {The explosive growth in taxonomic metagenome profiling methods over the past years has created a need for systematic comparisons using relevant performance criteria. The Open-community Profiling Assessment tooL (OPAL) implements commonly used performance metrics, including those of the first challenge of the initiative for the Critical Assessment of Metagenome Interpretation (CAMI), together with convenient visualizations. In addition, we perform in-depth performance comparisons with seven profilers on datasets of CAMI and the Human Microbiome Project. OPAL is freely available at https://github.com/CAMI-challenge/OPAL .}, }
@article {pmid30830433, year = {2019}, author = {Piersigilli, F and Lam, TT and Vernocchi, P and Quagliariello, A and Putignani, L and Aghai, ZH and Bhandari, V}, title = {Identification of new biomarkers of bronchopulmonary dysplasia using metabolomics.}, journal = {Metabolomics : Official journal of the Metabolomic Society}, volume = {15}, number = {2}, pages = {20}, doi = {10.1007/s11306-019-1482-9}, pmid = {30830433}, issn = {1573-3890}, abstract = {OBJECTIVE: To identify new biomarkers of bronchopulmonary dysplasia (BPD) in preterm neonates.<br><br>STUDY DESIGN: Metabolomic study of prospectively collected tracheal aspirate (TA) samples from preterm neonates admitted in 2 neonatal intensive care units measured by a mass spectroscopy-based assay and analysed using partial least squares-discriminant analysis.<br><br>RESULTS: We evaluated 160 TA samples from 68 neonates, 44 with BPD and 24 without BPD in the first week of life. A cluster of 53 metabolites was identified as characteristic of BPD, with 18 select metabolites being highly significant in the separation of BPD versus No BPD. To control for the gestational age (GA) differences, we did a sub-group analyses, and noted that the amino acids histidine, glutamic acid, citrulline, glycine and isoleucine levels were higher in neonates with BPD. In addition, acylcarnitines C16-OH and C18:1-OH were also higher in neonates who developed BPD, but especially in the most preterm infants (neonates with GA < 27 weeks).<br><br>CONCLUSION: Metabolomics is a promising approach to identify novel specific biomarkers for BPD.}, }
@article {pmid30828318, year = {2019}, author = {Reid, G}, title = {Disentangling What We Know About Microbes and Mental Health.}, journal = {Frontiers in endocrinology}, volume = {10}, number = {}, pages = {81}, doi = {10.3389/fendo.2019.00081}, pmid = {30828318}, issn = {1664-2392}, abstract = {Much has been written in recent years about the gut-brain axis. Exciting pilot studies suggest probiotic applications to the gut can reduce anxiety and depression via the vagus nerve. But not to diminish such findings, much still needs to be considered, including the fact that the vagus nerve links to many other body sites that also host a microbiome. Questions remain that touch the core of being human: (i) Do our microbes influence happiness and to what extent? (ii) What components of the gut microbiota and their function, including as it relates to mental health, are critical and how do they differ between agile, fit hunter gatherers and obese westerners or Danes described as the happiest people on the planet? (iii) What role do environmental pollutants play in this microbes-host ecosystem? While approaching life from a reductionist perspective has a long history in science, we need to try to interrogate these health and disease issues from a wider perspective. For verification of a link between the gut microbiota and brain, and to test new therapies, human studies are needed, and are long overdue.}, }
@article {pmid30814984, year = {2019}, author = {Song, Z and Wang, X and Zhou, X and Jiang, S and Li, Y and Ahmad, O and Qi, L and Li, P and Li, J}, title = {Taxonomic Distribution of FosB in Human-Microbiota and Activity Comparison of Fosfomycin Resistance.}, journal = {Frontiers in microbiology}, volume = {10}, number = {}, pages = {200}, doi = {10.3389/fmicb.2019.00200}, pmid = {30814984}, issn = {1664-302X}, abstract = {FosB, a Mg2+ dependent thioltransferase, confers antibiotic resistance to fosfomycin through enzymatic drug inactivation. Among all antibiotic resistant proteins in the Antibiotic Resistance Genes Database and the Comprehensive Antibiotic Resistance Database, FosB is within 5% of the most number of ARPs identified in Human Microbiome Project reference database but mainly distributed in limited genera, i.e., 122 of total 133 FosB homologues are found from Bacillus and Staphylococcus. Furthermore, these FosB sequences could be divided into three clusters based on their phylogenetic relationship, i.e., two groups of FosB were mainly from Bacillus, and another was mainly from Staphylococcus. Finally, we confirmed that FosB from the group of Staphylococcus presented the highest resistance ability to fosfomycin by in silico and in vitro comparisons. In summary, this study elaborates the specific taxonomic characteristics and resistant abilities of FosB in human microbiota, which might help in developing more promising fosfomycin-like antibiotics.}, }
@article {pmid30811000, year = {2019}, author = {Shan, Y and Wu, W and Fan, W and Haahtela, T and Zhang, G}, title = {House dust microbiome and human health risks.}, journal = {International microbiology : the official journal of the Spanish Society for Microbiology}, volume = {22}, number = {3}, pages = {297-304}, doi = {10.1007/s10123-019-00057-5}, pmid = {30811000}, issn = {1618-1905}, abstract = {People spend a lot of time indoors and the indoor microbiome is a major part of the environment that we are exposed to. However, awareness of the exposure to the indoor microbiome and its health effects remains poor. Outdoor environment (soil and air), indoor sources (ventilation, dampness and building materials), human occupants, and pets compose the indoor microbial community. It has been estimated that up to 500-1000 different species can be present in house dust. House dust is a major source and reservoir of indoor microbiome, which influences human microbiome and determines health and disease. Herein, we review the origins and the components of the fungal and bacterial communities in house dust and their possible effect on human health, in particular on allergic disorders, intestinal microbiome, and immune responses. We expect to lay a solid foundation for the further study on the mechanisms of how the house dust microbes interact with the host microbiome and the human immune system.}, }
@article {pmid30810508, year = {2019}, author = {Falony, G and Vandeputte, D and Caenepeel, C and Vieira-Silva, S and Daryoush, T and Vermeire, S and Raes, J}, title = {The human microbiome in health and disease: hype or hope.}, journal = {Acta clinica Belgica}, volume = {74}, number = {2}, pages = {53-64}, doi = {10.1080/17843286.2019.1583782}, pmid = {30810508}, issn = {2295-3337}, mesh = {Colon/microbiology ; Disease ; Fecal Microbiota Transplantation ; Feces/microbiology ; *Gastrointestinal Microbiome ; Humans ; }, abstract = {OBJECTIVES: The prognostic, diagnostic, and therapeutic potential of the human gut microbiota is widely recognised. However, translation of microbiome findings to clinical practice is challenging. Here, we discuss current knowledge and applications in the field.<br><br>METHODS: We revisit some recent advances in the field of faecal microbiome analyses with a focus on covariate analyses and ecological interpretation.<br><br>RESULTS: Population-level characterization of gut microbiota variation among healthy volunteers has allowed identifying microbiome covariates required for clinical studies. Currently, microbiome research is moving from relative to quantitative approaches that will shed a new light on microbiota-host interactions in health and disease.<br><br>CONCLUSIONS: Covariate characterization and technical advances increase reproducibility of microbiome research. Targeted in vitro/in vivo intervention studies will accelerate clinical implementation of microbiota findings.}, }
@article {pmid30808411, year = {2019}, author = {, }, title = {A review of 10 years of human microbiome research activities at the US National Institutes of Health, Fiscal Years 2007-2016.}, journal = {Microbiome}, volume = {7}, number = {1}, pages = {31}, doi = {10.1186/s40168-019-0620-y}, pmid = {30808411}, issn = {2049-2618}, mesh = {Biomedical Research/*economics/*organization &amp; administration ; Humans ; Metagenomics/economics/organization &amp; administration ; Microbiota ; National Institutes of Health (U.S.) ; United States ; }, abstract = {The National Institutes of Health (NIH) is the primary federal government agency for biomedical research in the USA. NIH provides extensive support for human microbiome research with 21 of 27 NIH Institutes and Centers (ICs) currently funding this area through their extramural research programs. This analysis of the NIH extramural portfolio in human microbiome research briefly reviews the early history of this field at NIH, summarizes the program objectives and the resources developed in the recently completed 10-year (fiscal years 2007-2016) $215 M Human Microbiome Project (HMP) program, evaluates the scope and range of the $728 M NIH investment in extramural human microbiome research activities outside of the HMP over fiscal years 2012-2016, and highlights some specific areas of research which emerged from this investment. This analysis closes with a few comments on the technical needs and knowledge gaps which remain for this field to be able to advance over the next decade and for the outcomes of this research to be able to progress to microbiome-based interventions for treating disease and supporting health.}, }
@article {pmid30808401, year = {2019}, author = {, }, title = {2017 NIH-wide workshop report on &quot;The Human Microbiome: Emerging Themes at the Horizon of the 21st Century&quot;.}, journal = {Microbiome}, volume = {7}, number = {1}, pages = {32}, doi = {10.1186/s40168-019-0627-4}, pmid = {30808401}, issn = {2049-2618}, support = {U54 HD080784/HD/NICHD NIH HHS/United States ; U54 DK102557/DK/NIDDK NIH HHS/United States ; R24 DK110499/DK/NIDDK NIH HHS/United States ; U54 DE023789/DE/NIDCR NIH HHS/United States ; }, mesh = {Humans ; Internet ; *Microbiota ; National Institutes of Health (U.S.) ; United States ; }, abstract = {The National Institutes of Health (NIH) organized a three-day human microbiome research workshop, August 16-18, 2017, to highlight the accomplishments of the 10-year Human Microbiome Project program, the outcomes of the investments made by the 21 NIH Institutes and Centers which now fund this area, and the technical challenges and knowledge gaps which will need to be addressed in order for this field to advance over the next 10 years. This report summarizes the key points in the talks, round table discussions, and Joint Agency Panel from this workshop.}, }
@article {pmid30804923, year = {2018}, author = {Ma, Z and Li, L}, title = {Semen Microbiome Biogeography: An Analysis Based on a Chinese Population Study.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {3333}, doi = {10.3389/fmicb.2018.03333}, pmid = {30804923}, issn = {1664-302X}, abstract = {Investigating inter-subject heterogeneity (or spatial distribution) of human semen microbiome diversity is of important significance. Theoretically, the spatial distribution of biodiversity constitutes the core of microbiome biogeography. Practically, the inter-subject heterogeneity is crucial for understanding the normal (healthy) flora of semen microbiotas as well as their possible changes associated with abnormal fertility. In this article, we analyze the scaling (changes) of semen microbiome diversity across individuals with DAR (diversity-area relationship) analysis, a recent extension to classic SAR (species-area relationship) law in biogeography and ecology. Specifically, the unit of &quot;area&quot; is individual subject, and the microbial diversity in seminal fluid of an individual (area) is assessed via metagenomic DNA sequencing technique and measured in the Hill numbers. The DAR models were then fitted to the accrued diversity across different number of individuals (area size). We further tested the difference in DAR parameters among the healthy, subnormal, and abnormal microbiome samples in terms of their fertility status based on a cross-sectional study of a Chinese cohort. Given that no statistically significant differences in the DAR parameters were detected among the three groups, we built unified DAR models for semen microbiome by combining the healthy, subnormal, and abnormal groups. The model parameters were used to (i) estimate the microbiome diversity scaling in a population (cohort), and construct the so-termed DAR profile; (ii) predict/construct the maximal accrual diversity (MAD) profile in a population; (iii) estimate the pair-wise diversity overlap (PDO) between two individuals and construct the PDO profile; (iv) assess the ratio of individual diversity to population (RIP) accrual diversity. The last item (RIP) is a new concept we propose in this study, which is essentially a ratio of local diversity to regional or global diversity (LRD/LGD), applicable to general biodiversity investigation beyond human microbiome.}, }
@article {pmid30801627, year = {2019}, author = {McSkimming, DI and Banack, HR and Genco, R and Wactawski-Wende, J and LaMonte, MJ}, title = {RE: &quot;QUANTIFICATION OF HUMAN MICROBIOME STABILITY OVER 6 MONTHS: IMPLICATIONS FOR EPIDEMIOLOGIC STUDIES&quot;.}, journal = {American journal of epidemiology}, volume = {188}, number = {4}, pages = {807-808}, doi = {10.1093/aje/kwz021}, pmid = {30801627}, issn = {1476-6256}, }
@article {pmid30799264, year = {2019}, author = {De Filippis, F and Pasolli, E and Tett, A and Tarallo, S and Naccarati, A and De Angelis, M and Neviani, E and Cocolin, L and Gobbetti, M and Segata, N and Ercolini, D}, title = {Distinct Genetic and Functional Traits of Human Intestinal Prevotella copri Strains Are Associated with Different Habitual Diets.}, journal = {Cell host &amp; microbe}, volume = {25}, number = {3}, pages = {444-453.e3}, doi = {10.1016/j.chom.2019.01.004}, pmid = {30799264}, issn = {1934-6069}, abstract = {The role of intestinal Prevotella species in human health is controversial, with both positive and negative associations. Strain-level diversity may contribute to discrepancies in genus and species associations with health and disease. We dissected the gut metagenomes of Italians with varying dietary habits, investigating the presence of distinct Prevotella copri strains. Fiber-rich diets were linked to P. copri types with enhanced potential for carbohydrate catabolism. P. copri strains associated with an omnivore diet had a higher prevalence of the leuB gene-involved in branched-chain amino acid biosynthesis-a risk factor for glucose intolerance and type 2 diabetes. These P. copri pangenomes were compared to existing cohorts, providing evidence of distinct gene repertoires characterizing different P. copri populations, with drug metabolism and complex carbohydrate degradation significantly associated with Western and non-Western individuals, respectively. Strain-level P. copri diversity in gut microbiomes is affected by diet and should be considered when examining host-microbe associations.}, }
@article {pmid30799003, year = {2019}, author = {Rogers, GB and Ward, J and Brown, A and Wesselingh, SL}, title = {Inclusivity and equity in human microbiome research.}, journal = {Lancet (London, England)}, volume = {393}, number = {10173}, pages = {728-729}, doi = {10.1016/S0140-6736(18)33204-5}, pmid = {30799003}, issn = {1474-547X}, mesh = {Biomedical Research/*standards ; Continental Population Groups ; Health Status Disparities ; Humans ; Microbiota/*genetics ; Oceanic Ancestry Group ; }, }
@article {pmid30777586, year = {2019}, author = {Araos, R and D'Agata, EMC}, title = {The human microbiota and infection prevention.}, journal = {Infection control and hospital epidemiology}, volume = {40}, number = {5}, pages = {585-589}, doi = {10.1017/ice.2019.28}, pmid = {30777586}, issn = {1559-6834}, abstract = {The human microbiome participates in numerous aspects of human physiology and disease states. Recently, studies have begun to explore the role of the microbiome in colonization, infection and transmission of pathogens. This review provides a summary of the methodological principles used in microbiome studies and the published evidence of the impact of microbiome dysbiosis in infection prevention.}, }
@article {pmid30772579, year = {2019}, author = {Li, H and Zhou, XY and Yang, XR and Zhu, YG and Hong, YW and Su, JQ}, title = {Spatial and seasonal variation of the airborne microbiome in a rapidly developing city of China.}, journal = {The Science of the total environment}, volume = {665}, number = {}, pages = {61-68}, doi = {10.1016/j.scitotenv.2019.01.367}, pmid = {30772579}, issn = {1879-1026}, mesh = {*Air Microbiology ; Air Pollutants/*analysis ; Air Pollution/*statistics &amp; numerical data ; Bacteria ; China ; Cities ; Climate ; *Environmental Monitoring ; Firmicutes ; *Microbiota ; Proteobacteria ; RNA, Ribosomal, 16S ; Seasons ; Urbanization ; }, abstract = {Exposure to airborne microbes (AM) can affect the human microbiome and has various consequences for human health. Investigating the profiles of AM and the potential bacterial pathogens within, along with the factors influencing their community, is pivotal for understanding the impact of AM on human health. In this study, we collected AM during spring and summer from 11 sites with various levels of urbanization in the city of Xiamen, China. Bacterial community compositions of the AM were determined based on 16S rRNA gene amplicon sequencing. Firmicutes and Proteobacteria were the predominating phyla in the airborne bacterial communities, and a higher (P < 0.05) diversity of AM was found during the summer as compared to the spring. Significant differences in the community structure of the AM and the potential bacterial pathogens within airborne microbes were observed among the seasons and the sites with different levels of urbanization. Increases and/or decreases in the abundance of Bacillus and Acinetobacter could explain a major part of the variations in the AM community compositions. The proportion of potential bacterial pathogens during the summer was significantly higher (P < 0.01) than in the spring, and the relative abundance of several bacterial pathogens (i.e. Burkholderia multivoran, Enterococcus faecium and Streptococcus thermophilus) related to human diseases (39.8% of total pathogens on average) increased with increasing urbanization levels, suggesting that urbanization can increase the AM-associated human health risk.}, }
@article {pmid30767956, year = {2019}, author = {Bai, J and Jhaney, I and Daniel, G and Watkins Bruner, D}, title = {Pilot Study of Vaginal Microbiome Using QIIME 2™ in Women With Gynecologic Cancer Before and After Radiation Therapy.}, journal = {Oncology nursing forum}, volume = {46}, number = {2}, pages = {E48-E59}, doi = {10.1188/19.ONF.E48-E59}, pmid = {30767956}, issn = {1538-0688}, mesh = {Adult ; Aged ; Female ; Genital Neoplasms, Female/*microbiology/*radiotherapy ; Georgia ; Humans ; Microbiota/*genetics/*radiation effects ; Middle Aged ; Pilot Projects ; RNA, Ribosomal, 16S/*analysis ; Vagina/*microbiology ; }, abstract = {OBJECTIVES: To characterize the vaginal microbiome using QIIME 2™ (Quantitative Insights Into Microbial Ecology 2) in women with gynecologic cancer.<br><br>SAMPLE &amp;AMP; SETTING: 19 women with gynecologic cancer before and after radiation therapy at a comprehensive cancer center in Atlanta, Georgia.<br><br>METHODS &amp;AMP; VARIABLES: This pilot study analyzed vaginal microbiome communities using a microbiome analysis pipeline, beginning with 16S rRNA gene sequencing and processing through use of a bioinformatics pipeline to downstream microbial statistical analysis.<br><br>RESULTS: The findings showed the methods to be robust, and most women with gynecologic cancer showed depletion of Lactobacillus. Compared to those pre-radiation therapy, women post-radiation therapy showed higher abundances of Mobiluncus, Atopobium, and Prevotella but lower abundances of Lactobacillus, Gardnerella, and Peptostreptococcus, which are associated with bacterial vaginosis.<br><br>IMPLICATIONS FOR NURSING: This study presents the fundamentals of human microbiome data collection and analysis methods to inform nursing science. Assessing the vaginal microbiome provides a potential pathway to develop interventions to ameliorate dysbiosis of the vaginal microbiome.}, }
@article {pmid30764863, year = {2019}, author = {Luo, Z and Li, M and Wu, Y and Meng, Z and Martin, L and Zhang, L and Ogunrinde, E and Zhou, Z and Qin, S and Wan, Z and Westerink, MAJ and Warth, S and Liu, H and Jin, P and Stroncek, D and Li, QZ and Wang, E and Wu, X and Heath, SL and Li, Z and Alekseyenko, AV and Jiang, W}, title = {Systemic translocation of Staphylococcus drives autoantibody production in HIV disease.}, journal = {Microbiome}, volume = {7}, number = {1}, pages = {25}, doi = {10.1186/s40168-019-0646-1}, pmid = {30764863}, issn = {2049-2618}, support = {I01 CX001211/CX/CSRD VA/United States ; R01 CA213290/CA/NCI NIH HHS/United States ; P01 CA186866/CA/NCI NIH HHS/United States ; R01 AI114380/AI/NIAID NIH HHS/United States ; P30 AI027767/AI/NIAID NIH HHS/United States ; UL1 TR001450/TR/NCATS NIH HHS/United States ; R01 AG045973/AG/NIA NIH HHS/United States ; R01 AI128864/AI/NIAID NIH HHS/United States ; R01 AI091526/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Autoantibodies/blood/*metabolism ; *Bacterial Translocation ; DNA, Bacterial/blood ; DNA, Ribosomal/blood ; Disease Models, Animal ; Germinal Center/immunology ; HIV Infections/*immunology ; Hep G2 Cells ; Humans ; Immunity, Innate ; Influenza Vaccines/*immunology ; Influenza, Human/prevention &amp; control ; Lymphocyte Activation ; Male ; Mice ; Single-Cell Analysis ; Staphylococcus/genetics/immunology/*physiology ; Up-Regulation ; }, abstract = {BACKGROUND: Increased autoreactive antibodies have been reported in HIV disease; however, the mechanism accounting for autoantibody induction in HIV remains unknown.<br><br>RESULTS: Herein, we show that seasonal influenza vaccination induces autoantibody production (e.g., IgG anti-nuclear antibody (ANA) and anti-double-stranded DNA antibody (anti-dsDNA)) in some viral-suppressed antiretroviral therapy (ART)-treated HIV+ subjects, but not in healthy controls. These autoantibodies were not derived from antigen-specific B cells but from activated &quot;bystander&quot; B cells analyzed by single-cell assay and by study of purified polyclonal ANAs from plasma. To explore the mechanism of autoantibody generation in HIV+ subjects, plasma level of microbial products, gene expression profile of B cells, and B cell receptor (BCR) repertoires were analyzed. We found that autoantibody production was associated with increased plasma level of microbial translocation; the patients with high autoantibodies had skewed B cell repertoires and upregulation of genes related to innate immune activation in response to microbial translocation. By analyzing circulating microbial 16S rDNA in plasma, the relative abundance of Staphylococcus was found to be associated with autoantibody production in HIV+ subjects. Finally, we found that injection of heat-killed Staphylococcus aureus promoted germinal center B cell responses and autoantibody production in mice, consistent with the notion that autoantibody production in HIV+ patients is triggered by microbial products.<br><br>CONCLUSIONS: Our results showed that translocation of Staphylococcus can promote B cell activation through enhancing germinal center response and induces autoantibody production. It uncovers a potential mechanism linking microbial translocation and autoimmunity in HIV+ disease and provides a strong rationale for targeting Staphylococcus to prevent autoantibody production.}, }
@article {pmid30763534, year = {2019}, author = {Shkoporov, AN and Hill, C}, title = {Bacteriophages of the Human Gut: The &quot;Known Unknown&quot; of the Microbiome.}, journal = {Cell host &amp; microbe}, volume = {25}, number = {2}, pages = {195-209}, doi = {10.1016/j.chom.2019.01.017}, pmid = {30763534}, issn = {1934-6069}, abstract = {The human gut microbiome is a dense and taxonomically diverse consortium of microorganisms. While the bacterial components of the microbiome have received considerable attention, comparatively little is known about the composition and physiological significance of human gut-associated bacteriophage populations (phageome). By extrapolating our knowledge of phage-host interactions from other environments, one could expect that >1012 viruses reside in the human gut, and we can predict that they play important roles in regulating the complex microbial networks operating in this habitat. Before delving into their function, we need to first overcome the challenges associated with studying and characterizing the phageome. In this Review, we summarize the available methods and main findings regarding taxonomic composition, community structure, and population dynamics in the human gut phageome. We also discuss the main challenges in the field and identify promising avenues for future research.}, }
@article {pmid30759766, year = {2019}, author = {Reddel, S and Putignani, L and Del Chierico, F}, title = {The Impact of Low-FODMAPs, Gluten-Free, and Ketogenic Diets on Gut Microbiota Modulation in Pathological Conditions.}, journal = {Nutrients}, volume = {11}, number = {2}, pages = {}, doi = {10.3390/nu11020373}, pmid = {30759766}, issn = {2072-6643}, mesh = {*Diet, Gluten-Free ; *Diet, Ketogenic ; *Dietary Carbohydrates ; Gastrointestinal Diseases/*diet therapy/microbiology ; *Gastrointestinal Microbiome ; Humans ; }, abstract = {The gut microbiota performs several essential protective, structural, and metabolic functions for host health. The maintenance of a beneficial microbiota requires a homeostatic equilibrium within microbial communities, and between the microorganisms and the host. The gut microbiota composition may be affected by external factors, among them diet habits may be considered most important. In some pathological conditions such as irritable bowel syndrome (IBS), celiac disease (CD), or neurological disorders (ND), specific dietary regimens as low-fermentable, oligo-, di-, mono-saccharides and polyols (FODMAPs), ketogenic (KD), and gluten-free (GFD) diets are considered therapeutic. These kinds of diets are characterized by a reduction or exclusion of a specific nutrient from the entire dietary pattern. Despite these alimentary regimens showing beneficial effects on disease symptoms, they can affect microbiota composition, especially if they are protracted for a long time. To date, only a few studies have reported the effects of these diets on gut microbiota. In this review, we discuss the effects of low-FODMAPs, KD, and GFD on gut microbiota modulation in pathological conditions, advancing the possibility of depicting a balanced diet and developing personalized dietary intervention protocols.}, }
@article {pmid30744677, year = {2019}, author = {Blakeley-Ruiz, JA and Erickson, AR and Cantarel, BL and Xiong, W and Adams, R and Jansson, JK and Fraser, CM and Hettich, RL}, title = {Metaproteomics reveals persistent and phylum-redundant metabolic functional stability in adult human gut microbiomes of Crohn's remission patients despite temporal variations in microbial taxa, genomes, and proteomes.}, journal = {Microbiome}, volume = {7}, number = {1}, pages = {18}, doi = {10.1186/s40168-019-0631-8}, pmid = {30744677}, issn = {2049-2618}, support = {UH2 DK083991/DK/NIDDK NIH HHS/United States ; }, mesh = {Acetylglucosamine/analysis ; Adult ; Bacteria/genetics/*metabolism ; Crohn Disease/*microbiology/surgery ; Cytidine Monophosphate N-Acetylneuraminic Acid/analysis ; Fatty Acids, Volatile/analysis ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/genetics/*physiology ; Humans ; Male ; Middle Aged ; Proteome/*metabolism ; Proteomics ; RNA, Ribosomal, 16S/genetics ; }, abstract = {BACKGROUND: The gut microbiome plays a fundamental role in the human host's overall health by contributing key biological functions such as expanded metabolism and pathogen defense/immune control. In a healthy individual, the gut microbiome co-exists within the human host in a symbiotic, non-inflammatory relationship that enables mutual benefits, such as microbial degradation of indigestible food products into small molecules that the host can utilize, and enhanced pathogen defense. In abnormal conditions, such as Crohn's disease, this favorable metabolic relationship breaks down and a variety of undesirable activities result, including chronic inflammation and other health-related issues. It has been difficult, however, to elucidate the overall functional characteristics of this relationship because the microbiota can vary substantially in composition for healthy humans and possibly even more in individuals with gut disease conditions such as Crohn's disease. Overall, this suggests that microbial membership composition may not be the best way to characterize a phenotype. Alternatively, it seems to be more informative to examine and characterize the functional composition of a gut microbiome. Towards that end, this study examines 25 metaproteomes measured in several Crohn's disease patients' post-resection surgery across the course of 1 year, in order to examine persistence of microbial taxa, genes, proteins, and metabolic functional distributions across time in individuals whose microbiome might be more variable due to the gut disease condition.<br><br>RESULTS: The measured metaproteomes were highly personalized, with all the temporally-related metaproteomes clustering most closely by individual. In general, the metaproteomes were remarkably distinct between individuals and to a lesser extent within individuals. This prompted a need to characterize the metaproteome at a higher functional level, which was achieved by annotating identified protein groups with KEGG orthologous groups to infer metabolic modules. At this level, similar and redundant metabolic functions across multiple phyla were observed across time and between individuals. Tracking through these various metabolic modules revealed a clear path from carbohydrate, lipid, and amino acid degradation to central metabolism and finally the production of fermentation products.<br><br>CONCLUSIONS: The human gut metaproteome can vary quite substantially across time and individuals. However, despite substantial intra-individual variation in the metaproteomes, there is a clear persistence of conserved metabolic functions across time and individuals. Additionally, the persistence of these core functions is redundant across multiple phyla but is not always observable in the same sample. Finally, the gut microbiome's metabolism is not driven by a set of discrete linear pathways but a web of interconnected reactions facilitated by a network of enzymes that connect multiple molecules across multiple pathways.}, }
@article {pmid30732955, year = {2019}, author = {Healy, CM and Moran, GP}, title = {The microbiome and oral cancer: More questions than answers.}, journal = {Oral oncology}, volume = {89}, number = {}, pages = {30-33}, doi = {10.1016/j.oraloncology.2018.12.003}, pmid = {30732955}, issn = {1879-0593}, abstract = {Recent advances in DNA sequencing technology have facilitated rapid advances in the analysis of the human microbiome and its role in human disease. Several studies have now shown that OSCC and some oral premalignant conditions are associated with alterations in the oral microbiome. These studies raise questions regarding the role of the oral microbiome in the progression of oral malignancies and whether microbiome change is a significant risk factor in the development of oral cancer. This short review summarises current knowledge in the field and highlights questions that require further investigation.}, }
@article {pmid30731251, year = {2019}, author = {Bekker, V and Zwittink, RD and Knetsch, CW and Sanders, IMJG and Berghuis, D and Heidt, PJ and Vossen, JMJJ and de Vos, WM and Belzer, C and Bredius, RGM and Van't Hof, PJ and Lankester, AC and Kuijper, EJ}, title = {Dynamics of the Gut Microbiota in Children Receiving Selective or Total Gut Decontamination Treatment during Hematopoietic Stem Cell Transplantation.}, journal = {Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation}, volume = {25}, number = {6}, pages = {1164-1171}, doi = {10.1016/j.bbmt.2019.01.037}, pmid = {30731251}, issn = {1523-6536}, abstract = {Bloodstream infections and graft-versus-host disease are common complications after hematopoietic stem cell transplantation (HSCT) procedures, associated with the gut microbiota that acts as a reservoir for opportunistic pathogens. Selective gut decontamination (SGD) and total gut decontamination (TGD) during HSCT have been associated with a decreased risk of developing these complications after transplantation. However, because studies have shown conflicting results, the use of these treatments remains subject of debate. In addition, their impact on the gut microbiota is not well studied. The aim of this study was to elucidate the dynamics of the microbiota during and after TGD and to compare these with the dynamics of SGD. In this prospective, observational, single-center study fecal samples were longitudinally collected from 19 children eligible for allogenic HSCT (TGD, n=12; SGD, n=7), weekly during hospital admission and monthly after discharge. In addition, fecal samples were collected from 3 family stem cell donors. Fecal microbiota structure of patients and donors was determined by 16S rRNA gene amplicon sequencing. Microbiota richness and diversity markedly decreased during SGD and TGD and gradually increased after cessation of decontamination treatment. During SGD, gut microbiota composition was relatively stable and dominated by Bacteroides, whereas it showed high inter- and intraindividual variation and low Bacteroides abundance during TGD. In some children TGD allowed the genera Enterococcus and Streptococcus to thrive during treatment. A gut microbiota dominated by Bacteroides was associated with increased predicted activity of several metabolic processes. Comparing the microbiota of recipients and their donors indicated that receiving an SCT did not alter the patient's microbiota to become more similar to that of its donor. Overall, our findings indicate that SGD and TGD affect gut microbiota structure in a treatment-specific manner. Whether these treatments affect clinical outcomes via interference with the gut microbiota needs to be further elucidated.}, }
@article {pmid30728915, year = {2019}, author = {Lu, H and Ren, Z and Li, A and Li, J and Xu, S and Zhang, H and Jiang, J and Yang, J and Luo, Q and Zhou, K and Zheng, S and Li, L}, title = {Tongue coating microbiome data distinguish patients with pancreatic head cancer from healthy controls.}, journal = {Journal of oral microbiology}, volume = {11}, number = {1}, pages = {1563409}, doi = {10.1080/20002297.2018.1563409}, pmid = {30728915}, issn = {2000-2297}, abstract = {Background: The microbiota plays a critical role in the process of human carcinogenesis. Pancreatic head carcinoma (PHC)-associated tongue coating microbiome dysbiosis has not yet been clearly defined.Objective: Our aim is to reveal the bacterial composition shifts in the microbiota of the tongue coat of PHC patients.Design: The tongue coating microbiota was analyzed in 30 PHC patients and 25 healthy controls using 16S rRNA gene sequencing technology.Results: The microbiome diversity of the tongue coat in PHC patients was significantly increased, as shown by the Shannon, Simpson, inverse Simpson, Obs and incidence-based coverage estimators. Principal component analysis revealed that PHC patients were colonized by remarkably different tongue coating microbiota than healthy controls and liver cancer patients. Linear discriminant analysis effect size revealed that Leptotrichia, Fusobacterium,Rothia, Actinomyces, Corynebacterium, Atopobium, Peptostreptococcus, Catonella, Oribacterium, Filifactor, Campylobacter, Moraxella and Tannerella were overrepresented in the tongue coating of PHC patients, and Haemophilus, Porphyromonas and Paraprevotella were enriched in the tongue coating microbiota of healthy controls. Strikingly, Haemophilus, Porphyromonas, Leptotrichia and Fusobacterium could distinguish PHC patients from healthy subjects, and Streptococcus and SR1 could distinguish PHC patients from liver cancer patients. Conclusions: These findings identified the microbiota dysbiosis of the tongue coat in PHC patients, and provide insight into the association between the human microbiome and pancreatic cancer.}, }
@article {pmid30725462, year = {2019}, author = {Morales, E and Chen, J and Greathouse, KL}, title = {Compositional Analysis of the Human Microbiome in Cancer Research.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {1928}, number = {}, pages = {299-335}, doi = {10.1007/978-1-4939-9027-6_16}, pmid = {30725462}, issn = {1940-6029}, mesh = {Biological Evolution ; Gastrointestinal Microbiome ; Humans ; *Metagenome ; *Metagenomics/methods ; *Microbiota ; Polymerase Chain Reaction ; RNA, Ribosomal, 16S ; *Research ; }, abstract = {Gut microbial composition has shown to be associated with obesity, diabetes mellitus, inflammatory bowel disease, colitis, autoimmune disorders, and cancer, among other diseases. Microbiome research has significantly evolved through the years and continues to advance as we develop new and better strategies to more accurately measure its composition and function. Careful selection of study design, inclusion and exclusion criteria of participants, and methodology are paramount to accurately analyze microbial structure. Here we present the most up-to-date available information on methods for gut microbial collection and analysis.}, }
@article {pmid30718869, year = {2019}, author = {Forster, SC and Kumar, N and Anonye, BO and Almeida, A and Viciani, E and Stares, MD and Dunn, M and Mkandawire, TT and Zhu, A and Shao, Y and Pike, LJ and Louie, T and Browne, HP and Mitchell, AL and Neville, BA and Finn, RD and Lawley, TD}, title = {A human gut bacterial genome and culture collection for improved metagenomic analyses.}, journal = {Nature biotechnology}, volume = {37}, number = {2}, pages = {186-192}, doi = {10.1038/s41587-018-0009-7}, pmid = {30718869}, issn = {1546-1696}, mesh = {Bacteria/classification ; Computational Biology/methods ; Contig Mapping ; Gastrointestinal Microbiome ; *Genome, Bacterial ; Genome, Human ; Humans ; *Metagenome ; *Metagenomics ; Phylogeny ; RNA, Ribosomal, 16S/metabolism ; Sequence Analysis, DNA ; Species Specificity ; }, abstract = {Understanding gut microbiome functions requires cultivated bacteria for experimental validation and reference bacterial genome sequences to interpret metagenome datasets and guide functional analyses. We present the Human Gastrointestinal Bacteria Culture Collection (HBC), a comprehensive set of 737 whole-genome-sequenced bacterial isolates, representing 273 species (105 novel species) from 31 families found in the human gastrointestinal microbiota. The HBC increases the number of bacterial genomes derived from human gastrointestinal microbiota by 37%. The resulting global Human Gastrointestinal Bacteria Genome Collection (HGG) classifies 83% of genera by abundance across 13,490 shotgun-sequenced metagenomic samples, improves taxonomic classification by 61% compared to the Human Microbiome Project (HMP) genome collection and achieves subspecies-level classification for almost 50% of sequences. The improved resource of gastrointestinal bacterial reference sequences circumvents dependence on de novo assembly of metagenomes and enables accurate and cost-effective shotgun metagenomic analyses of human gastrointestinal microbiota.}, }
@article {pmid30710104, year = {2019}, author = {Du Toit, A}, title = {Expanding diversity of the human microbiome.}, journal = {Nature reviews. Microbiology}, volume = {17}, number = {3}, pages = {126}, doi = {10.1038/s41579-019-0154-0}, pmid = {30710104}, issn = {1740-1534}, }
@article {pmid30705670, year = {2018}, author = {Whittle, E and Leonard, MO and Harrison, R and Gant, TW and Tonge, DP}, title = {Multi-Method Characterization of the Human Circulating Microbiome.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {3266}, doi = {10.3389/fmicb.2018.03266}, pmid = {30705670}, issn = {1664-302X}, abstract = {The term microbiome describes the genetic material encoding the various microbial populations that inhabit our body. Whilst colonization of various body niches (e.g., the gut) by dynamic communities of microorganisms is now universally accepted, the existence of microbial populations in other &quot;classically sterile&quot; locations, including the blood, is a relatively new concept. The presence of bacteria-specific DNA in the blood has been reported in the literature for some time, yet the true origin of this is still the subject of much deliberation. The aim of this study was to investigate the phenomenon of a &quot;blood microbiome&quot; by providing a comprehensive description of bacterially derived nucleic acids using a range of complementary molecular and classical microbiological techniques. For this purpose we utilized a set of plasma samples from healthy subjects (n = 5) and asthmatic subjects (n = 5). DNA-level analyses involved the amplification and sequencing of the 16S rRNA gene. RNA-level analyses were based upon the de novo assembly of unmapped mRNA reads and subsequent taxonomic identification. Molecular studies were complemented by viability data from classical aerobic and anaerobic microbial culture experiments. At the phylum level, the blood microbiome was predominated by Proteobacteria, Actinobacteria, Firmicutes, and Bacteroidetes. The key phyla detected were consistent irrespective of molecular method (DNA vs. RNA), and consistent with the results of other published studies. In silico comparison of our data with that of the Human Microbiome Project revealed that members of the blood microbiome were most likely to have originated from the oral or skin communities. To our surprise, aerobic and anaerobic cultures were positive in eight of out the ten donor samples investigated, and we reflect upon their source. Our data provide further evidence of a core blood microbiome, and provide insight into the potential source of the bacterial DNA/RNA detected in the blood. Further, data reveal the importance of robust experimental procedures, and identify areas for future consideration.}, }
@article {pmid30701191, year = {2019}, author = {Leviatan, S and Segal, E}, title = {A Significant Expansion of Our Understanding of the Composition of the Human Microbiome.}, journal = {mSystems}, volume = {4}, number = {1}, pages = {}, doi = {10.1128/mSystems.00010-19}, pmid = {30701191}, issn = {2379-5077}, abstract = {Shotgun sequencing of samples taken from the human microbiome often reveals only partial mapping of the sequenced metagenomic reads to existing reference genomes. Such partial mappability indicates that many genomes are missing in our reference genome set. This is particularly true for non-Western populations and for samples that do not originate from the gut. Pasolli et al. (E. Pasolli, F. Asnicar, S. Manara, M. Zolfo, et al., Cell, 2019, https://doi.org/10.1016/j.cell.2019.01.001) perform a grand effort to expand the reference set, and to better classify its members, revealing a wider pangenome of existing species as well as identifying new species of previously unknown taxonomic branches.}, }
@article {pmid30700742, year = {2019}, author = {Tejesvi, MV and Nissi, R and Saravesi, K and Pirttilä, AM and Markkola, A and Talvensaari-Mattila, A and Ruotsalainen, AL}, title = {Association of prevalent vaginal microbiome of mother with occurrence of type I diabetes in child.}, journal = {Scientific reports}, volume = {9}, number = {1}, pages = {959}, doi = {10.1038/s41598-018-37467-w}, pmid = {30700742}, issn = {2045-2322}, support = {138309//Suomen Akatemia | Biotieteiden ja Ymp&amp;#x00E4;rist&amp;#x00F6;n Tutkimuksen Toimikunta (Research Council for Biosciences and Environment)/ ; }, abstract = {Type I diabetes (T1D) is a rapidly increasing autoimmune disease especially in the Western countries and poses a serious global health problem. Incidence of T1D cannot be fully explained by genetic background, and environmental factors have been assumed to play a role. Environmental conditions and composition of human microbiome have been found to correlate with the incidence of T1D. We asked whether mothers' prevalent vaginal microbiome could correlate with the incidence of T1D in child. To test this hypothesis, we collected samples of vaginal microbiomes from eight mothers that had at least one child with T1D (child age maximum of 11 years at the time of sampling), born with a vaginal delivery. Eight control mothers had child/children with vaginal delivery and no diabetic child/children. The microbiomes were studied by using 16S rRNA Ion Torrent high throughput sequencing. We found that composition of total and Lactobacillus microbiome was altered, and saw an indication that diversity of vaginal microbiomes of the mothers with a diabetic child could be higher. Based on these pilot observations, we strongly encourage a larger population study to verify whether mother vaginal microbiome diversity and composition are linked to the prevalence of T1D in children.}, }
@article {pmid30697198, year = {2018}, author = {Naradasu, D and Miran, W and Sakamoto, M and Okamoto, A}, title = {Isolation and Characterization of Human Gut Bacteria Capable of Extracellular Electron Transport by Electrochemical Techniques.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {3267}, doi = {10.3389/fmicb.2018.03267}, pmid = {30697198}, issn = {1664-302X}, abstract = {Microorganisms are known to exhibit extracellular electron transfer (EET) in a wide variety of habitats. However, as for the human microbiome which significantly impacts our health, the role and importance of EET has not been widely investigated. In this study, we enriched and isolated the EET-capable bacteria from human gut microbes using an electrochemical enrichment method and examined whether the isolates couple EET with anaerobic respiration or fermentation. Upon the use of energy-rich or minimum media (with acetate or lactate) for electrochemical enrichment with the human gut sample at an electrode potential of +0.4 V [vs. the standard hydrogen electrode (SHE)], both culture conditions showed significant current production. However, EET-capable pure strains were enriched specifically with minimum media, and subsequent incubation using the δ-MnO2-agar plate with lactate or acetate led to the isolation of two EET-capable microbial strains, Gut-S1 and Gut-S2, having 99% of 16S rRNA gene sequence identity with Enterococcus avium (E. avium) and Klebsiella pneumoniae (K. pneumoniae), respectively. While the enrichment involved anaerobic respiration with acetate and lactate, further electrochemistry with E. avium and K. pneumoniae revealed that the glucose fermentation was also coupled with EET. These results indicate that EET couples not only with anaerobic respiration as found in environmental bacteria, but also with fermentation in the human gut.}, }
@article {pmid30692672, year = {2019}, author = {Devoto, AE and Santini, JM and Olm, MR and Anantharaman, K and Munk, P and Tung, J and Archie, EA and Turnbaugh, PJ and Seed, KD and Blekhman, R and Aarestrup, FM and Thomas, BC and Banfield, JF}, title = {Megaphages infect Prevotella and variants are widespread in gut microbiomes.}, journal = {Nature microbiology}, volume = {4}, number = {4}, pages = {693-700}, doi = {10.1038/s41564-018-0338-9}, pmid = {30692672}, issn = {2058-5276}, support = {R01 AI092531/AI/NIAID NIH HHS/United States ; R21 AG055777/AG/NIA NIH HHS/United States ; }, mesh = {Adult ; Animals ; Bacteria/*virology ; Bacteriophages/classification/genetics/*isolation &amp; purification ; Female ; *Gastrointestinal Microbiome ; Genome, Viral ; Humans ; Male ; Metagenome ; *Microbiota ; Middle Aged ; Papio/*microbiology ; Phylogeny ; Prevotella/classification/genetics/*virology ; Swine/*microbiology ; }, abstract = {Bacteriophages (phages) dramatically shape microbial community composition, redistribute nutrients via host lysis and drive evolution through horizontal gene transfer. Despite their importance, much remains to be learned about phages in the human microbiome. We investigated the gut microbiomes of humans from Bangladesh and Tanzania, two African baboon social groups and Danish pigs; many of these microbiomes contain phages belonging to a clade with genomes >540 kilobases in length, the largest yet reported in the human microbiome and close to the maximum size ever reported for phages. We refer to these as Lak phages. CRISPR spacer targeting indicates that Lak phages infect bacteria of the genus Prevotella. We manually curated to completion 15 distinct Lak phage genomes recovered from metagenomes. The genomes display several interesting features, including use of an alternative genetic code, large intergenic regions that are highly expressed and up to 35 putative transfer RNAs, some of which contain enigmatic introns. Different individuals have distinct phage genotypes, and shifts in variant frequencies over consecutive sampling days reflect changes in the relative abundance of phage subpopulations. Recent homologous recombination has resulted in extensive genome admixture of nine baboon Lak phage populations. We infer that Lak phages are widespread in gut communities that contain the Prevotella species, and conclude that megaphages, with fascinating and underexplored biology, may be common but largely overlooked components of human and animal gut microbiomes.}, }
@article {pmid30687300, year = {2018}, author = {Woods, DF and Kozak, IM and Flynn, S and O'Gara, F}, title = {The Microbiome of an Active Meat Curing Brine.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {3346}, doi = {10.3389/fmicb.2018.03346}, pmid = {30687300}, issn = {1664-302X}, abstract = {Traditional food products are important to our culture and heritage, and to the continued success of the food industry. Many of the production processes associated with these products have not been subjected to an in-depth microbial compositional analysis. The traditional process of curing meat, both preserves a natural protein source, as well as increasing its organoleptic qualities. One of the most important salting processes is known as Wiltshire curing. The Wiltshire process involves injecting pork with a curing solution and immersing the meat into microbial-rich brine which promotes the development of the distinct organoleptic characteristics. The important microbial component of Wiltshire brine has not been extensively characterized. We analyzed the key microbial component of Wiltshire brine by performing microbiome analysis using Next Generation Sequencing (NGS) technologies. This analysis identified the genera, Marinilactibacillus, Carnobacterium, Leuconostoc, and Vibrio as the core microflora present in Wiltshire curing brine. The important food industrial applications of these bacteria were also assessed. The bacterial diversity of the brine was investigated, and the community composition of the brine was demonstrated to change over time. New knowledge on the characterization of key microbiota associated with a productive Wiltshire brine is an important development linked to promoting enhanced quality and safety of meat processing in the food industry.}, }
@article {pmid30687254, year = {2018}, author = {Forbes, JD and Bernstein, CN and Tremlett, H and Van Domselaar, G and Knox, NC}, title = {A Fungal World: Could the Gut Mycobiome Be Involved in Neurological Disease?.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {3249}, doi = {10.3389/fmicb.2018.03249}, pmid = {30687254}, issn = {1664-302X}, abstract = {The human microbiome has received decades of attention from scientific and medical research communities. The human gastrointestinal tract is host to immense populations of microorganisms including bacteria, viruses, archaea, and fungi (the gut microbiota). High-throughput sequencing and computational advancements provide unprecedented ability to investigate the structure and function of microbial communities associated with the human body in health and disease. Most research to date has largely focused on elucidating the bacterial component of the human gut microbiota. Study of the gut &quot;mycobiota,&quot; which refers to the diverse array of fungal species, is a relatively new and rapidly progressing field. Though omnipresent, the number and abundance of fungi occupying the human gut is orders of magnitude smaller than that of bacteria. Recent insights however, have suggested that the gut mycobiota may be intricately linked to health and disease. Evaluation of the gut mycobiota has shown that not only are the fungal communities altered in disease, but they also play a role in maintaining intestinal homeostasis and influencing systemic immunity. In addition, it is now widely accepted that host-fungi and bacteria-fungi associations are critical to host health. While research of the gut mycobiota in health and disease is on the rise, little research has been performed in the context of neuroimmune and neurodegenerative conditions. Gut microbiota dysbiosis (specifically bacteria and archaea) have been reported in neurological diseases such as multiple sclerosis, amyotrophic lateral sclerosis, and Alzheimer's, among others. Given the widely accepted bacteria-fungi associations and paucity of mycobiota-specific studies in neurological disease, this review discusses the potential role fungi may play in multiple sclerosis and other neurological diseases. Herein, we provide an overview of recent advances in gut mycobiome research and discuss the plausible role of both intestinal and non-intestinal fungi in the context of neuroimmune and neurodegenerative conditions.}, }
@article {pmid30675064, year = {2019}, author = {Tanoue, T and Morita, S and Plichta, DR and Skelly, AN and Suda, W and Sugiura, Y and Narushima, S and Vlamakis, H and Motoo, I and Sugita, K and Shiota, A and Takeshita, K and Yasuma-Mitobe, K and Riethmacher, D and Kaisho, T and Norman, JM and Mucida, D and Suematsu, M and Yaguchi, T and Bucci, V and Inoue, T and Kawakami, Y and Olle, B and Roberts, B and Hattori, M and Xavier, RJ and Atarashi, K and Honda, K}, title = {A defined commensal consortium elicits CD8 T cells and anti-cancer immunity.}, journal = {Nature}, volume = {565}, number = {7741}, pages = {600-605}, doi = {10.1038/s41586-019-0878-z}, pmid = {30675064}, issn = {1476-4687}, support = {DK43351/NH/NIH HHS/United States ; AT009708/NH/NIH HHS/United States ; }, mesh = {Adenocarcinoma/*immunology/pathology/*therapy ; Animals ; Antigens, CD/metabolism ; Bacteria/*classification/immunology/isolation &amp; purification ; CD8-Positive T-Lymphocytes/cytology/*immunology ; Cell Line, Tumor ; Dendritic Cells/immunology ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*immunology ; Healthy Volunteers ; Histocompatibility Antigens Class I/immunology ; Humans ; Integrin alpha Chains/metabolism ; Interferon-gamma/biosynthesis/immunology ; Listeria monocytogenes/immunology ; Listeriosis/immunology/microbiology/*prevention &amp; control ; Male ; Mice ; Programmed Cell Death 1 Receptor/antagonists &amp; inhibitors/immunology ; Symbiosis/*immunology ; Xenograft Model Antitumor Assays ; }, abstract = {There is a growing appreciation for the importance of the gut microbiota as a therapeutic target in various diseases. However, there are only a handful of known commensal strains that can potentially be used to manipulate host physiological functions. Here we isolate a consortium of 11 bacterial strains from healthy human donor faeces that is capable of robustly inducing interferon-γ-producing CD8 T cells in the intestine. These 11 strains act together to mediate the induction without causing inflammation in a manner that is dependent on CD103+ dendritic cells and major histocompatibility (MHC) class Ia molecules. Colonization of mice with the 11-strain mixture enhances both host resistance against Listeria monocytogenes infection and the therapeutic efficacy of immune checkpoint inhibitors in syngeneic tumour models. The 11 strains primarily represent rare, low-abundance components of the human microbiome, and thus have great potential as broadly effective biotherapeutics.}, }
@article {pmid30671046, year = {2018}, author = {Zhang, C and Thakkar, PV and Powell, SE and Sharma, P and Vennelaganti, S and Betel, D and Shah, MA}, title = {A Comparison of Homogenization vs. Enzymatic Lysis for Microbiome Profiling in Clinical Endoscopic Biopsy Tissue Samples.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {3246}, doi = {10.3389/fmicb.2018.03246}, pmid = {30671046}, issn = {1664-302X}, abstract = {Identification of the human microbiome has proven to be of utmost importance with the emerging role of bacteria in various physiological and pathological processes. High throughput sequencing strategies have evolved to assess the composition of the microbiome. To identify possible bias that may exist in the processing of tissue for whole genome sequencing (WGS), it is important to evaluate the extraction method on the overall microbial content and composition. Here we compare two different methods of extraction, homogenization vs. enzymatic lysis, on gastric, esophageal and colorectal biopsies and survey the microbial content and composition using WGS and quantitative PCR (qPCR). We examined total bacterial content using universal 16S rDNA qPCR as well as the abundance of three phyla (Actinobacter, Firmicutes, Bacteroidetes) and one genus (Fusobacterium). We found minimal differences between the two extraction methods in the overall community structure. Furthermore, based on our qPCR analysis, neither method demonstrated preferential extraction of any particular clade of bacteria, nor significantly altered the detection of Gram-positive or Gram-negative organisms. However, although the overall microbial composition remained very similar and the most prevalent bacteria could be detected effectively using either method, the precise community structure and microbial abundances between the two methods were different, primarily due to variations in detection of low abundance genus. We also demonstrate that the homogenization extraction method provides higher microbial DNA content and higher read counts from human tissue biopsy samples of the gastrointestinal tract.}, }
@article {pmid30670574, year = {2019}, author = {Dominguez-Bello, MG and Godoy-Vitorino, F and Knight, R and Blaser, MJ}, title = {Role of the microbiome in human development.}, journal = {Gut}, volume = {68}, number = {6}, pages = {1108-1114}, doi = {10.1136/gutjnl-2018-317503}, pmid = {30670574}, issn = {1468-3288}, mesh = {Biological Evolution ; Female ; Fetal Development/*physiology ; *Health Status ; *Human Development ; Humans ; Infant, Newborn ; Male ; Microbiota/*genetics/physiology ; Role ; }, abstract = {The host-microbiome supraorganism appears to have coevolved and the unperturbed microbial component of the dyad renders host health sustainable. This coevolution has likely shaped evolving phenotypes in all life forms on this predominantly microbial planet. The microbiota seems to exert effects on the next generation from gestation, via maternal microbiota and immune responses. The microbiota ecosystems develop, restricted to their epithelial niches by the host immune system, concomitantly with the host chronological development, providing early modulation of physiological host development and functions for nutrition, immunity and resistance to pathogens at all ages. Here, we review the role of the microbiome in human development, including evolutionary considerations, and the maternal/fetal relationships, contributions to nutrition and growth. We also discuss what constitutes a healthy microbiota, how antimicrobial modern practices are impacting the human microbiota, the associations between microbiota perturbations, host responses and diseases rocketing in urban societies and potential for future restoration.}, }
@article {pmid30666529, year = {2019}, author = {Bilen, M and Fonkou, MDM and Caputo, A and Nguyen, TT and Di Pinto, F and Bittar, F and Daoud, Z and Levasseur, A and Fournier, PE and Raoult, D and Cadoret, F}, title = {Phoenicibacter congonensis gen. nov., sp. nov., a new genus isolated from the human gut and its description using a taxonogenomic approach.}, journal = {Antonie van Leeuwenhoek}, volume = {112}, number = {5}, pages = {775-784}, doi = {10.1007/s10482-018-01211-1}, pmid = {30666529}, issn = {1572-9699}, support = {10-IAHU- 03//Agence Nationale de la Recherche/ ; FEDER PRIMI//Conseil R?gional Provence-Alpes-C?te d'Azur/ ; }, mesh = {Actinobacteria/*classification/genetics/*isolation &amp; purification ; Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Feces ; Female ; Gastrointestinal Microbiome ; Humans ; Middle Aged ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; }, abstract = {Culturomics has recently allowed the isolation and description of previously uncultured bacteria from the human microbiome at different body sites. As part of a project aiming to describe the human gut microbiota by culturomics, Phoenicibacter congonensis strain Marseille-P3241T was isolated from the gut of a 45 years old Pygmy female. In the present work, we aim to describe this strain via the taxonogenomics approach. The major phenotypic, genomic and biochemical characteristics of this strain were analysed. Strain Marseille-P3241T is an anaerobic, Gram-positive and motile coccobacillus that grows optimally at 37 °C. The genome of strain Marseille-P3241T is 1,447,956 bp long with 43.44% GC content and its 16S rRNA gene sequence exhibited 89% sequence similarity with that of Denitrobacterium detoxificans strain NPOH1T, the phylogenetically closest related species with current standing in nomenclature. After performing a phylogenetic and genomic analysis, we conclude that strain Marseille-P3241T (= CCUG 70681T = CSUR P3241T) represents the type species of a new genus, for which we propose the name Phoenicibacter congonensis gen. nov., sp. nov.}, }
@article {pmid30666248, year = {2018}, author = {Malla, MA and Dubey, A and Kumar, A and Yadav, S and Hashem, A and Abd Allah, EF}, title = {Exploring the Human Microbiome: The Potential Future Role of Next-Generation Sequencing in Disease Diagnosis and Treatment.}, journal = {Frontiers in immunology}, volume = {9}, number = {}, pages = {2868}, doi = {10.3389/fimmu.2018.02868}, pmid = {30666248}, issn = {1664-3224}, abstract = {The interaction between the human microbiome and immune system has an effect on several human metabolic functions and impacts our well-being. Additionally, the interaction between humans and microbes can also play a key role in determining the wellness or disease status of the human body. Dysbiosis is related to a plethora of diseases, including skin, inflammatory, metabolic, and neurological disorders. A better understanding of the host-microbe interaction is essential for determining the diagnosis and appropriate treatment of these ailments. The significance of the microbiome on host health has led to the emergence of new therapeutic approaches focused on the prescribed manipulation of the host microbiome, either by removing harmful taxa or reinstating missing beneficial taxa and the functional roles they perform. Culturing large numbers of microbial taxa in the laboratory is problematic at best, if not impossible. Consequently, this makes it very difficult to comprehensively catalog the individual members comprising a specific microbiome, as well as understanding how microbial communities function and influence host-pathogen interactions. Recent advances in sequencing technologies and computational tools have allowed an increasing number of metagenomic studies to be performed. These studies have provided key insights into the human microbiome and a host of other microbial communities in other environments. In the present review, the role of the microbiome as a therapeutic agent and its significance in human health and disease is discussed. Advances in high-throughput sequencing technologies for surveying host-microbe interactions are also discussed. Additionally, the correlation between the composition of the microbiome and infectious diseases as described in previously reported studies is covered as well. Lastly, recent advances in state-of-the-art bioinformatics software, workflows, and applications for analysing metagenomic data are summarized.}, }
@article {pmid30664484, year = {2019}, author = {Lauwers, L and Bastiaens, H and Remmen, R and Keune, H}, title = {The Integration of Interlinkages Between Nature and Human Health in Primary Health Care: Protocol for a Scoping Review.}, journal = {JMIR research protocols}, volume = {8}, number = {1}, pages = {e12510}, doi = {10.2196/12510}, pmid = {30664484}, issn = {1929-0748}, abstract = {BACKGROUND: International overview reports and the majority of scientific publications on interlinkages between nature and human health (NHI) do not seem to focus on the role of the health care sector. Primary health care (PHC) is often the first point of contact people have with the health care system and provides comprehensive, accessible, and community-based care that meets the health needs of individuals throughout their life. PHC is a vital backbone for linking knowledge and practice within the organization of health care. This scoping review aims to focus on the potential role of PHC in relation to NHI.<br><br>OBJECTIVE: The objective of this protocol is to present the method used to scope international overview reports and scientific publications on what is mentioned on the integration of NHI in PHC.<br><br>METHODS: The international overview reports have been screened for keywords relating to PHC. We developed a specific search strategy to scope scientific literature on NHI in relation to PHC. The scientific literature search ran in Web of Science (WOS) and PubMed from inception to May 2017. The scientific publications are screened by 2 independent reviewers, which will result in a list of relevant publications that meet eligibility and inclusion criteria.<br><br>RESULTS: On the basis of a first screen on the title of the first 200 results in both search engines, we decided to restrict to WOS. First insights in the international overview reports and the quantitative overview of the results in WOS give a first impression of a missing link between NHI and PHC. The findings are expected to identify knowledge gaps in the translation of evidence on NHI in PHC practices and the role of PHC regarding the application of that evidence in health care practice.<br><br>CONCLUSIONS: This is, to our knowledge, the first study that seeks to relate existing knowledge on NHI to PHC. The presentation of our method through this protocol allows researchers to build upon and improve our work in future research on the practical implementation of NIH. The findings of the scoping review are expected to guide future scientific research, international policy directives, and PHC workers to fill the gaps in the integration of NHI in PHC.<br><br>DERR1-10.2196/12510.}, }
@article {pmid30664014, year = {2019}, author = {Joris, BR and Gloor, GB}, title = {Unaccounted risk of cardiovascular disease: the role of the microbiome in lipid metabolism.}, journal = {Current opinion in lipidology}, volume = {30}, number = {2}, pages = {125-133}, doi = {10.1097/MOL.0000000000000582}, pmid = {30664014}, issn = {1473-6535}, abstract = {PURPOSE OF REVIEW: Not all of the risk of cardiovascular disease can be explained by diet and genetics, and the human microbiome, which lies at the interface of these two factors, may help explain some of the unaccounted risk. This review examines some of the well established links between the microbiome and cardiovascular health, and proposes relatively unexplored associations.<br><br>RECENT FINDINGS: Byproducts of microbial metabolism are associated with health and disease: Trimethylamine N oxide is associated with atherosclerosis; whereas short-chain fatty acids are associated with decreased inflammation and increased energy expenditure. More broadly, a large number of association studies have been conducted to explore the connections between bacterial taxa and metabolic syndrome. In contrast, the relationship between the microbiome and triglycerides levels remains poorly understood.<br><br>SUMMARY: We suggest that deeper understanding of the molecular mechanisms that drive linkages between the microbiome and disease can be determined by replacing 16S rRNA gene sequencing with shotgun metagenomic sequencing or other functional approaches. Furthermore, to ensure translatability and reproducibility of research findings, a combination of multiple different complementary '-omic' approaches should be employed.}, }
@article {pmid30661755, year = {2019}, author = {Pasolli, E and Asnicar, F and Manara, S and Zolfo, M and Karcher, N and Armanini, F and Beghini, F and Manghi, P and Tett, A and Ghensi, P and Collado, MC and Rice, BL and DuLong, C and Morgan, XC and Golden, CD and Quince, C and Huttenhower, C and Segata, N}, title = {Extensive Unexplored Human Microbiome Diversity Revealed by Over 150,000 Genomes from Metagenomes Spanning Age, Geography, and Lifestyle.}, journal = {Cell}, volume = {176}, number = {3}, pages = {649-662.e20}, doi = {10.1016/j.cell.2019.01.001}, pmid = {30661755}, issn = {1097-4172}, support = {MR/L015080/1//Medical Research Council/United Kingdom ; U54 DE023798/DE/NIDCR NIH HHS/United States ; R01 HG005220/HG/NHGRI NIH HHS/United States ; MR/M50161X/1//Medical Research Council/United Kingdom ; R24 DK110499/DK/NIDDK NIH HHS/United States ; }, abstract = {The body-wide human microbiome plays a role in health, but its full diversity remains uncharacterized, particularly outside of the gut and in international populations. We leveraged 9,428 metagenomes to reconstruct 154,723 microbial genomes (45% of high quality) spanning body sites, ages, countries, and lifestyles. We recapitulated 4,930 species-level genome bins (SGBs), 77% without genomes in public repositories (unknown SGBs [uSGBs]). uSGBs are prevalent (in 93% of well-assembled samples), expand underrepresented phyla, and are enriched in non-Westernized populations (40% of the total SGBs). We annotated 2.85 M genes in SGBs, many associated with conditions including infant development (94,000) or Westernization (106,000). SGBs and uSGBs permit deeper microbiome analyses and increase the average mappability of metagenomic reads from 67.76% to 87.51% in the gut (median 94.26%) and 65.14% to 82.34% in the mouth. We thus identify thousands of microbial genomes from yet-to-be-named species, expand the pangenomes of human-associated microbes, and allow better exploitation of metagenomic technologies.}, }
@article {pmid30660785, year = {2019}, author = {Marsh, RL and Smith-Vaughan, HC and Chen, ACH and Marchant, JM and Yerkovich, ST and Gibson, PG and Pizzutto, SJ and Hodge, S and Upham, JW and Chang, AB}, title = {Multiple Respiratory Microbiota Profiles Are Associated With Lower Airway Inflammation in Children With Protracted Bacterial Bronchitis.}, journal = {Chest}, volume = {155}, number = {4}, pages = {778-786}, doi = {10.1016/j.chest.2019.01.002}, pmid = {30660785}, issn = {1931-3543}, abstract = {BACKGROUND: Effective management of protracted bacterial bronchitis (PBB) is needed to prevent chronic disease (eg, bronchiectasis). Understanding the contributions of ongoing airway infection and inflammation is important to achieving optimal PBB treatments. The aim of this study was to compare BAL microbiota, bacterial biomass, and inflammatory markers in children with PBB and age-matched control patients.<br><br>METHODS: BAL was prospectively collected from 28 children with PBB (median age, 1.7 years; range, 0.6-7.4) and 8 control patients (median age, 1.9 years; range, 0.4-4.7). BAL microbiology was determined using culture, 16S ribosomal RNA gene sequencing and bacterial biomass quantification. BAL inflammatory cells, IL-8, and IL-1β were used to assess lower airway inflammation.<br><br>RESULTS: Bacterial biomass, neutrophil percentage, IL-8, and IL-1β levels were significantly higher in children with PBB compared with control patients. BAL microbiota in children with PBB was significantly different to that of control patients (permutational multivariate analysis of variance P = .001) and clustered into four distinct profiles that were either dominated by a respiratory pathogen or contained a more diverse microbiota including Prevotella species. Alpha diversity was unrelated to bacterial biomass, culture of recognized respiratory pathogens, or inflammatory markers.<br><br>CONCLUSIONS: Neutrophilic inflammation in children with PBB was associated with multiple BAL microbiota profiles. Significant associations between inflammatory markers and bacterial biomass, but not alpha diversity, suggest that inflammation in children with PBB is not driven by single pathogenic species. Understanding the role of the entire respiratory microbiota in PBB pathogenesis may be important to determining whether bacteria other than the recognized pathogens contribute to disease recurrence and progression to bronchiectasis.}, }
@article {pmid30658055, year = {2019}, author = {Pellock, SJ and Walton, WG and Ervin, SM and Torres-Rivera, D and Creekmore, BC and Bergan, G and Dunn, ZD and Li, B and Tripathy, A and Redinbo, MR}, title = {Discovery and Characterization of FMN-Binding β-Glucuronidases in the Human Gut Microbiome.}, journal = {Journal of molecular biology}, volume = {431}, number = {5}, pages = {970-980}, doi = {10.1016/j.jmb.2019.01.013}, pmid = {30658055}, issn = {1089-8638}, support = {R01 CA098468/CA/NCI NIH HHS/United States ; R01 CA161879/CA/NCI NIH HHS/United States ; R01 CA207416/CA/NCI NIH HHS/United States ; }, abstract = {The human gut microbiota encodes β-glucuronidases (GUSs) that play key roles in health and disease via the metabolism of glucuronate-containing carbohydrates and drugs. Hundreds of putative bacterial GUS enzymes have been identified by metagenomic analysis of the human gut microbiome, but less than 10% have characterized structures and functions. Here we describe a set of unique gut microbial GUS enzymes that bind flavin mononucleotide (FMN). First, we show using mass spectrometry, isothermal titration calorimetry, and x-ray crystallography that a purified GUS from the gut commensal microbe Faecalibacterium prausnitzii binds to FMN on a surface groove located 30 Å away from the active site. Second, utilizing structural and functional data from this FMN-binding GUS, we analyzed the 279 unique GUS sequences from the Human Microbiome Project database and identified 14 putative FMN-binding GUSs. We characterized four of these hits and solved the structure of two, the GUSs from Ruminococcus gnavus and Roseburia hominis, which confirmed that these are FMN binders. Third, binding and kinetic analysis of the FMN-binding site mutants of these five GUSs show that they utilize a conserved site to bind FMN that is not essential for GUS activity, but can affect KM. Lastly, a comprehensive structural review of the PDB reveals that the FMN-binding site employed by these enzymes is unlike any structurally characterized FMN binders to date. These findings reveal the first instance of an FMN-binding glycoside hydrolase and suggest a potential link between FMN and carbohydrate metabolism in the human gut microbiota.}, }
@article {pmid30657195, year = {2019}, author = {Espin-Garcia, O and Croitoru, K and Xu, W}, title = {A finite mixture model for X-chromosome association with an emphasis on microbiome data analysis.}, journal = {Genetic epidemiology}, volume = {43}, number = {4}, pages = {427-439}, doi = {10.1002/gepi.22190}, pmid = {30657195}, issn = {1098-2272}, support = {145546//CIHR/Canada ; GET-101831//CIHR/Canada ; CMF108031//CIHR/Canada ; }, mesh = {*Chromosomes, Human, X/genetics ; Cohort Studies ; Crohn Disease/epidemiology/genetics/microbiology ; Data Analysis ; Family ; Female ; Finite Element Analysis ; Gene-Environment Interaction ; Genetic Association Studies/statistics &amp; numerical data ; Genotype ; Heterozygote ; High-Throughput Nucleotide Sequencing ; Humans ; Male ; Microbiota/*genetics ; Models, Genetic ; X Chromosome Inactivation ; }, abstract = {Analysis of the X chromosome has been largely neglected in genetic studies mainly because of complex underlying biological mechanisms. On the other hand, the study of human microbiome data (typically over-dispersed counts with an excess of zeros) has generated great interest recently because of advancements in next-generation sequencing technologies. We propose a novel approach to infer the association between host genetic variants in the X-chromosome and microbiome data. The method accounts for random X-chromosome inactivation (XCI), skewed (or nonrandom) XCI (XCI-S), and escape of XCI (XCI-E). The inference is performed through a finite mixture model (FMM), in which an indicator variable denoting the &quot;true&quot; biological mechanism is treated as missing data. An expectation-maximization algorithm on zero-inflated and two-part models is implemented to estimate genetic effects. We investigate the performance of the FMM along with strategies that assume XCI and XCI-E mechanisms for all subjects compared with alternative approaches. Briefly, an XCI mechanism codes males' genotypes as homozygous females, whereas under XCI-E, males are treated as heterozygous females. By comprehensive simulations, we evaluate tests of the hypothesis under a computationally efficient score statistic. In summary, the FMM renders reduced bias and commensurate power compared to XCI, XCI-E, and alternative strategies while maintaining adequate Type 1 error control. The proposed method has far-reaching applications. In particular, we illustrate its usage on a large-scale human microbiome study, the Genetic, Environmental and Microbial (GEM) project, to test for the genetic association on the X chromosome.}, }
@article {pmid30650377, year = {2019}, author = {Britton, GJ and Contijoch, EJ and Mogno, I and Vennaro, OH and Llewellyn, SR and Ng, R and Li, Z and Mortha, A and Merad, M and Das, A and Gevers, D and McGovern, DPB and Singh, N and Braun, J and Jacobs, JP and Clemente, JC and Grinspan, A and Sands, BE and Colombel, JF and Dubinsky, MC and Faith, JJ}, title = {Microbiotas from Humans with Inflammatory Bowel Disease Alter the Balance of Gut Th17 and RORγt+ Regulatory T Cells and Exacerbate Colitis in Mice.}, journal = {Immunity}, volume = {50}, number = {1}, pages = {212-224.e4}, doi = {10.1016/j.immuni.2018.12.015}, pmid = {30650377}, issn = {1097-4180}, support = {P30 CA016087/CA/NCI NIH HHS/United States ; F30 DK108487/DK/NIDDK NIH HHS/United States ; UL1 TR000124/TR/NCATS NIH HHS/United States ; P30 CA016042/CA/NCI NIH HHS/United States ; P30 DK041301/DK/NIDDK NIH HHS/United States ; R01 DK085691/DK/NIDDK NIH HHS/United States ; R01 DK112978/DK/NIDDK NIH HHS/United States ; R01 GM108505/GM/NIGMS NIH HHS/United States ; F31 DK112679/DK/NIDDK NIH HHS/United States ; P01 DK046763/DK/NIDDK NIH HHS/United States ; P50 AT008661/AT/NCCIH NIH HHS/United States ; U24 AI118644/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Cell Differentiation ; Colitis/chemically induced/immunology/*microbiology ; Disease Models, Animal ; Disease Progression ; Gastrointestinal Microbiome/*genetics ; Homeostasis ; Humans ; Inflammatory Bowel Diseases/*immunology/*microbiology ; Mice ; Mice, Inbred C57BL ; Nuclear Receptor Subfamily 1, Group F, Member 3/metabolism ; RNA, Ribosomal, 16S/*genetics ; T-Lymphocytes, Regulatory/*immunology ; Th17 Cells/*metabolism ; }, abstract = {Microbiota are thought to influence the development and progression of inflammatory bowel disease (IBD), but determining generalizable effects of microbiota on IBD etiology requires larger-scale functional analyses. We colonized germ-free mice with intestinal microbiotas from 30 healthy and IBD donors and determined the homeostatic intestinal T cell response to each microbiota. Compared to microbiotas from healthy donors, transfer of IBD microbiotas into germ-free mice increased numbers of intestinal Th17 cells and Th2 cells and decreased numbers of RORγt+ Treg cells. Colonization with IBD microbiotas exacerbated disease in a model where colitis is induced upon transfer of naive T cells into Rag1-/- mice. The proportions of Th17 and RORγt+ Treg cells induced by each microbiota were predictive of human disease status and accounted for disease severity in the Rag1-/- colitis model. Thus, an impact on intestinal Th17 and RORγt+ Treg cell compartments emerges as a unifying feature of IBD microbiotas, suggesting a general mechanism for microbial contribution to IBD pathogenesis.}, }
@article {pmid30649168, year = {2019}, author = {Griffith, JC and Morgan, XC}, title = {Invited Commentary: Improving the Accessibility of Human Microbiome Project Data Through Integration With R/Bioconductor.}, journal = {American journal of epidemiology}, volume = {188}, number = {6}, pages = {1027-1030}, doi = {10.1093/aje/kwz007}, pmid = {30649168}, issn = {1476-6256}, abstract = {Alterations in the composition of the microbiota have been implicated in many diseases. The Human Microbiome Project (HMP) provides a comprehensive reference data set of the &quot;normal&quot; human microbiome of 242 healthy adults at 5 major body sites. The HMP used both 16S ribosomal RNA gene sequencing and whole-genome metagenomic sequencing to profile the subjects' microbial communities. However, accessing and analyzing the HMP data set still presents technical and bioinformatic challenges, given that researchers must import the microbiome data, integrate phylogenetic trees, and access and merge public and restricted metadata. The HMP16SData R/Bioconductor package developed by Schiffer et al. (Am J Epidemiol. 2019;188(6):1023-1026) greatly simplifies access to the HMP data by combining 16S taxonomic abundance data, public patient metadata, and phylogenetic trees as a single data object. The authors also provide an interface for users with approved Database of Genotypes and Phenotypes (dbGaP) projects to easily retrieve and merge the controlled-access HMP metadata. This package has a broad range of appeal to researchers across disciplines and with various levels of expertise in using R and/or other statistical tools, which translates to improved data accessibility for public health research, with data from healthy individuals serving as a reference for disease-associated studies.}, }
@article {pmid30649166, year = {2019}, author = {Schiffer, L and Azhar, R and Shepherd, L and Ramos, M and Geistlinger, L and Huttenhower, C and Dowd, JB and Segata, N and Waldron, L}, title = {HMP16SData: Efficient Access to the Human Microbiome Project Through Bioconductor.}, journal = {American journal of epidemiology}, volume = {188}, number = {6}, pages = {1023-1026}, doi = {10.1093/aje/kwz006}, pmid = {30649166}, issn = {1476-6256}, support = {R01 HG005220/HG/NHGRI NIH HHS/United States ; R21 AI121784/AI/NIAID NIH HHS/United States ; U24 CA180996/CA/NCI NIH HHS/United States ; U54 DE023798/DE/NIDCR NIH HHS/United States ; }, abstract = {Phase 1 of the Human Microbiome Project (HMP) investigated 18 body subsites of 242 healthy American adults to produce the first comprehensive reference for the composition and variation of the &quot;healthy&quot; human microbiome. Publicly available data sets from amplicon sequencing of two 16S ribosomal RNA variable regions, with extensive controlled-access participant data, provide a reference for ongoing microbiome studies. However, utilization of these data sets can be hindered by the complex bioinformatic steps required to access, import, decrypt, and merge the various components in formats suitable for ecological and statistical analysis. The HMP16SData package provides count data for both 16S ribosomal RNA variable regions, integrated with phylogeny, taxonomy, public participant data, and controlled participant data for authorized researchers, using standard integrative Bioconductor data objects. By removing bioinformatic hurdles of data access and management, HMP16SData enables epidemiologists with only basic R skills to quickly analyze HMP data.}, }
@article {pmid30644740, year = {2019}, author = {Brasili, E and Hassimotto, NMA and Del Chierico, F and Marini, F and Quagliariello, A and Sciubba, F and Miccheli, A and Putignani, L and Lajolo, F}, title = {Daily Consumption of Orange Juice from Citrus sinensis L. Osbeck cv. Cara Cara and cv. Bahia Differently Affects Gut Microbiota Profiling as Unveiled by an Integrated Meta-Omics Approach.}, journal = {Journal of agricultural and food chemistry}, volume = {67}, number = {5}, pages = {1381-1391}, doi = {10.1021/acs.jafc.8b05408}, pmid = {30644740}, issn = {1520-5118}, mesh = {Adult ; Bacteria/classification/genetics/isolation &amp; purification ; Brazil ; Citrus sinensis/chemistry/classification/*metabolism ; Female ; Fruit/chemistry/classification ; Fruit and Vegetable Juices/*analysis ; *Gastrointestinal Microbiome ; Gastrointestinal Tract/metabolism/microbiology ; Humans ; Male ; Middle Aged ; Young Adult ; }, abstract = {We have investigated the effect of intake of two different orange juices from Citrus sinensis cv. &quot;Cara Cara&quot; and cv. &quot;Bahia&quot; on faecal microbiota and metabolome using an integrated meta-omics approach. Following a randomized crossover design, healthy subjects daily consumed 500 mL of orange juice from Cara Cara or Bahia juices or an isocaloric control drink. Stools were collected at baseline (T0) and after a week (T7) of intervention. Operational taxonomic units (OTUs) were pyrosequenced targeting 16S rRNA, and faecal metabolites were analyzed by an untargeted metabolomics approach based on 1H NMR spectroscopy. The major shift observed in microbiota composition after orange juice intake was the increased abundance of a network of Clostridia OTUs from Mogibacteriaceae, Tissierellaceae, Veillonellaceae, Odoribacteraceae, and Ruminococcaceae families, whose members were differently affected by Cara Cara or Bahia juice consumption. A core of six metabolites such as inositol, choline, lysine, arginine, urocanic acid, and formate significantly increased in Cara Cara compared to the Bahia group.}, }
@article {pmid30643895, year = {2019}, author = {Gutiérrez-Barranquero, JA and Parages, ML and Dobson, ADW and Reen, FJ and O'Gara, F}, title = {Genome Sequence of Paracoccus sp. JM45, a Bacterial Strain Isolated from a Marine Sponge with a Dual Quorum Sensing Inhibition Activity.}, journal = {Microbiology resource announcements}, volume = {8}, number = {2}, pages = {}, doi = {10.1128/MRA.01496-18}, pmid = {30643895}, issn = {2576-098X}, abstract = {The draft genome sequence of Paracoccus sp. strain JM45, isolated from a marine sponge harvested off the west coast of Ireland, is reported here. Quorum sensing and quorum sensing inhibition activities have been reported recently for this bacterium, and genomic analysis supports its potential use for novel therapeutic development.}, }
@article {pmid30635376, year = {2019}, author = {Feng, S and McLellan, SL}, title = {Highly Specific Sewage-Derived Bacteroides Quantitative PCR Assays Target Sewage-Polluted Waters.}, journal = {Applied and environmental microbiology}, volume = {85}, number = {6}, pages = {}, doi = {10.1128/AEM.02696-18}, pmid = {30635376}, issn = {1098-5336}, support = {R01 AI091829/AI/NIAID NIH HHS/United States ; }, abstract = {The identification of sewage contamination in water has primarily relied on the detection of human-associated Bacteroides using markers within the V2 region of the 16S rRNA gene. Despite the establishment of multiple assays that target the HF183 cluster (i.e., Bacteroides dorei) and other Bacteroides organisms (e.g., Bacteroides thetaiotaomicron), the potential for more human-associated markers in this genus has not been explored in depth. We examined the Bacteroides population structure in sewage and animal hosts across the V4V5 and V6 hypervariable regions. Using near-full-length cloned sequences, we identified the sequences in the V4V5 and V6 hypervariable regions that are linked to the HF183 marker in the V2 region and found these sequences were present in multiple animals. In addition, the V4V5 and V6 regions contained human fecal marker sequences for organisms that were independent of the HF183 cluster. The most abundant Bacteroides in untreated sewage was not human associated but pipe derived. Two TaqMan quantitative PCR (qPCR) assays targeting the V4V5 and V6 regions of this organism were developed. Validation studies using fecal samples from seven animal hosts (n = 76) and uncontaminated water samples (n = 30) demonstrated the high specificity of the assays for sewage. Freshwater Bacteroides were also identified in uncontaminated water samples, demonstrating that measures of total Bacteroides do not reflect fecal pollution. A comparison of two previously described human Bacteroides assays (HB and HF183/BacR287) in municipal wastewater influent and sewage-contaminated urban water samples revealed identical results, illustrating the assays target the same organism. The detection of sewage-derived Bacteroides provided an independent measure of sewage-impacted waters.IMPORTANCEBacteroides are major members of the gut microbiota, and host-specific organisms within this genus have been used extensively to gain information on pollution sources. This study provides a broad view of the population structure of Bacteroides within sewage to contextualize the well-studied HF183 marker for a human-associated Bacteroides The study also delineates host-specific sequence patterns across multiple hypervariable regions of the 16S rRNA gene to improve our ability to use sequence data to assess water quality. Here, we demonstrate that regions downstream of the HF183 marker are nonspecific but other potential human-associated markers are present. Furthermore, we show the most abundant Bacteroides in sewage is free living, rather than host associated, and specifically found in sewage. Quantitative PCR assays that target organisms specific to sewer pipes offer measures that are independent of the human microbiome for identifying sewage pollution in water.}, }
@article {pmid30626617, year = {2019}, author = {Rowan-Nash, AD and Korry, BJ and Mylonakis, E and Belenky, P}, title = {Cross-Domain and Viral Interactions in the Microbiome.}, journal = {Microbiology and molecular biology reviews : MMBR}, volume = {83}, number = {1}, pages = {}, doi = {10.1128/MMBR.00044-18}, pmid = {30626617}, issn = {1098-5557}, support = {P20 GM109035/GM/NIGMS NIH HHS/United States ; P20 GM121344/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Archaea/metabolism/pathogenicity ; Bacteria/metabolism/pathogenicity ; Fungi/metabolism/pathogenicity ; Gastrointestinal Microbiome/*physiology ; *Gastrointestinal Tract/microbiology/parasitology/virology ; Helminths/metabolism/pathogenicity ; Host-Parasite Interactions/*physiology ; Humans ; Models, Animal ; Specific Pathogen-Free Organisms ; *Viruses/metabolism/pathogenicity ; }, abstract = {The importance of the microbiome to human health is increasingly recognized and has become a major focus of recent research. However, much of the work has focused on a few aspects, particularly the bacterial component of the microbiome, most frequently in the gastrointestinal tract. Yet humans and other animals can be colonized by a wide array of organisms spanning all domains of life, including bacteria and archaea, unicellular eukaryotes such as fungi, multicellular eukaryotes such as helminths, and viruses. As they share the same host niches, they can compete with, synergize with, and antagonize each other, with potential impacts on their host. Here, we discuss these major groups making up the human microbiome, with a focus on how they interact with each other and their multicellular host.}, }
@article {pmid30619299, year = {2018}, author = {Satitsuksanoa, P and Jansen, K and Głobińska, A and van de Veen, W and Akdis, M}, title = {Regulatory Immune Mechanisms in Tolerance to Food Allergy.}, journal = {Frontiers in immunology}, volume = {9}, number = {}, pages = {2939}, doi = {10.3389/fimmu.2018.02939}, pmid = {30619299}, issn = {1664-3224}, abstract = {Oral tolerance can develop after frequent exposure to food allergens. Upon ingestion, food is digested into small protein fragments in the gastrointestinal tract. Small food particles are later absorbed into the human body. Interestingly, some of these ingested food proteins can cause allergic immune responses, which can lead to food allergy. So far it has not been completely elucidated how these proteins become immunogenic and cause food allergies. In contrast, oral tolerance helps to prevent the pathologic reactions against different types of food antigens from animal or plant origin. Tolerance to food is mainly acquired by dendritic cells, epithelial cells in the gut, and the gut microbiome. A subset of CD103+ DCs is capable of inducing T regulatory cells (Treg cells) that express anti-inflammatory cytokines. Anergic T cells also contribute to oral tolerance, by reducing the number of effector cells. Similar to Treg cells, B regulatory cells (Breg cells) suppress effector T cells and contribute to the immune tolerance to food allergens. Furthermore, the human microbiome is an essential mediator in the induction of oral tolerance or food allergy. In this review, we outline the current understanding of regulatory immune mechanisms in oral tolerance. The biological changes reflecting early consequences of immune stimulation with food allergens should provide useful information for the development of novel therapeutic treatments.}, }
@article {pmid30619188, year = {2018}, author = {Xiao, J and Chen, L and Yu, Y and Zhang, X and Chen, J}, title = {A Phylogeny-Regularized Sparse Regression Model for Predictive Modeling of Microbial Community Data.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {3112}, doi = {10.3389/fmicb.2018.03112}, pmid = {30619188}, issn = {1664-302X}, support = {U01 FD005875/FD/FDA HHS/United States ; }, abstract = {Fueled by technological advancement, there has been a surge of human microbiome studies surveying the microbial communities associated with the human body and their links with health and disease. As a complement to the human genome, the human microbiome holds great potential for precision medicine. Efficient predictive models based on microbiome data could be potentially used in various clinical applications such as disease diagnosis, patient stratification and drug response prediction. One important characteristic of the microbial community data is the phylogenetic tree that relates all the microbial taxa based on their evolutionary history. The phylogenetic tree is an informative prior for more efficient prediction since the microbial community changes are usually not randomly distributed on the tree but tend to occur in clades at varying phylogenetic depths (clustered signal). Although community-wide changes are possible for some conditions, it is also likely that the community changes are only associated with a small subset of &quot;marker&quot; taxa (sparse signal). Unfortunately, predictive models of microbial community data taking into account both the sparsity and the tree structure remain under-developed. In this paper, we propose a predictive framework to exploit sparse and clustered microbiome signals using a phylogeny-regularized sparse regression model. Our approach is motivated by evolutionary theory, where a natural correlation structure among microbial taxa exists according to the phylogenetic relationship. A novel phylogeny-based smoothness penalty is proposed to smooth the coefficients of the microbial taxa with respect to the phylogenetic tree. Using simulated and real datasets, we show that our method achieves better prediction performance than competing sparse regression methods for sparse and clustered microbiome signals.}, }
@article {pmid30604388, year = {2019}, author = {Osman, AEG and Luke, JJ}, title = {The Impact of the Fecal Microbiome on Cancer Immunotherapy.}, journal = {BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy}, volume = {33}, number = {1}, pages = {1-7}, doi = {10.1007/s40259-018-0328-8}, pmid = {30604388}, issn = {1179-190X}, support = {W81XWH-17-1-0265//U.S. Department of Defense/ ; }, mesh = {Gastrointestinal Microbiome/*immunology ; Graft vs Host Disease ; Humans ; Immunotherapy/methods ; Neoplasms/*microbiology/*therapy ; }, abstract = {Recent advances in culture-free methods of studying the human microbiome, coupled with strong bioinformatics tools, have provided new insights on the role of the human microbiome in health and disease. The human gut, in particular, houses a vast number and diverse variety of microbes. A plethora of evidence has demonstrated the significant effects of the gut microbiome on local and systemic immunity. Studies in hematopoietic stem cell transplantation recipients provided early evidence of the involvement of the gut microbiome in the development of graft-versus-host disease and its related mortality. Cancer immunotherapy and checkpoint inhibitors, in particular, harness the power of the host's immune system to fight a range of malignancies. Resistance to immunotherapy and fatal immune-related adverse events both continue to be challenges in the field. The role of the human gut microbiome in affecting the response to immunotherapy was recently uncovered through a series of preclinical and clinical studies. The evidence presented in these studies provides tremendous potential for gut microbes to be used for biomarker development and therapeutic intervention trials.}, }
@article {pmid30588567, year = {2019}, author = {Wei, F and Wu, Q and Hu, Y and Huang, G and Nie, Y and Yan, L}, title = {Conservation metagenomics: a new branch of conservation biology.}, journal = {Science China. Life sciences}, volume = {62}, number = {2}, pages = {168-178}, doi = {10.1007/s11427-018-9423-3}, pmid = {30588567}, issn = {1869-1889}, abstract = {Multifaceted approaches are required to monitor wildlife populations and improve conservation efforts. In the last decade, increasing evidence suggests that metagenomic analysis offers valuable perspectives and tools for identifying microbial communities and functions. It has become clear that gut microbiome plays a critical role in health, nutrition, and physiology of wildlife, including numerous endangered animals in the wild and in captivity. In this review, we first introduce the human microbiome and metagenomics, highlighting the importance of microbiome for host fitness. Then, for the first time, we propose the concept of conservation metagenomics, an emerging subdiscipline of conservation biology, which aims to understand the roles of the microbiota in evolution and conservation of endangered animals. We define what conservation metagenomics is along with current approaches, main scientific issues and significant implications in the study of host evolution, physiology, nutrition, ecology and conservation. We also discuss future research directions of conservation metagenomics. Although there is still a long way to go, conservation metagenomics has already shown a significant potential for improving the conservation and management of wildlife.}, }
@article {pmid30584647, year = {2019}, author = {Zhang, J and Zhang, F and Zhao, C and Xu, Q and Liang, C and Yang, Y and Wang, H and Shang, Y and Wang, Y and Mu, X and Zhu, D and Zhang, C and Yang, J and Yao, M and Zhang, L}, title = {Dysbiosis of the gut microbiome is associated with thyroid cancer and thyroid nodules and correlated with clinical index of thyroid function.}, journal = {Endocrine}, volume = {64}, number = {3}, pages = {564-574}, doi = {10.1007/s12020-018-1831-x}, pmid = {30584647}, issn = {1559-0100}, support = {31471202//the National Natural Science Foundation of China/ ; 81670822//the National Natural Science Foundation of China/ ; 2016YYSP009//the Shandong Provincial Key Research and Development Program/ ; 2016GNS023//Weihai Technique Extension Project/ ; 17-3-3-10-nsh//Qingdao Key Research Project/ ; tshw20120206//the Taishan Scholars Program of Shandong Province/ ; }, abstract = {PURPOSE: Thyroid cancer and thyroid nodules are the most prevalent form of thyroid endocrine disorder. The balance of gut microbiome is highly crucial for a healthy human body, especially for the immune and endocrine system. However, the relationship between gut microbiome and the thyroid endocrine disorders such as thyroid cancer and thyroid nodules has not been reported yet.<br><br>METHODS: A cohort of 74 patients was recruited for this study. Among them, 20 patients had thyroid cancer, 18 patients had thyroid nodules, and 36 were matched healthy controls. Gut microbiome composition was analyzed by 16S rRNA (16S ribosomal RNA) gene-based sequencing protocol.<br><br>RESULTS: We compared the gut microbiome results of 74 subjects and established the correlation between gut microbiome and thyroid endocrine function for both thyroid cancer and thyroid nodules. The results inferred that alpha and beta diversity were different for patients with thyroid tumor than the healthy controls (p < 0.01). In comparison to healthy controls, the relative abundance of Neisseria (p < 0.001) and Streptococcus (p < 0.001) was significantly higher for thyroid cancer and thyroid nodules. Butyricimonas (p < 0.001) and Lactobacillus (p < 0.001) displayed notably lower relative abundance for thyroid cancer and thyroid nodules, respectively. It was also found that the clinical indexes were correlated with gut microbiome.<br><br>CONCLUSION: Our results indicate that both thyroid cancer and thyroid nodules are associated with the composition of gut microbiome. These results may support further clinical diagnosis to a great extent and help in developing potential probiotics to facilitate the treatment of thyroid cancer and thyroid nodules.}, }
@article {pmid30578461, year = {2019}, author = {Nobili, V and Mosca, A and Alterio, T and Cardile, S and Putignani, L}, title = {Fighting Fatty Liver Diseases with Nutritional Interventions, Probiotics, Symbiotics, and Fecal Microbiota Transplantation (FMT).}, journal = {Advances in experimental medicine and biology}, volume = {1125}, number = {}, pages = {85-100}, doi = {10.1007/5584_2018_318}, pmid = {30578461}, issn = {0065-2598}, mesh = {*Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Non-alcoholic Fatty Liver Disease/*therapy ; Probiotics/*therapeutic use ; Randomized Controlled Trials as Topic ; }, abstract = {Pediatric obesity is rising worldwide leading the worrying phenomenon of nonalcoholic fatty liver disease (NAFLD) to shift into one of the most frequent causes of chronic liver illness in childhood. Occurrence of NAFLD depends on several factors such as the geographical area and the diagnostic modalities used; overall it ranges between 3% and 10% of pediatric population, increasing up to 70% in patients with metabolic comorbidities (Manco M, Bottazzo G, DeVito R et al, J Am Coll Nutr 27:667-676, 2008).Recent findings have related the intestinal microbiota to a plethora of pathological conditions, including type 2 diabetes (T2D), obesity, and nonalcoholic steatohepatitis (NASH). One of the emerging areas of the study is the link between liver diseases and gut microbiome, which has added new information to the understanding of the so-called gut-liver axis.In order to address the role of gut microbiome in NAFLD onset and progression, it is necessary to &quot;decipher&quot; operational codes for microbiome investigation within the context of advanced laboratory medicine to capture microbiome features and, hence, to address the function of the intestinal microbiome within the gut microbiota-liver axis.Results of these investigations have allowed the beginning of implementing the usage of probiotics and symbiotics in the medical approach of obesity and NAFLD in adults and children. Several randomized clinical trials (RCTs) have been already published on fecal microbiota transplantation (FMT), T2D, NASH, and inflammatory bowel disease (IBD).This review proposes to describe the current state of knowledge on the ways fatty liver diseases can be addressed with nutritional interventions, probiotics, symbiotics, and FMT.}, }
@article {pmid30578265, year = {2019}, author = {Stubbendieck, RM and May, DS and Chevrette, MG and Temkin, MI and Wendt-Pienkowski, E and Cagnazzo, J and Carlson, CM and Gern, JE and Currie, CR}, title = {Competition among Nasal Bacteria Suggests a Role for Siderophore-Mediated Interactions in Shaping the Human Nasal Microbiota.}, journal = {Applied and environmental microbiology}, volume = {85}, number = {10}, pages = {}, doi = {10.1128/AEM.02406-18}, pmid = {30578265}, issn = {1098-5336}, support = {P01 HL070831/HL/NHLBI NIH HHS/United States ; T15 LM007359/LM/NLM NIH HHS/United States ; T32 GM008505/GM/NIGMS NIH HHS/United States ; U19 AI109673/AI/NIAID NIH HHS/United States ; }, abstract = {Resources available in the human nasal cavity are limited. Therefore, to successfully colonize the nasal cavity, bacteria must compete for scarce nutrients. Competition may occur directly through interference (e.g., antibiotics) or indirectly by nutrient sequestration. To investigate the nature of nasal bacterial competition, we performed coculture inhibition assays between nasal Actinobacteria and Staphylococcus spp. We found that isolates of coagulase-negative staphylococci (CoNS) were sensitive to growth inhibition by Actinobacteria but that Staphylococcus aureus isolates were resistant to inhibition. Among Actinobacteria, we observed that Corynebacterium spp. were variable in their ability to inhibit CoNS. We sequenced the genomes of 10 Corynebacterium species isolates, including 3 Corynebacterium propinquum isolates that strongly inhibited CoNS and 7 other Corynebacterium species isolates that only weakly inhibited CoNS. Using a comparative genomics approach, we found that the C. propinquum genomes were enriched in genes for iron acquisition and harbored a biosynthetic gene cluster (BGC) for siderophore production, absent in the noninhibitory Corynebacterium species genomes. Using a chrome azurol S assay, we confirmed that C. propinquum produced siderophores. We demonstrated that iron supplementation rescued CoNS from inhibition by C. propinquum, suggesting that inhibition was due to iron restriction through siderophore production. Through comparative metabolomics and molecular networking, we identified the siderophore produced by C. propinquum as dehydroxynocardamine. Finally, we confirmed that the dehydroxynocardamine BGC is expressed in vivo by analyzing human nasal metatranscriptomes from the NIH Human Microbiome Project. Together, our results suggest that bacteria produce siderophores to compete for limited available iron in the nasal cavity and improve their fitness.IMPORTANCE Within the nasal cavity, interference competition through antimicrobial production is prevalent. For instance, nasal Staphylococcus species strains can inhibit the growth of other bacteria through the production of nonribosomal peptides and ribosomally synthesized and posttranslationally modified peptides. In contrast, bacteria engaging in exploitation competition modify the external environment to prevent competitors from growing, usually by hindering access to or depleting essential nutrients. As the nasal cavity is a nutrient-limited environment, we hypothesized that exploitation competition occurs in this system. We determined that Corynebacterium propinquum produces an iron-chelating siderophore, and this iron-sequestering molecule correlates with the ability to inhibit the growth of coagulase-negative staphylococci. Furthermore, we found that the genes required for siderophore production are expressed in vivo Thus, although siderophore production by bacteria is often considered a virulence trait, our work indicates that bacteria may produce siderophores to compete for limited iron in the human nasal cavity.}, }
@article {pmid30577530, year = {2018}, author = {Yang, AJ and Marito, S and Yang, JJ and Keshari, S and Chew, CH and Chen, CC and Huang, CM}, title = {A Microtube Array Membrane (MTAM) Encapsulated Live Fermenting Staphylococcus epidermidis as a Skin Probiotic Patch against Cutibacterium acnes.}, journal = {International journal of molecular sciences}, volume = {20}, number = {1}, pages = {}, doi = {10.3390/ijms20010014}, pmid = {30577530}, issn = {1422-0067}, support = {106-2320-B-008, 105-2314-B-008-001, 101-2221-E-038-009-, 107-2314-B-008 -001, 107-2622-B-008-002-CC1 and 106/107-2622-B-008-001-CC1//Ministry of Science and Technology, Taiwan/ ; NHRI-EX106-10607SI//NHRI/ ; }, mesh = {Animals ; *Antibiosis ; Chemokine CXCL2/metabolism ; Dermatitis/metabolism/microbiology ; Fermentation ; Glycerol/metabolism ; Humans ; Mice ; *Probiotics ; Propionibacteriaceae/*physiology ; Skin/*microbiology ; Staphylococcus epidermidis/*physiology ; }, abstract = {Antibiotics without selectivity for acne treatment may destroy the beneficial microbes in the human microbiome that helps to fight Cutibacterium acnes (C. acnes), a bacterium associated with inflammatory acne vulgaris. Probiotic treatment by direct application of live Staphylococcus epidermidis (S. epidermidis) onto the open acne lesions may run the risk of bloodstream infections. Here, we fabricated the polysulfone microtube array membranes (PSF MTAM) to encapsulate probiotic S.epidermidis. We demonstrate that the application of the encapsulation of S.epidermidis in PSF MTAM enhanced the glycerol fermentation activities of S. epidermidis. To mimic the granulomatous type of acne inflammatory acne vulgaris, the ears of mice were injected intradermally with C.acnes to induce the secretion of macrophage inflammatory protein-2 (MIP-2), a murine counterpart of human interleukin (IL)-8. The C. acnes-injected mouse ears were covered with a PST MTAM encapsulated with or without S.epidermidis in the presence of glycerol. The application of S.epidermidis-encapsulated PST MTAM plus glycerol onto the C.acnes-injected mouse ears considerably reduced the growth of C. acnes and the production of MIP-2. Furthermore, no S. epidermidis leaked from PSF MTAM into mouse skin. The S. epidermidis-encapsulated PST MTAM functions as a probiotic acne patch.}, }
@article {pmid30575732, year = {2018}, author = {Coryell, M and McAlpine, M and Pinkham, NV and McDermott, TR and Walk, ST}, title = {The gut microbiome is required for full protection against acute arsenic toxicity in mouse models.}, journal = {Nature communications}, volume = {9}, number = {1}, pages = {5424}, doi = {10.1038/s41467-018-07803-9}, pmid = {30575732}, issn = {2041-1723}, support = {F31 ES026884/ES/NIEHS NIH HHS/United States ; R01 CA215784/CA/NCI NIH HHS/United States ; R21 ES026411/ES/NIEHS NIH HHS/United States ; }, mesh = {Adult ; Animals ; Arsenic/metabolism ; Arsenic Poisoning/*prevention &amp; control ; Faecalibacterium prausnitzii/*physiology ; *Fecal Microbiota Transplantation ; Female ; *Gastrointestinal Microbiome ; *Germ-Free Life ; Humans ; Inactivation, Metabolic ; Male ; Methyltransferases/physiology ; Mice, Inbred C57BL ; Mice, Transgenic ; Young Adult ; }, abstract = {Arsenic poisons an estimated 200 million people worldwide through contaminated food and drinking water. Confusingly, the gut microbiome has been suggested to both mitigate and exacerbate arsenic toxicity. Here, we show that the microbiome protects mice from arsenic-induced mortality. Both antibiotic-treated and germ-free mice excrete less arsenic in stool and accumulate more arsenic in organs compared to control mice. Mice lacking the primary arsenic detoxification enzyme (As3mt) are hypersensitive to arsenic after antibiotic treatment or when derived germ-free, compared to wild-type and/or conventional counterparts. Human microbiome (stool) transplants protect germ-free As3mt-KO mice from arsenic-induced mortality, but protection depends on microbiome stability and the presence of specific bacteria, including Faecalibacterium. Our results demonstrate that both a functional As3mt and specific microbiome members are required for protection against acute arsenic toxicity in mouse models. We anticipate that the gut microbiome will become an important explanatory factor of disease (arsenicosis) penetrance in humans, and a novel target for prevention and treatment strategies.}, }
@article {pmid30573380, year = {2019}, author = {Altomare, A and Putignani, L and Del Chierico, F and Cocca, S and Angeletti, S and Ciccozzi, M and Tripiciano, C and Dalla Piccola, B and Cicala, M and Guarino, MPL}, title = {Gut mucosal-associated microbiota better discloses inflammatory bowel disease differential patterns than faecal microbiota.}, journal = {Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver}, volume = {51}, number = {5}, pages = {648-656}, doi = {10.1016/j.dld.2018.11.021}, pmid = {30573380}, issn = {1878-3562}, abstract = {BACKGROUND: Growing evidence supports the potential role of intestinal microbiota in the pathophysiology of inflammatory bowel diseases (IBD) even if the literature does not reveal uniform alterations. The aim of the study was to evaluate the mucosal (MM) and faecal microbiota (FM) composition in a cohort of IBD patients compared to healthy controls (CTRLs).<br><br>METHODS: Faecal and mucosal samples were collected from 14 IBD patients and 11 CTRLs. The V1-V3 region of 16S rRNA locus was amplified on a 454-Junior Genome Sequencer. Reads were grouped into operational taxonomic units (OTUs) at a sequence similarity level of 97% for taxonomic assignment, and aligned for OTUs matching against Greengenes database.<br><br>RESULTS: Irrespective of disease localization and activity, in the MM of IBD patients a statistically significant increase of Proteobacteria (especially Enterobacteriaceae, Acidaminococcus, Veillonella dispar) and decrease of Firmicutes (especially Roseburia and Faecalibacterium prausnitzii) and Actinobacteria was found compared to CTRLs. In the colon district some specific bacterial biomarkers were identified: Enterobacteriaceae for IBD stools, Bacteroides for IBD biopsies, Mogibacteriaceae, Ruminococcaceae and Prevotella for CTRL stools, Ruminococcaceae for CTRL biopsies.<br><br>CONCLUSIONS: The profiles of FM were more similar to CTRLs, suggesting that microbiota adhering to the gut mucosa better discriminates patients from controls, with the identification of some interesting biomarkers.}, }
@article {pmid30572622, year = {2018}, author = {Sánchez-Ponce, Y and Varela-Fascinetto, G and Romo-Vázquez, JC and López-Martínez, B and Sánchez-Huerta, JL and Parra-Ortega, I and Fuentes-Pananá, EM and Morales-Sánchez, A}, title = {Simultaneous Detection of Beta and Gamma Human Herpesviruses by Multiplex qPCR Reveals Simple Infection and Coinfection Episodes Increasing Risk for Graft Rejection in Solid Organ Transplantation.}, journal = {Viruses}, volume = {10}, number = {12}, pages = {}, doi = {10.3390/v10120730}, pmid = {30572622}, issn = {1999-4915}, mesh = {Adolescent ; Child ; Coinfection/*diagnosis/virology ; DNA Primers/genetics ; DNA, Viral/blood ; Epstein-Barr Virus Infections/*diagnosis/virology ; Female ; Graft Rejection/*etiology/virology ; Herpesvirus 4, Human/genetics ; Herpesvirus 6, Human/genetics ; Herpesvirus 7, Human/genetics ; Humans ; Male ; Multiplex Polymerase Chain Reaction ; Organ Transplantation/*adverse effects ; Prospective Studies ; Roseolovirus Infections/*diagnosis/virology ; Sensitivity and Specificity ; Viral Load ; }, abstract = {Herpesviruses are common components of the human microbiome that become clinically relevant when a competent immunosurveillance is compromised, such as in transplantation. Members of the beta and gamma subfamilies are associated with a wide diversity of pathologies, including end-organ disease and cancer. In this study, we developed a multiplex qPCR technique with high specificity, sensitivity, efficiency and predictability that allowed the simultaneous detection and quantification of beta and gamma human herpesviruses. The technique was tested in a cohort of 34 kidney- or liver-transplanted pediatric patients followed up for up to 12 months post-transplant. Viral load was determined in 495 leukocyte-plasma paired samples collected bi-weekly or monthly. Human herpesvirus (HHV) 7 was the herpesvirus most frequently found in positive samples (39%), followed by Epstein-Barr virus (EBV) (20%). Also, EBV and HHV7 were present in the majority of coinfection episodes (62%). The share of positive samples exclusively detected either in leukocytes or plasma was 85%, suggesting that these herpesviruses tended to take a latent or lytic path in an exclusive manner. Infection by human cytomegalovirus (HCMV) and HHV6, as well as coinfection by EBV/HHV7 and EBV/HHV6/HHV7, were associated with graft rejection (RR = 40.33 (p = 0.0013), 5.60 (p = 0.03), 5.60 (p = 0.03) and 17.64 (p = 0.0003), respectively). The routine monitoring of beta and gamma herpesviruses should be mandatory in transplant centers to implement preventive strategies.}, }
@article {pmid30564562, year = {2018}, author = {Proal, A and Marshall, T}, title = {Myalgic Encephalomyelitis/Chronic Fatigue Syndrome in the Era of the Human Microbiome: Persistent Pathogens Drive Chronic Symptoms by Interfering With Host Metabolism, Gene Expression, and Immunity.}, journal = {Frontiers in pediatrics}, volume = {6}, number = {}, pages = {373}, doi = {10.3389/fped.2018.00373}, pmid = {30564562}, issn = {2296-2360}, abstract = {The illness ME/CFS has been repeatedly tied to infectious agents such as Epstein Barr Virus. Expanding research on the human microbiome now allows ME/CFS-associated pathogens to be studied as interacting members of human microbiome communities. Humans harbor these vast ecosystems of bacteria, viruses and fungi in nearly all tissue and blood. Most well-studied inflammatory conditions are tied to dysbiosis or imbalance of the human microbiome. While gut microbiome dysbiosis has been identified in ME/CFS, microbes and viruses outside the gut can also contribute to the illness. Pathobionts, and their associated proteins/metabolites, often control human metabolism and gene expression in a manner that pushes the body toward a state of illness. Intracellular pathogens, including many associated with ME/CFS, drive microbiome dysbiosis by directly interfering with human transcription, translation, and DNA repair processes. Molecular mimicry between host and pathogen proteins/metabolites further complicates this interference. Other human pathogens disable mitochondria or dysregulate host nervous system signaling. Antibodies and/or clonal T cells identified in patients with ME/CFS are likely activated in response to these persistent microbiome pathogens. Different human pathogens have evolved similar survival mechanisms to disable the host immune response and host metabolic pathways. The metabolic dysfunction driven by these organisms can result in similar clusters of inflammatory symptoms. ME/CFS may be driven by this pathogen-induced dysfunction, with the nature of dysbiosis and symptom presentation varying based on a patient's unique infectious and environmental history. Under such conditions, patients would benefit from treatments that support the human immune system in an effort to reverse the infectious disease process.}, }
@article {pmid30559213, year = {2018}, author = {Tedijanto, C and Olesen, SW and Grad, YH and Lipsitch, M}, title = {Estimating the proportion of bystander selection for antibiotic resistance among potentially pathogenic bacterial flora.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {51}, pages = {E11988-E11995}, doi = {10.1073/pnas.1810840115}, pmid = {30559213}, issn = {1091-6490}, support = {R01 AI132606/AI/NIAID NIH HHS/United States ; U01 CK000538/CK/NCEZID CDC HHS/United States ; U01CK000538//ACL HHS/United States ; U54 GM088558/GM/NIGMS NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Anti-Bacterial Agents/immunology/*pharmacology ; Bacteria/classification/*drug effects/immunology ; Child ; Child, Preschool ; Drug Resistance, Bacterial/*drug effects/immunology ; Escherichia coli/drug effects ; Humans ; Infant ; Infant, Newborn ; Microbial Sensitivity Tests/methods ; Microbiota/*drug effects/immunology ; Pneumococcal Infections ; Pneumococcal Vaccines/immunology ; Species Specificity ; Staphylococcus aureus/drug effects ; Streptococcus pneumoniae/drug effects ; United States ; Vaccination ; Vaccines, Conjugate/immunology ; Young Adult ; }, abstract = {Bystander selection-the selective pressure for resistance exerted by antibiotics on microbes that are not the target pathogen of treatment-is critical to understanding the total impact of broad-spectrum antibiotic use on pathogenic bacterial species that are often carried asymptomatically. However, to our knowledge, this effect has never been quantified. We quantify bystander selection for resistance for a range of clinically relevant antibiotic-species pairs as the proportion of all antibiotic exposures received by a species for conditions in which that species was not the causative pathogen (&quot;proportion of bystander exposures&quot;). Data sources include the 2010-2011 National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey, the Human Microbiome Project, and additional carriage and etiological data from existing literature. For outpatient prescribing in the United States, we find that this proportion over all included antibiotic classes is over 80% for eight of nine organisms of interest. Low proportions of bystander exposure are often associated with infrequent bacterial carriage or concentrated prescribing of a particular antibiotic for conditions caused by the species of interest. Applying our results, we roughly estimate that pneumococcal conjugate vaccination programs result in nearly the same proportional reduction in total antibiotic exposures of Streptococcus pneumoniae, Staphylococcus aureus, and Escherichia coli, despite the latter two organisms not being targeted by the vaccine. These results underscore the importance of considering antibiotic exposures of bystanders, in addition to the target pathogen, in measuring the impact of antibiotic resistance interventions.}, }
@article {pmid30559176, year = {2018}, author = {Relman, DA and Lipsitch, M}, title = {Microbiome as a tool and a target in the effort to address antimicrobial resistance.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {51}, pages = {12902-12910}, doi = {10.1073/pnas.1717163115}, pmid = {30559176}, issn = {1091-6490}, support = {R01 AI112401/AI/NIAID NIH HHS/United States ; R01 GM099534/GM/NIGMS NIH HHS/United States ; }, mesh = {Anti-Infective Agents/*pharmacology ; Communicable Disease Control/*methods ; Communicable Diseases/drug therapy ; Drug Resistance, Microbial/*drug effects/genetics ; Host Microbial Interactions/drug effects/genetics/immunology ; Humans ; Microbiota/*drug effects ; Vaccines/*therapeutic use ; }, abstract = {Reciprocal, intimate relationships between the human microbiome and the host immune system are shaped by past microbial encounters and prepare the host for future ones. Antibiotics and other antimicrobials leave their mark on both the microbiome and host immunity. Antimicrobials alter the structure of the microbiota, expand the host-specific pool of antimicrobial-resistance genes and organisms, degrade the protective effects of the microbiota against invasion by pathogens, and may impair vaccine efficacy. Through these effects on the microbiome they may affect immune responses. Vaccines that exert protective or therapeutic effects against pathogens may reduce the use of antimicrobials, the development and spread of antimicrobial resistance, and the harmful impacts of these drugs on the microbiome. Other strategies involving manipulation of the microbiome to deplete antibiotic-resistant organisms or to enhance immune responses to vaccines may prove valuable in addressing antimicrobial resistance as well. This article describes the intersections of immunity, microbiome and antimicrobial exposure, and the use of vaccines and other alternative strategies for the control and management of antimicrobial resistance.}, }
@article {pmid30551740, year = {2018}, author = {Romani, L and Pane, S and Severini, C and Menegon, M and Foglietta, G and Bernardi, S and Tchidjou, HK and Onetti Muda, A and Palma, P and Putignani, L}, title = {Challenging diagnosis of congenital malaria in non-endemic areas.}, journal = {Malaria journal}, volume = {17}, number = {1}, pages = {470}, doi = {10.1186/s12936-018-2614-9}, pmid = {30551740}, issn = {1475-2875}, support = {RC2018//Bambino Gesù Children's Hospital/ ; }, mesh = {Communicable Diseases, Imported/*diagnosis/parasitology ; Fetal Diseases/*diagnosis/parasitology ; Humans ; Infant ; Italy ; Malaria, Falciparum/*diagnosis/epidemiology ; Male ; Plasmodium falciparum/isolation &amp; purification ; Polymerase Chain Reaction ; }, abstract = {BACKGROUND: Congenital malaria is usually defined as the detection of asexual forms of Plasmodium spp. in a blood sample of a neonate during perinatal age if there is no possibility of postpartum infection by a mosquito bite. The incidence of congenital malaria is highly variable and seems related to several factors, such as different diagnostic methods for Plasmodium spp. detection, and area in which the epidemiologic analyses are performed. In non-endemic countries, cases of congenital malaria are rare. Hereby, a case of a congenital malaria in an HIV exposed child is reported.<br><br>CASE PRESENTATION: A 2-month-old male child was admitted to Bambino Gesù Children's Hospital due to anaemia and exposure to HIV. He was born prematurely in Italy by cesarean section at 34 weeks' gestation after a bicorial, biamniotic pregnancy by a migrant woman from Nigeria. He was the first of non-identical twins. Combined with anaemia, spleen and liver enlargement was noted, malaria was hypothesized. Malaria laboratory panel was performed on the newborn, mother and other twin blood samples, as follows: (i) malaria rapid diagnostic test (RDT); (ii) Giemsa-stained thick and thin blood smears for Plasmodium spp. identification and parasitaemia titration; (iii) molecular screening and typing of Plasmodium spp. by multiplex qualitative PCR assay based on 18S rRNA gene. Genotyping of Plasmodium falciparum isolates from mother and child was performed by neutral microsatellite and highly polymorphic marker amplification.<br><br>CONCLUSIONS: The maternal RDT sample was negative, while the infant RDT was positive; in both cases microscopy of blood smears and PCR showed infection with P. falciparum. Two of the genotypic molecular markers displayed different allelic variants between the two samples. This difference could imply infection multiplicity of the mother during the pregnancy, possibly harbouring more than one isolate, only one of them being transmitted to the newborn while the other persisting in the mother's blood. Because of the increasing number of pregnant women coming from endemic areas for malaria, an accurate anamnesis of infant's mother, and the inclusion of Plasmodium spp. research into TORCH screenings for mother-infant pair at birth, aiming at reducing morbidity and mortality associated to the disease might be suitable.}, }
@article {pmid30544936, year = {2018}, author = {D'Argenio, V}, title = {The Prenatal Microbiome: A New Player for Human Health.}, journal = {High-throughput}, volume = {7}, number = {4}, pages = {}, doi = {10.3390/ht7040038}, pmid = {30544936}, issn = {2571-5135}, abstract = {The last few years have featured an increasing interest in the study of the human microbiome and its correlations with health status. Indeed, technological advances have allowed the study of microbial communities to reach a previously unthinkable sensitivity, showing the presence of microbes also in environments usually considered as sterile. In this scenario, microbial communities have been described in the amniotic fluid, the umbilical blood cord, and the placenta, denying a dogma of reproductive medicine that considers the uterus like a sterile womb. This prenatal microbiome may play a role not only in fetal development but also in the predisposition to diseases that may develop later in life, and also in adulthood. Thus, the aim of this review is to report the current knowledge regarding the prenatal microbiome composition, its association with pathological processes, and the future perspectives regarding its manipulation for healthy status promotion and maintenance.}, }
@article {pmid30524957, year = {2018}, author = {Yang, J and Mu, X and Wang, Y and Zhu, D and Zhang, J and Liang, C and Chen, B and Wang, J and Zhao, C and Zuo, Z and Heng, X and Zhang, C and Zhang, L}, title = {Dysbiosis of the Salivary Microbiome Is Associated With Non-smoking Female Lung Cancer and Correlated With Immunocytochemistry Markers.}, journal = {Frontiers in oncology}, volume = {8}, number = {}, pages = {520}, pmid = {30524957}, issn = {2234-943X}, abstract = {Background: Association between oral bacteria and increased risk of lung cancer have been reported in several previous studies, however, the potential association between salivary microbiome and lung cancer in non-smoking women have not been evaluated. There is also no report on the relationship between immunocytochemistry markers and salivary microbiota. Method: In this study, we assessed the salivary microbiome of 75 non-smoking female lung cancer patients and 172 matched healthy individuals using 16S rRNA gene amplicon sequencing. We also calculated the Spearman's rank correlation coefficient between salivary microbiota and three immunohistochemical markers (TTF-1, Napsin A and CK7). Result: We analyzed the salivary microbiota of 247 subjects and found that non-smoking female lung cancer patients exhibited oral microbial dysbiosis. There was significantly lower microbial diversity and richness in lung cancer patients when compared to the control group (Shannon index, P < 0.01; Ace index, P < 0.0001). Based on the analysis of similarities, the composition of the microbiota in lung cancer patients also differed from that of the control group (r = 0.454, P < 0.001, unweighted UniFrac; r = 0.113, P < 0.01, weighted UniFrac). The bacterial genera Sphingomonas (P < 0.05) and Blastomonas (P < 0.0001) were relatively higher in non-smoking female lung cancer patients, whereas Acinetobacter (P < 0.001) and Streptococcus (P < 0.01) were higher in controls. Based on Spearman's correlation analysis, a significantly positive correlation can be observed between CK7 and Enterobacteriaceae (r = 0.223, P < 0.05). At the same time, Napsin A was positively associated with genera Blastomonas (r = 0.251, P < 0.05). TTF-1 exhibited a significantly positive correlation with Enterobacteriaceae (r = 0.262, P < 0.05). Functional analysis from inferred metagenomes indicated that oral microbiome in non-smoking female lung cancer patients were related to cancer pathways, p53 signaling pathway, apoptosis and tuberculosis. Conclusions: The study identified distinct salivary microbiome profiles in non-smoking female lung cancer patients, revealed potential correlations between salivary microbiome and immunocytochemistry markers used in clinical diagnostics, and provided proof that salivary microbiota can be an informative source for discovering non-invasive lung cancer biomarkers.}, }
@article {pmid30534599, year = {2018}, author = {Escapa, IF and Chen, T and Huang, Y and Gajare, P and Dewhirst, FE and Lemon, KP}, title = {New Insights into Human Nostril Microbiome from the Expanded Human Oral Microbiome Database (eHOMD): a Resource for the Microbiome of the Human Aerodigestive Tract.}, journal = {mSystems}, volume = {3}, number = {6}, pages = {}, pmid = {30534599}, issn = {2379-5077}, support = {R01 DE024468/DE/NIDCR NIH HHS/United States ; R01 GM117174/GM/NIGMS NIH HHS/United States ; R37 DE016937/DE/NIDCR NIH HHS/United States ; UL1 TR001102/TR/NCATS NIH HHS/United States ; }, abstract = {The expanded Human Oral Microbiome Database (eHOMD) is a comprehensive microbiome database for sites along the human aerodigestive tract that revealed new insights into the nostril microbiome. The eHOMD provides well-curated 16S rRNA gene reference sequences linked to available genomes and enables assignment of species-level taxonomy to most next-generation sequences derived from diverse aerodigestive tract sites, including the nasal passages, sinuses, throat, esophagus, and mouth. Using minimum entropy decomposition coupled with the RDP Classifier and our eHOMD V1-V3 training set, we reanalyzed 16S rRNA V1-V3 sequences from the nostrils of 210 Human Microbiome Project participants at the species level, revealing four key insights. First, we discovered that Lawsonella clevelandensis, a recently named bacterium, and Neisseriaceae [G-1] HMT-174, a previously unrecognized bacterium, are common in adult nostrils. Second, just 19 species accounted for 90% of the total sequences from all participants. Third, 1 of these 19 species belonged to a currently uncultivated genus. Fourth, for 94% of the participants, 2 to 10 species constituted 90% of their sequences, indicating that the nostril microbiome may be represented by limited consortia. These insights highlight the strengths of the nostril microbiome as a model system for studying interspecies interactions and microbiome function. Also, in this cohort, three common nasal species (Dolosigranulum pigrum and two Corynebacterium species) showed positive differential abundance when the pathobiont Staphylococcus aureus was absent, generating hypotheses regarding colonization resistance. By facilitating species-level taxonomic assignment to microbes from the human aerodigestive tract, the eHOMD is a vital resource enhancing clinical relevance of microbiome studies. IMPORTANCE The eHOMD (http://www.ehomd.org) is a valuable resource for researchers, from basic to clinical, who study the microbiomes and the individual microbes in body sites in the human aerodigestive tract, which includes the nasal passages, sinuses, throat, esophagus, and mouth, and the lower respiratory tract, in health and disease. The eHOMD is an actively curated, web-based, open-access resource. eHOMD provides the following: (i) species-level taxonomy based on grouping 16S rRNA gene sequences at 98.5% identity, (ii) a systematic naming scheme for unnamed and/or uncultivated microbial taxa, (iii) reference genomes to facilitate metagenomic, metatranscriptomic, and proteomic studies and (iv) convenient cross-links to other databases (e.g., PubMed and Entrez). By facilitating the assignment of species names to sequences, the eHOMD is a vital resource for enhancing the clinical relevance of 16S rRNA gene-based microbiome studies, as well as metagenomic studies.}, }
@article {pmid30532649, year = {2018}, author = {Lim, MY and Cho, Y and Rho, M}, title = {Diverse Distribution of Resistomes in the Human and Environmental Microbiomes.}, journal = {Current genomics}, volume = {19}, number = {8}, pages = {701-711}, pmid = {30532649}, issn = {1389-2029}, abstract = {The routine therapeutic use of antibiotics has caused resistance genes to be disseminated across microbial populations. In particular, bacterial strains having antibiotic resistance genes are frequently observed in the human microbiome. Moreover, multidrug-resistant pathogens are now widely spread, threatening public health. Such genes are transferred and spread among bacteria even in different environments. Advances in high throughput sequencing technology and computational algorithms have accelerated investigation into antibiotic resistance genes of bacteria. Such studies have revealed that the antibiotic resistance genes are located close to the mobility-associated genes, which promotes their dissemination. An increasing level of information on genomic sequences of resistome should expedite research on drug-resistance in our body and environment, thereby contributing to the development of public health policy. In this review, the high prevalence of antibiotic resistance genes and their exchange in the human and environmental microbiome is discussed with respect to the genomic contents. The relationships among diverse resistomes, related bacterial species, and the antibiotics are reviewed. In addition, recent advances in bioinformatics approaches to investigate such relationships are discussed.}, }
@article {pmid30530088, year = {2019}, author = {Ben, Y and Fu, C and Hu, M and Liu, L and Wong, MH and Zheng, C}, title = {Human health risk assessment of antibiotic resistance associated with antibiotic residues in the environment: A review.}, journal = {Environmental research}, volume = {169}, number = {}, pages = {483-493}, doi = {10.1016/j.envres.2018.11.040}, pmid = {30530088}, issn = {1096-0953}, abstract = {The extensive use of antibiotics leading to the rapid spread of antibiotic resistance poses high health risks to humans, but to date there is still lack of a quantitative model to properly assess the risks. Concerns over the health risk of antibiotic residues in the environment are mainly (1) the potential hazard of ingested antibiotic residues in the environment altering the human microbiome and promoting emergence and selection for bacteria resistance inhabiting the human body, and (2) the potential hazard of creating a selection pressure on environmental microbiome and leading to reservoirs of antibiotic resistance in the environment. We provide a holistic view of health risk assessment of antibiotic resistance associated with antibiotic residues in the environment in contrast with that of the antibiotic resistant bacteria and discuss the main knowledge gaps and the future research that should be prioritized to achieve the quantitative risk assessment. We examined and summarized the available data and information on the four core elements of antibiotic resistance associated with antibiotic residues in the environment: hazard identification, exposure assessment, dose-response assessment, and risk characterization. The data required to characterize the risks of antibiotic residues in the environment is severely limited. The main future research needs have been identified to enable better assessments of antibiotic resistance associated with antibiotic residues in the environment: (1) establishment of a standardized monitoring guide of antibiotic residues and antibiotic resistance in the environment, (2) derivation of the relationship between antibiotic levels and pathogenic antibiotic-resistance development in different settings, and (3) establishment of the dose-response relationship between pathogenic antibiotic resistant bacteria and various infection diseases. After identification of key risk determinant parameters, we propose a conceptual framework of human health risk assessments of antibiotic residues in the environment. CAPSULE: A holistic view of human health risk assessment of antibiotic residues in the environment was provided.}, }
@article {pmid30529020, year = {2019}, author = {Robertson, RC and Manges, AR and Finlay, BB and Prendergast, AJ}, title = {The Human Microbiome and Child Growth - First 1000 Days and Beyond.}, journal = {Trends in microbiology}, volume = {27}, number = {2}, pages = {131-147}, doi = {10.1016/j.tim.2018.09.008}, pmid = {30529020}, issn = {1878-4380}, abstract = {The assembly of microbial communities within the gastrointestinal tract during early life plays a critical role in immune, endocrine, metabolic, and other host developmental pathways. Environmental insults during this period, such as food insecurity and infections, can disrupt this optimal microbial succession, which may contribute to lifelong and intergenerational deficits in growth and development. Here, we review the human microbiome in the first 1000 days - referring to the period from conception to 2 years of age - and using a developmental model, we examine the role of early microbial succession in growth and development. We propose that an 'undernourished' microbiome is intergenerational, thereby perpetuating growth impairments into successive generations. We also identify and discuss the intertwining host-microbe-environment interactions occurring prenatally and during early infancy, which may impair the trajectories of healthy growth and development, and explore their potential as novel microbial targets for intervention.}, }
@article {pmid30526758, year = {2018}, author = {Blaser, MJ}, title = {Our missing microbes: Short-term antibiotic courses have long-term consequences.}, journal = {Cleveland Clinic journal of medicine}, volume = {85}, number = {12}, pages = {928-930}, doi = {10.3949/ccjm.85gr.18005}, pmid = {30526758}, issn = {1939-2869}, mesh = {Anti-Bacterial Agents/*adverse effects ; Humans ; Long Term Adverse Effects/*chemically induced/microbiology ; Microbiota/*drug effects ; }, }
@article {pmid30521647, year = {2018}, author = {Jeżewska-Frąckowiak, J and Seroczyńska, K and Banaszczyk, J and Jedrzejczak, G and Żylicz-Stachula, A and Skowron, PM}, title = {The promises and risks of probiotic Bacillus species.}, journal = {Acta biochimica Polonica}, volume = {65}, number = {4}, pages = {509-519}, doi = {10.18388/abp.2018_2652}, pmid = {30521647}, issn = {1734-154X}, mesh = {Bacillus/classification/genetics/*physiology ; Biofilms ; Drug Resistance, Bacterial ; Gastrointestinal Diseases/*microbiology/*prevention &amp; control ; *Gastrointestinal Microbiome ; Humans ; Probiotics/*administration &amp; dosage/*adverse effects/standards ; RNA, Ribosomal, 16S/genetics ; Risk ; }, abstract = {Supplementing the human microbiome with probiotic microorganisms is a proposed solution for civilization syndromes such as dysbiosis and gastrointestinal tract (GIT) disorders. Bimodal probiotic strains of the Bacillus genus constitute the microbiota of the human environment, and are typically found in soil, water, a number of non-dairy fermented foods, as well as in human and animal GIT. Probiotic Bacillus sp. are Gram positive rods, with the ability of sporulation to survive environmental stress and preparation conditions. In vitro models of the human stomach and human studies with probiotic Bacillus reveal the mechanisms of its life cycle and sporulation. The Bacillus sp. probiotic biofilm introduces biochemical effects such as antimicrobial and enzymatic activity, thus contributing to protection from GIT and other infections. Despite the beneficial activity of Bacillus strains belonging to the safety group 1, a number of strains can pose a substantial health risk, carrying genes for various toxins or antibiotic resistance. Commercially available Bacillus probiotic preparations include strains from the subtilis and other closely related phylogenetic clades. Those intended for oral administration in humans, often encapsulated with appropriate supporting materials, still tend to be mislabeled or poorly characterized. Bacillus sp. MALDI-TOF analysis, combined with sequencing of characteristic 16S rRNA or enzyme coding genes, may provide accurate identification. A promising future application of the probiotic Bacillus sp. might be the microflora biocontrol in the human body and the closest human environment. Environmental probiotic Bacillus species display the potential to support human microflora, however controversies regarding the safety of certain strains is a key factor in their still limited application.}, }
@article {pmid30521551, year = {2018}, author = {Vernocchi, P and Del Chierico, F and Russo, A and Majo, F and Rossitto, M and Valerio, M and Casadei, L and La Storia, A and De Filippis, F and Rizzo, C and Manetti, C and Paci, P and Ercolini, D and Marini, F and Fiscarelli, EV and Dallapiccola, B and Lucidi, V and Miccheli, A and Putignani, L}, title = {Gut microbiota signatures in cystic fibrosis: Loss of host CFTR function drives the microbiota enterophenotype.}, journal = {PloS one}, volume = {13}, number = {12}, pages = {e0208171}, doi = {10.1371/journal.pone.0208171}, pmid = {30521551}, issn = {1932-6203}, mesh = {Anti-Bacterial Agents/adverse effects ; Bacteria/*isolation &amp; purification ; Child, Preschool ; Cohort Studies ; Cystic Fibrosis/drug therapy/genetics/*physiopathology ; Cystic Fibrosis Transmembrane Conductance Regulator/*genetics ; Dysbiosis/microbiology/physiopathology ; Exocrine Pancreatic Insufficiency/genetics/physiopathology ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/drug effects/*physiology ; Host Microbial Interactions/physiology ; Humans ; Intestinal Mucosa/microbiology/*physiopathology ; Male ; Metabolomics ; Metagenomics ; Phenotype ; }, abstract = {BACKGROUND: Cystic fibrosis (CF) is a disorder affecting the respiratory, digestive, reproductive systems and sweat glands. This lethal hereditary disease has known or suspected links to the dysbiosis gut microbiota. High-throughput meta-omics-based approaches may assist in unveiling this complex network of symbiosis modifications.<br><br>OBJECTIVES: The aim of this study was to provide a predictive and functional model of the gut microbiota enterophenotype of pediatric patients affected by CF under clinical stability.<br><br>METHODS: Thirty-one fecal samples were collected from CF patients and healthy children (HC) (age range, 1-6 years) and analysed using targeted-metagenomics and metabolomics to characterize the ecology and metabolism of CF-linked gut microbiota. The multidimensional data were low fused and processed by chemometric classification analysis.<br><br>RESULTS: The fused metagenomics and metabolomics based gut microbiota profile was characterized by a high abundance of Propionibacterium, Staphylococcus and Clostridiaceae, including Clostridium difficile, and a low abundance of Eggerthella, Eubacterium, Ruminococcus, Dorea, Faecalibacterium prausnitzii, and Lachnospiraceae, associated with overexpression of 4-aminobutyrate (GABA), choline, ethanol, propylbutyrate, and pyridine and low levels of sarcosine, 4-methylphenol, uracil, glucose, acetate, phenol, benzaldehyde, and methylacetate. The CF gut microbiota pattern revealed an enterophenotype intrinsically linked to disease, regardless of age, and with dysbiosis uninduced by reduced pancreatic function and only partially related to oral antibiotic administration or lung colonization/infection.<br><br>CONCLUSIONS: All together, the results obtained suggest that the gut microbiota enterophenotypes of CF, together with endogenous and bacterial CF biomarkers, are direct expression of functional alterations at the intestinal level. Hence, it's possible to infer that CFTR impairment causes the gut ecosystem imbalance.This new understanding of CF host-gut microbiota interactions may be helpful to rationalize novel clinical interventions to improve the affected children's nutritional status and intestinal function.}, }
@article {pmid30519775, year = {2019}, author = {Slobodin, G and Rosner, I and Kessel, A}, title = {Dendritic cells in the pathogenesis of ankylosing spondylitis and axial spondyloarthritis.}, journal = {Clinical rheumatology}, volume = {38}, number = {5}, pages = {1231-1235}, doi = {10.1007/s10067-018-4388-4}, pmid = {30519775}, issn = {1434-9949}, abstract = {The interaction of dendritic cells (DCs) with the human microbiome, with distorted handling of the microbiota or its products via the direct effect of HLA B27, probably represents the initial element in the chain of events leading to the development of clinical axial spondyloarthritis. The mechanism of disease extension onto the skeleton and other tissues involved, such as uvea, may also involve migratory DCs. Finally, the role of DCs in the initiation of the inflammatory tissue response with activation of the IL-17 axis has been demonstrated. Further, some initial data suggests the possible connection of DCs with disease-related new bone formation.}, }
@article {pmid30507717, year = {2019}, author = {Lai, PS and Christiani, DC}, title = {Impact of occupational exposure on human microbiota.}, journal = {Current opinion in allergy and clinical immunology}, volume = {19}, number = {2}, pages = {86-91}, doi = {10.1097/ACI.0000000000000502}, pmid = {30507717}, issn = {1473-6322}, support = {K23 ES023700/ES/NIEHS NIH HHS/United States ; R01 AI144119/AI/NIAID NIH HHS/United States ; }, abstract = {PURPOSE OF REVIEW: Recent evidence suggests that environmental exposures change the adult human microbiome. Here, we review recent evidence on the impact of the work microbiome and work-related chemical, metal and particulate exposures on the human microbiome.<br><br>RECENT FINDINGS: Prior literature on occupational microbial exposures has focused mainly on the respiratory effects of endotoxin, but a recent study suggests that not all endotoxin is the same; endotoxin from some species is proinflammatory, whereas endotoxin from other species is anti-inflammatory. Work with animals can change the adult human microbiome, likely through colonization. Early studies in military personnel and animal models of gulf war illness show that military exposures change the gut microbiome and increase gut permeability. Heavy metal and particulate matter exposure, which are often elevated in occupational settings, also change the gut microbiome.<br><br>SUMMARY: An emerging body of literature shows that work-related exposures can change the human microbiome. The health effects of these changes are currently not well studied. If work exposures lead to disease through alterations in the human microbiome, exposure cessation without addressing changes to the human microbiome may be ineffective for disease prevention and treatment.}, }
@article {pmid30514510, year = {2018}, author = {O'Toole, RF and Gautam, SS}, title = {The host microbiome and impact of tuberculosis chemotherapy.}, journal = {Tuberculosis (Edinburgh, Scotland)}, volume = {113}, number = {}, pages = {26-29}, doi = {10.1016/j.tube.2018.08.015}, pmid = {30514510}, issn = {1873-281X}, mesh = {Animals ; Antitubercular Agents/adverse effects/*therapeutic use ; Drug Therapy, Combination ; Dysbiosis ; Gastrointestinal Microbiome/*drug effects ; Host-Pathogen Interactions ; Humans ; Lung/*drug effects/microbiology ; Mycobacterium tuberculosis/*drug effects/pathogenicity ; Risk Factors ; Treatment Outcome ; Tuberculosis/diagnosis/*drug therapy/microbiology ; }, abstract = {The treatment of Mycobacterium tuberculosis infection is often viewed in isolation from other human microbial symbionts. Understandably, the clinical priority is eliminating active or latent tuberculosis (TB) in patients. With the increasing resolution of molecular biology technologies, it is becoming apparent that antibiotic treatment can perturb the homeostasis of the host microbiome. For example, dysbiosis of the gut microbiota has been associated with an increased risk of the development of asthma, obesity and diabetes. Therefore, fundamental questions include: Does TB chemotherapy cause disruption of the human microbiome and adverse effects in patients; and are there signature taxa of dysbiosis following TB treatment. In this review, we examine recent research on the detection of changes in the microbiome during antibiotic administration and discuss specific findings that relate to the impact of anti-tubercular chemotherapy.}, }
@article {pmid30510919, year = {2018}, author = {Brenner, LA and Hoisington, AJ and Stearns-Yoder, KA and Stamper, CE and Heinze, JD and Postolache, TT and Hadidi, DA and Hoffmire, CA and Stanislawski, MA and Lowry, CA}, title = {Military-Related Exposures, Social Determinants of Health, and Dysbiosis: The United States-Veteran Microbiome Project (US-VMP).}, journal = {Frontiers in cellular and infection microbiology}, volume = {8}, number = {}, pages = {400}, pmid = {30510919}, issn = {2235-2988}, abstract = {Significant effort has been put forth to increase understanding regarding the role of the human microbiome in health- and disease-related processes. In turn, the United States (US) Veteran Microbiome Project (US-VMP) was conceptualized as a means by which to serially collect microbiome and health-related data from those seeking care within the Veterans Health Administration (VHA). In this manuscript, exposures related to military experiences, as well as conditions and health-related factors among patients seen in VHA clinical settings are discussed in relation to common psychological and physical outcomes. Upon enrollment in the study, Veterans complete psychometrically sound (i.e., reliable and valid) measures regarding their past and current medical history. Participants also provide skin, oral, and gut microbiome samples, and permission to track their health status via the VHA electronic medical record. To date, data collection efforts have been cross-diagnostic. Within this manuscript, we describe current data collection practices and procedures, as well as highlight demographic, military, and psychiatric characteristics of the first 188 Veterans enrolled in the study. Based on these findings, we assert that this cohort is unique as compared to those enrolled in recent large-scale studies of the microbiome. To increase understanding regarding disease and health among diverse cohorts, efforts such as the US-VMP are vital. Ongoing barriers and facilitators to data collection are discussed, as well as future research directions, with an emphasis on the importance of shifting current thinking regarding the microbiome from a focus on normalcy and dysbiosis to health promotion and disease prevention.}, }
@article {pmid30510497, year = {2018}, author = {Mathias, M}, title = {Autointoxication and historical precursors of the microbiome-gut-brain axis.}, journal = {Microbial ecology in health and disease}, volume = {29}, number = {2}, pages = {1548249}, pmid = {30510497}, issn = {0891-060X}, abstract = {This article focuses on autointoxication, a discredited medical theory from the late nineteenth century that provides important points of reflection for today's research on the role of microbes in the human gut for mental health. It considers how the theory of autointoxication, which came into great prominence amongst physicians and the general public worldwide, fell from grace by the middle of the twentieth century, and briefly asks why studies of the human microbiome are now back in vogue. It departs from earlier articles on the topic firstly by arguing that autointoxication theory was especially prevalent in France, and secondly by focusing on the application of this theory to mental health. Bringing to light medical treatises and theses from this period which have so far remained unexamined, it shows that examining the development and reception of medical theories form the past can help us today in understanding both the pitfalls and promise of research in this area.}, }
@article {pmid30487377, year = {2018}, author = {Ando, H}, title = {[Creation of synthetic bacterial viruses].}, journal = {Nihon saikingaku zasshi. Japanese journal of bacteriology}, volume = {73}, number = {4}, pages = {201-210}, doi = {10.3412/jsb.73.201}, pmid = {30487377}, issn = {1882-4110}, mesh = {Bacteria/*virology ; Bacterial Infections/*therapy ; *Bacteriophages/genetics ; Drug Resistance, Bacterial ; *Genetic Engineering/methods ; *Genome, Viral/genetics ; Host Specificity ; Humans ; *Phage Therapy ; Polymerase Chain Reaction ; }, abstract = {Bacteria are closely related with human health and diseases. For example, the emergence of drug-resistant bacteria is a serious problem in the world. Studying the human microbiome shows its important role for our health. But we have very limited tools to edit bacterial population. Antibiotics are generally broad-spectrum and unable to kill only bad bacteria. The natural enemies of bacteria, called bacteriophage (phage), have highly specific host range, and thus promising candidates for targeted bacterial population editing. However, isolation and characterization of natural phages can be a time-, labor- and cost-intensive way. Also, developing phage-based therapeutics and diagnostics is limited by the difficulty of engineering phages. Here, I describe a phage genome-engineering platform and synthetic phages with tunable host ranges to overcome these challenges.}, }
@article {pmid30482830, year = {2018}, author = {Espinoza, JL and Harkins, DM and Torralba, M and Gomez, A and Highlander, SK and Jones, MB and Leong, P and Saffery, R and Bockmann, M and Kuelbs, C and Inman, JM and Hughes, T and Craig, JM and Nelson, KE and Dupont, CL}, title = {Supragingival Plaque Microbiome Ecology and Functional Potential in the Context of Health and Disease.}, journal = {mBio}, volume = {9}, number = {6}, pages = {}, pmid = {30482830}, issn = {2150-7511}, support = {R01 DE019665/DE/NIDCR NIH HHS/United States ; R01 GM120624/GM/NIGMS NIH HHS/United States ; }, mesh = {Australia ; Bacteria/*classification/*genetics ; Child ; Child, Preschool ; Dental Caries/*microbiology ; Dental Plaque/*microbiology ; Humans ; Metabolic Networks and Pathways/genetics ; Metagenomics ; *Microbiota ; Sequence Analysis, DNA ; }, abstract = {To address the question of how microbial diversity and function in the oral cavities of children relates to caries diagnosis, we surveyed the supragingival plaque biofilm microbiome in 44 juvenile twin pairs. Using shotgun sequencing, we constructed a genome encyclopedia describing the core supragingival plaque microbiome. Caries phenotypes contained statistically significant enrichments in specific genome abundances and distinct community composition profiles, including strain-level changes. Metabolic pathways that are statistically associated with caries include several sugar-associated phosphotransferase systems, antimicrobial resistance, and metal transport. Numerous closely related previously uncharacterized microbes had substantial variation in central metabolism, including the loss of biosynthetic pathways resulting in auxotrophy, changing the ecological role. We also describe the first complete Gracilibacteria genomes from the human microbiome. Caries is a microbial community metabolic disorder that cannot be described by a single etiology, and our results provide the information needed for next-generation diagnostic tools and therapeutics for caries.IMPORTANCE Oral health has substantial economic importance, with over $100 billion spent on dental care in the United States annually. The microbiome plays a critical role in oral health, yet remains poorly classified. To address the question of how microbial diversity and function in the oral cavities of children relate to caries diagnosis, we surveyed the supragingival plaque biofilm microbiome in 44 juvenile twin pairs. Using shotgun sequencing, we constructed a genome encyclopedia describing the core supragingival plaque microbiome. This unveiled several new previously uncharacterized but ubiquitous microbial lineages in the oral microbiome. Caries is a microbial community metabolic disorder that cannot be described by a single etiology, and our results provide the information needed for next-generation diagnostic tools and therapeutics for caries.}, }
@article {pmid30481125, year = {2018}, author = {Kim, JW and Lee, JS and Kim, JH and Jeong, JW and Lee, DH and Nam, S}, title = {Comparison of Microbiota Variation in Korean Healthy Adolescents with Adults Suggests Notable Maturity Differences.}, journal = {Omics : a journal of integrative biology}, volume = {22}, number = {12}, pages = {770-778}, doi = {10.1089/omi.2018.0146}, pmid = {30481125}, issn = {1557-8100}, mesh = {Adolescent ; Gastrointestinal Microbiome/*genetics ; Humans ; Microbiota/*genetics ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, RNA/methods ; }, abstract = {Comparative studies of microbiome variation in world populations and different developmental stages of organisms are essential to decipher the linkages among microbiome, health, and disease. Notably, the gut microbiota are believed to mature in early life. In this context, we compared the gut microbiota diversity in Korean adolescent healthy samples (KAHSs) to healthy Korean adults (HKAs) as well as the Human Microbiome Project healthy samples (HMPHSs), the latter being one of the largest adult cohorts, based on organismal composition, alpha- and beta-diversities, function/pathway prediction analysis, and co-occurrence networks. We found that the gut microbiota compositions, including the ratios of firmicutes to bacteroidetes, between KAHSs and HMPHSs were different, and the diversities of KAHSs were less than those of HMPHSs. The predicted functions, for example, secondary bile acid synthesis and insulin signaling of KAHSs and HMPHSs, were also significantly different. Genus-level networks showed that co-occurrences among different taxa more frequently happened in HMPHSs than in KAHSs. Even though both KAHSs and HMPHSs represent healthy microbiomes, comparisons showed substantial differences, likely implicating different diets, environments, and demographics. Interestingly, we observed lower microbial diversities and less frequent co-occurrences among different taxa in KAHSs than adult HMPHSs and HKAs. These new findings collectively suggest that the adolescent gut microbiota in the present Korean sample did not reach the extent of maturity of adult microbiota diversity. In all, further population studies of microbiome variation across geographies and developmental stages are warranted, and should usefully inform future diagnostics and therapeutics innovation targeting the microbiome.}, }
@article {pmid30477563, year = {2018}, author = {Sinha, R and Ahsan, H and Blaser, M and Caporaso, JG and Carmical, JR and Chan, AT and Fodor, A and Gail, MH and Harris, CC and Helzlsouer, K and Huttenhower, C and Knight, R and Kong, HH and Lai, GY and Hutchinson, DLS and Le Marchand, L and Li, H and Orlich, MJ and Shi, J and Truelove, A and Verma, M and Vogtmann, E and White, O and Willett, W and Zheng, W and Mahabir, S and Abnet, C}, title = {Next steps in studying the human microbiome and health in prospective studies, Bethesda, MD, May 16-17, 2017.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {210}, pmid = {30477563}, issn = {2049-2618}, mesh = {Computational Biology/*methods ; Humans ; Microbiota/*physiology ; Neoplasms/*etiology ; Prospective Studies ; Reproducibility of Results ; *Research Design ; }, abstract = {The National Cancer Institute (NCI) sponsored a 2-day workshop, &quot;Next Steps in Studying the Human Microbiome and Health in Prospective Studies,&quot; in Bethesda, Maryland, May 16-17, 2017. The workshop brought together researchers in the field to discuss the challenges of conducting microbiome studies, including study design, collection and processing of samples, bioinformatics and statistical methods, publishing results, and ensuring reproducibility of published results. The presenters emphasized the great potential of microbiome research in understanding the etiology of cancer. This report summarizes the workshop and presents practical suggestions for conducting microbiome studies, from workshop presenters, moderators, and participants.}, }
@article {pmid30477107, year = {2018}, author = {Cristofori, F and Indrio, F and Miniello, VL and De Angelis, M and Francavilla, R}, title = {Probiotics in Celiac Disease.}, journal = {Nutrients}, volume = {10}, number = {12}, pages = {}, doi = {10.3390/nu10121824}, pmid = {30477107}, issn = {2072-6643}, mesh = {Animals ; Bacteria/*growth &amp; development ; Celiac Disease/*drug therapy/microbiology ; *Diet, Gluten-Free ; *Dysbiosis/complications/drug therapy ; *Gastrointestinal Microbiome ; Humans ; Probiotics/*therapeutic use ; }, abstract = {Recently, the interest in the human microbiome and its interplay with the host has exploded and provided new insights on its role in conferring host protection and regulating host physiology, including the correct development of immunity. However, in the presence of microbial imbalance and particular genetic settings, the microbiome may contribute to the dysfunction of host metabolism and physiology, leading to pathogenesis and/or the progression of several diseases. Celiac disease (CD) is a chronic autoimmune enteropathy triggered by dietary gluten exposure in genetically predisposed individuals. Despite ascertaining that gluten is the trigger in CD, evidence has indicated that intestinal microbiota is somehow involved in the pathogenesis, progression, and clinical presentation of CD. Indeed, several studies have reported imbalances in the intestinal microbiota of patients with CD that are mainly characterized by an increased abundance of Bacteroides spp. and a decrease in Bifidobacterium spp. The evidence that some of these microbial imbalances still persist in spite of a strict gluten-free diet and that celiac patients suffering from persistent gastrointestinal symptoms have a desert gut microbiota composition further support its close link with CD. All of this evidence gives rise to the hypothesis that probiotics might play a role in this condition. In this review, we describe the recent scientific evidences linking the gut microbiota in CD, starting from the possible role of microbes in CD pathogenesis, the attempt to define a microbial signature of disease, the effect of a gluten-free diet and host genetic assets regarding microbial composition to end in the exploration of the proof of concept of probiotic use in animal models to the most recent clinical application of selected probiotic strains.}, }
@article {pmid30474490, year = {2018}, author = {Jonsson, V and Österlund, T and Nerman, O and Kristiansson, E}, title = {Modelling of zero-inflation improves inference of metagenomic gene count data.}, journal = {Statistical methods in medical research}, volume = {}, number = {}, pages = {962280218811354}, doi = {10.1177/0962280218811354}, pmid = {30474490}, issn = {1477-0334}, abstract = {Metagenomics enables the study of gene abundances in complex mixtures of microorganisms and has become a standard methodology for the analysis of the human microbiome. However, gene abundance data is inherently noisy and contains high levels of biological and technical variability as well as an excess of zeros due to non-detected genes. This makes the statistical analysis challenging. In this study, we present a new hierarchical Bayesian model for inference of metagenomic gene abundance data. The model uses a zero-inflated overdispersed Poisson distribution which is able to simultaneously capture the high gene-specific variability as well as zero observations in the data. By analysis of three comprehensive datasets, we show that zero-inflation is common in metagenomic data from the human gut and, if not correctly modelled, it can lead to substantial reductions in statistical power. We also show, by using resampled metagenomic data, that our model has, compared to other methods, a higher and more stable performance for detecting differentially abundant genes. We conclude that proper modelling of the gene-specific variability, including the excess of zeros, is necessary to accurately describe gene abundances in metagenomic data. The proposed model will thus pave the way for new biological insights into the structure of microbial communities.}, }
@article {pmid30466159, year = {2019}, author = {Mendez, R and Banerjee, S and Bhattacharya, SK and Banerjee, S}, title = {Lung inflammation and disease: A perspective on microbial homeostasis and metabolism.}, journal = {IUBMB life}, volume = {71}, number = {2}, pages = {152-165}, doi = {10.1002/iub.1969}, pmid = {30466159}, issn = {1521-6551}, support = {P30 EY014801/NEI NIH HHS/National Eye Institute/United States ; R21 HL125021/NHLBI NIH HHS/National Heart, Lung, and Blood Institute/United States ; }, abstract = {It is now well appreciated that the human microbiome plays a significant role in a number of processes in the body, significantly affecting its metabolic, inflammatory, and immune homeostasis. Recent research has revealed that almost every mucosal surface in the human body is associated with a resident commensal microbiome of its own. While the gut microbiome and its role in regulation of host metabolism along with its alteration in a disease state has been well studied, there is a lacuna in understanding the resident microbiota of other mucosal surfaces. Among these, the scientific information on the role of lung microbiota in pulmonary diseases is currently severely limited. Historically, lungs have been considered to be sterile and lung diseases have only been studied in the context of bacterial pathogenesis. Recently however, studies have revealed a resilient microbiome in the upper and lower respiratory tracts and there is increased evidence on its central role in respiratory diseases. Knowledge of lung microbiome and its metabolic fallout (local and systemic) is still in its nascent stages and attracting immense interest in recent times. In this review, we will provide a perspective on lung-associated metabolic disorders defined for lung diseases (e.g., chronic obstructive pulmonary disease, asthma, and respiratory depression due to infection) and correlate it with lung microbial perturbation. Such perturbations may be due to altered biochemical or metabolic stress as well. Finally, we will draw evidence from microbiome and classical microbiology literature to demonstrate how specific lung morbidities associate with specific metabolic characteristics of the disease, and with the role of microbiome in this context. © 2018 IUBMB Life, 71(1):152-165, 2019.}, }
@article {pmid30466152, year = {2019}, author = {Beilsmith, K and Thoen, MPM and Brachi, B and Gloss, AD and Khan, MH and Bergelson, J}, title = {Genome-wide association studies on the phyllosphere microbiome: Embracing complexity in host-microbe interactions.}, journal = {The Plant journal : for cell and molecular biology}, volume = {97}, number = {1}, pages = {164-181}, doi = {10.1111/tpj.14170}, pmid = {30466152}, issn = {1365-313X}, support = {//University of Chicago Biological Sciences Division/ ; //Dropkin Foundation/ ; }, abstract = {Environmental sequencing shows that plants harbor complex communities of microbes that vary across environments. However, many approaches for mapping plant genetic variation to microbe-related traits were developed in the relatively simple context of binary host-microbe interactions under controlled conditions. Recent advances in sequencing and statistics make genome-wide association studies (GWAS) an increasingly promising approach for identifying the plant genetic variation associated with microbes in a community context. This review discusses early efforts on GWAS of the plant phyllosphere microbiome and the outlook for future studies based on human microbiome GWAS. A workflow for GWAS of the phyllosphere microbiome is then presented, with particular attention to how perspectives on the mechanisms, evolution and environmental dependence of plant-microbe interactions will influence the choice of traits to be mapped.}, }
@article {pmid30465353, year = {2018}, author = {Wang, H and Kang, D and Zhou, XD and Li, YQ}, title = {[Prevention of infectious diseases through microecology modulation techniques].}, journal = {Hua xi kou qiang yi xue za zhi = Huaxi kouqiang yixue zazhi = West China journal of stomatology}, volume = {36}, number = {5}, pages = {564-567}, doi = {10.7518/hxkq.2018.05.018}, pmid = {30465353}, issn = {2618-0456}, mesh = {Humans ; *Microbiota ; Mouth/microbiology ; Skin/microbiology ; }, abstract = {The microbe is small in volume, but large in quantity and species. The symbiotic microbe, which is far more than human cells, code millions times of genes than human being. Somatic cells and these symbiotic microbe distributing in human body skin, respiratory tract, oral cavity and gastrointestinal tract, urinary tract and other parts form a complex ecosystem whose dynamic balance is highly related to body health. With the successful implementation of Human Microbiome Project, more attentions have been paid to the next generation microbiome technologies. New tools and methods for ecological regulation of human microbiome are emerging. The way we improve the world of human microbiology will be more convenient. This paper will make a review on the modulation techniques of human microbiome.}, }
@article {pmid30460770, year = {2018}, author = {Barbara, G and Cremon, C and Azpiroz, F}, title = {Probiotics in irritable bowel syndrome: Where are we?.}, journal = {Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society}, volume = {30}, number = {12}, pages = {e13513}, doi = {10.1111/nmo.13513}, pmid = {30460770}, issn = {1365-2982}, support = {SAF 2016-76648-R//Italian Ministry of Education, University and Research, and the Spanish Ministry of Economy and Competitiveness/International ; //Instituto de Salud Carlos III/International ; //University of Bologna RFO/International ; //Fondazione del Monte di Bologna e Ravenna/International ; }, abstract = {We have only recently begun to understand how alterations of the intestinal microbial ecosystem lead to the disruption of host-microbial interactions and are associated with diseases, including functional gastrointestinal disorders such as irritable bowel syndrome (IBS). Although we are still far from understanding the human microbiome, gut microbiota is already a therapeutic target. Probiotics are live microorganisms that, when administered in adequate amounts, confer a health benefit to the host and may represent a therapeutic option for diseases characterized by dysbiosis such as IBS. Meta-analyses suggest that probiotics provide a therapeutic gain over placebo on global symptoms with a high safety profile in IBS patients. However, the mechanisms by which they provide benefit in IBS remain virtually unknown. In this issue of Neurogastroenterology and Motility, BIO-25, a multispecies probiotic, did not significantly modify the composition of the fecal microbiota, but interestingly, patients with specific basal features of the intestinal microbial ecosystem improved with treatment. Based on these data, it is tantalizing to speculate that microbiota composition serves as a predictor of the response to probiotic intervention. This mini-review addresses unresolved issues related to mechanisms through which probiotics may exert their beneficial effects, the biological, as well as clinical predictors of favorable outcomes in IBS and finally considers possible new directions for future studies.}, }
@article {pmid30459400, year = {2018}, author = {Chen, B and Zhao, Y and Li, S and Yang, L and Wang, H and Wang, T and Bin Shi,  and Gai, Z and Heng, X and Zhang, C and Yang, J and Zhang, L}, title = {Variations in oral microbiome profiles in rheumatoid arthritis and osteoarthritis with potential biomarkers for arthritis screening.}, journal = {Scientific reports}, volume = {8}, number = {1}, pages = {17126}, pmid = {30459400}, issn = {2045-2322}, support = {No. 31471202//National Natural Science Foundation of China (National Science Foundation of China)/ ; }, abstract = {The key to arthritis management is early diagnosis and treatment to prevent further joint destruction and maximize functional ability. Osteoarthritis (OA) and rheumatoid arthritis (RA) are two common types of arthritis that the primary care provider must differentiate, in terms of diagnosis and treatment. Effective and non-invasive strategies for early detection and disease identification are sorely needed. Growing evidence suggests that RA has a correlation with oral microbiome and may be affected by its dynamic variations. There is already a study comparing oral microbiome in patients with RA and OA, however, it did not screen for potential biomarkers for arthritis. In this study, we assessed the oral microbiome in saliva samples from 110 RA patients, 67 OA patients and 155 healthy subjects, using 16S rRNA gene amplicon sequencing. The structure and differences in oral microbiome between RA, OA and healthy subjects were analyzed. Eight oral bacterial biomarkers were identified to differentiate RA from OA. This report provides proof of oral microbiota as an informative source for discovering non-invasive biomarkers for arthritis screening.}, }
@article {pmid30452039, year = {2019}, author = {Rajakovich, LJ and Balskus, EP}, title = {Metabolic functions of the human gut microbiota: the role of metalloenzymes.}, journal = {Natural product reports}, volume = {36}, number = {4}, pages = {593-625}, doi = {10.1039/c8np00074c}, pmid = {30452039}, issn = {1460-4752}, abstract = {Covering: up to the end of 2017 The human body is composed of an equal number of human and microbial cells. While the microbial community inhabiting the human gastrointestinal tract plays an essential role in host health, these organisms have also been connected to various diseases. Yet, the gut microbial functions that modulate host biology are not well established. In this review, we describe metabolic functions of the human gut microbiota that involve metalloenzymes. These activities enable gut microbial colonization, mediate interactions with the host, and impact human health and disease. We highlight cases in which enzyme characterization has advanced our understanding of the gut microbiota and examples that illustrate the diverse ways in which metalloenzymes facilitate both essential and unique functions of this community. Finally, we analyze Human Microbiome Project sequencing datasets to assess the distribution of a prominent family of metalloenzymes in human-associated microbial communities, guiding future enzyme characterization efforts.}, }
@article {pmid30449316, year = {2018}, author = {Guerin, E and Shkoporov, A and Stockdale, SR and Clooney, AG and Ryan, FJ and Sutton, TDS and Draper, LA and Gonzalez-Tortuero, E and Ross, RP and Hill, C}, title = {Biology and Taxonomy of crAss-like Bacteriophages, the Most Abundant Virus in the Human Gut.}, journal = {Cell host &amp; microbe}, volume = {24}, number = {5}, pages = {653-664.e6}, doi = {10.1016/j.chom.2018.10.002}, pmid = {30449316}, issn = {1934-6069}, mesh = {Bacteriophages/*classification/*genetics/*physiology/ultrastructure ; Base Sequence ; Capsid Proteins/genetics ; DNA Viruses ; Feces/virology ; Fermentation ; *Gastrointestinal Microbiome ; Genome, Viral/genetics ; Genomics ; Humans ; Metagenomics/methods ; *Phylogeny ; Sequence Analysis ; Viral Proteins/genetics ; }, abstract = {CrAssphages represent the most abundant virus in the human gut microbiota, but the lack of available genome sequences for comparison has kept them enigmatic. Recently, sequence-based classification of distantly related crAss-like phages from multiple environments was reported, leading to a proposed familial-level taxonomic group. Here, we assembled the metagenomic sequencing reads from 702 human fecal virome/phageome samples and analyzed 99 complete circular crAss-like phage genomes and 150 contigs ≥70 kb. In silico comparative genomics and taxonomic analysis enabled a classification scheme of crAss-like phages from human fecal microbiomes into four candidate subfamilies composed of ten candidate genera. Laboratory analysis was performed on fecal samples from an individual harboring seven distinct crAss-like phages. We achieved crAss-like phage propagation in ex vivo human fecal fermentations and visualized short-tailed podoviruses by electron microscopy. Mass spectrometry of a crAss-like phage capsid protein could be linked to metagenomic sequencing data, confirming crAss-like phage structural annotations.}, }
@article {pmid30443602, year = {2018}, author = {Hillmann, B and Al-Ghalith, GA and Shields-Cutler, RR and Zhu, Q and Gohl, DM and Beckman, KB and Knight, R and Knights, D}, title = {Evaluating the Information Content of Shallow Shotgun Metagenomics.}, journal = {mSystems}, volume = {3}, number = {6}, pages = {}, pmid = {30443602}, issn = {2379-5077}, support = {P01 DK078669/DK/NIDDK NIH HHS/United States ; R01 AI121383/AI/NIAID NIH HHS/United States ; }, abstract = {Although microbial communities are associated with human, environmental, plant, and animal health, there exists no cost-effective method for precisely characterizing species and genes in such communities. While deep whole-metagenome shotgun (WMS) sequencing provides high taxonomic and functional resolution, it is often prohibitively expensive for large-scale studies. The prevailing alternative, 16S rRNA gene amplicon (16S) sequencing, often does not resolve taxonomy past the genus level and provides only moderately accurate predictions of the functional profile; thus, there is currently no widely accepted approach to affordable, high-resolution, taxonomic, and functional microbiome analysis. To address this technology gap, we evaluated the information content of shallow shotgun sequencing with as low as 0.5 million sequences per sample as an alternative to 16S sequencing for large human microbiome studies. We describe a library preparation protocol enabling shallow shotgun sequencing at approximately the same per-sample cost as 16S sequencing. We analyzed multiple real and simulated biological data sets, including two novel human stool samples with ultradeep sequencing of 2.5 billion sequences per sample, and found that shallow shotgun sequencing recovers more-accurate species-level taxonomic and functional profiles of the human microbiome than 16S sequencing. We discuss the inherent limitations of shallow shotgun sequencing and note that 16S sequencing remains a valuable and important method for taxonomic profiling of novel environments. Although deep WMS sequencing remains the gold standard for high-resolution microbiome analysis, we recommend that researchers consider shallow shotgun sequencing as a useful alternative to 16S sequencing for large-scale human microbiome research studies where WMS sequencing may be cost-prohibitive. IMPORTANCE A common refrain in recent microbiome-related academic meetings is that the field needs to move away from broad taxonomic surveys using 16S sequencing and toward more powerful longitudinal studies using shotgun sequencing. However, performing deep shotgun sequencing in large longitudinal studies remains prohibitively expensive for all but the most well-funded research labs and consortia, which leads many researchers to choose 16S sequencing for large studies, followed by deep shotgun sequencing on a subset of targeted samples. Here, we show that shallow- or moderate-depth shotgun sequencing may be used by researchers to obtain species-level taxonomic and functional data at approximately the same cost as amplicon sequencing. While shallow shotgun sequencing is not intended to replace deep shotgun sequencing for strain-level characterization, we recommend that microbiome scientists consider using shallow shotgun sequencing instead of 16S sequencing for large-scale human microbiome studies.}, }
@article {pmid30439937, year = {2018}, author = {Jha, AR and Davenport, ER and Gautam, Y and Bhandari, D and Tandukar, S and Ng, KM and Fragiadakis, GK and Holmes, S and Gautam, GP and Leach, J and Sherchand, JB and Bustamante, CD and Sonnenburg, JL}, title = {Gut microbiome transition across a lifestyle gradient in Himalaya.}, journal = {PLoS biology}, volume = {16}, number = {11}, pages = {e2005396}, pmid = {30439937}, issn = {1545-7885}, support = {R01 DK085025/DK/NIDDK NIH HHS/United States ; }, mesh = {Adult ; Bacteria/genetics ; Diet ; Diet, Paleolithic ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*genetics/physiology ; Genetics, Population/methods ; Geography ; Humans ; Life Style/*ethnology ; Male ; Microbiota/*genetics ; Middle Aged ; Nepal/ethnology ; RNA, Ribosomal, 16S/genetics ; Rural Population ; }, abstract = {The composition of the gut microbiome in industrialized populations differs from those living traditional lifestyles. However, it has been difficult to separate the contributions of human genetic and geographic factors from lifestyle. Whether shifts away from the foraging lifestyle that characterize much of humanity's past influence the gut microbiome, and to what degree, remains unclear. Here, we characterize the stool bacterial composition of four Himalayan populations to investigate how the gut community changes in response to shifts in traditional human lifestyles. These groups led seminomadic hunting-gathering lifestyles until transitioning to varying levels of agricultural dependence upon farming. The Tharu began farming 250-300 years ago, the Raute and Raji transitioned 30-40 years ago, and the Chepang retain many aspects of a foraging lifestyle. We assess the contributions of dietary and environmental factors on their gut-associated microbes and find that differences in the lifestyles of Himalayan foragers and farmers are strongly correlated with microbial community variation. Furthermore, the gut microbiomes of all four traditional Himalayan populations are distinct from that of the Americans, indicating that industrialization may further exacerbate differences in the gut community. The Chepang foragers harbor an elevated abundance of taxa associated with foragers around the world. Conversely, the gut microbiomes of the populations that have transitioned to farming are more similar to those of Americans, with agricultural dependence and several associated lifestyle and environmental factors correlating with the extent of microbiome divergence from the foraging population. The gut microbiomes of Raute and Raji reveal an intermediate state between the Chepang and Tharu, indicating that divergence from a stereotypical foraging microbiome can occur within a single generation. Our results also show that environmental factors such as drinking water source and solid cooking fuel are significantly associated with the gut microbiome. Despite the pronounced differences in gut bacterial composition across populations, we found little differences in alpha diversity across lifestyles. These findings in genetically similar populations living in the same geographical region establish the key role of lifestyle in determining human gut microbiome composition and point to the next challenging steps of determining how large-scale gut microbiome reconfiguration impacts human biology.}, }
@article {pmid30431239, year = {2019}, author = {Berry, D}, title = {Up-close-and-personal with the human microbiome.}, journal = {Environmental microbiology reports}, volume = {11}, number = {1}, pages = {17-19}, doi = {10.1111/1758-2229.12709}, pmid = {30431239}, issn = {1758-2229}, mesh = {Diet Therapy ; Drug Design ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/drug effects/genetics/*physiology ; Genomics ; Humans ; Microbiota/drug effects/genetics/*physiology ; Phage Therapy ; }, }
@article {pmid30426826, year = {2019}, author = {Daisley, BA and Monachese, M and Trinder, M and Bisanz, JE and Chmiel, JA and Burton, JP and Reid, G}, title = {Immobilization of cadmium and lead by Lactobacillus rhamnosus GR-1 mitigates apical-to-basolateral heavy metal translocation in a Caco-2 model of the intestinal epithelium.}, journal = {Gut microbes}, volume = {10}, number = {3}, pages = {321-333}, doi = {10.1080/19490976.2018.1526581}, pmid = {30426826}, issn = {1949-0984}, abstract = {Heavy metals are highly toxic elements that contaminate the global food supply and affect human and wildlife health. Purification technologies are often too expensive or not practically applicable for large-scale implementation, especially in impoverished nations where heavy metal contamination is widespread. Lactobacillus rhamnosus GR-1 (LGR-1) was shown in previous work to reduce heavy metal bioaccumulation in a Tanzanian cohort of women and children through indeterminant mechanisms. Here, it was hypothesized that LGR-1 could sequester the heavy metals lead (Pb) and cadmium (Cd), thereby reducing their absorption across intestinal epithelium. LGR-1 and other lactobacilli significantly reduced the amount of Pb and Cd in solution at all concentrations tested (0.5 mg/L - 50 mg/L) and exhibited sustained binding profiles over a 48-hour period. Relative binding efficiency of LGR-1 decreased as Pb concentration increased, with an absolute minimum binding threshold apparent at concentrations of 2 mg/L and above. Electron microscopy revealed that Pb formed irregular cell-surface clusters on LGR-1, while Cd appeared to form intracellular polymeric clusters. Additionally, LGR-1 was able to significantly reduce apical-to-basolateral translocation of Pb and Cd in a Caco-2 model of the intestinal epithelium. These findings demonstrate the absorbent properties of LGR-1 can immobilize Pb and Cd, effectively reducing their translocation across the intestinal epithelium in vitro. Oral administration of heavy metal-binding Lactobacillus spp. (many of which are known human symbionts and strains of established probiotics) may offer a simple and effective means to reduce the amount of heavy metals absorbed from foods in contaminated regions of the world.}, }
@article {pmid30423063, year = {2018}, author = {Frioux, C and Fremy, E and Trottier, C and Siegel, A}, title = {Scalable and exhaustive screening of metabolic functions carried out by microbial consortia.}, journal = {Bioinformatics (Oxford, England)}, volume = {34}, number = {17}, pages = {i934-i943}, pmid = {30423063}, issn = {1367-4811}, abstract = {Motivation: The selection of species exhibiting metabolic behaviors of interest is a challenging step when switching from the investigation of a large microbiota to the study of functions effectiveness. Approaches based on a compartmentalized framework are not scalable. The output of scalable approaches based on a non-compartmentalized modeling may be so large that it has neither been explored nor handled so far.<br><br>Results: We present the Miscoto tool to facilitate the selection of a community optimizing a desired function in a microbiome by reporting several possibilities which can be then sorted according to biological criteria. Communities are exhaustively identified using logical programming and by combining the non-compartmentalized and the compartmentalized frameworks. The benchmarking of 4.9 million metabolic functions associated with the Human Microbiome Project, shows that Miscoto is suited to screen and classify metabolic producibility in terms of feasibility, functional redundancy and cooperation processes involved. As an illustration of a host-microbial system, screening the Recon 2.2 human metabolism highlights the role of different consortia within a family of 773 intestinal bacteria.<br><br>Miscoto source code, instructions for use and examples are available at: https://github.com/cfrioux/miscoto.}, }
@article {pmid30420594, year = {2018}, author = {Yost, S and Stashenko, P and Choi, Y and Kukuruzinska, M and Genco, CA and Salama, A and Weinberg, EO and Kramer, CD and Frias-Lopez, J}, title = {Increased virulence of the oral microbiome in oral squamous cell carcinoma revealed by metatranscriptome analyses.}, journal = {International journal of oral science}, volume = {10}, number = {4}, pages = {32}, pmid = {30420594}, issn = {2049-3169}, mesh = {Carcinoma, Squamous Cell/*microbiology ; Humans ; *Metagenome ; *Microbiota ; Mouth Neoplasms/*microbiology ; Phylogeny ; Pilot Projects ; RNA, Messenger/metabolism ; *Transcriptome ; Virulence ; Virulence Factors/*metabolism ; }, abstract = {Oral squamous cell carcinoma (OSCC) is the most prevalent and most commonly studied oral cancer. However, there is a void regarding the role that the oral microbiome may play in OSCC. Although the relationship between microbial community composition and OSCC has been thoroughly investigated, microbial profiles of the human microbiome in cancer are understudied. Here we performed a small pilot study of community-wide metatranscriptome analysis to profile mRNA expression in the entire oral microbiome in OSCC to reveal molecular functions associated with this disease. Fusobacteria showed a statistically significantly higher number of transcripts at tumour sites and tumour-adjacent sites of cancer patients compared to the healthy controls analysed. Regardless of the community composition, specific metabolic signatures were consistently found in disease. Activities such as iron ion transport, tryptophanase activity, peptidase activities and superoxide dismutase were over-represented in tumour and tumour-adjacent samples when compared to the healthy controls. The expression of putative virulence factors in the oral communities associated with OSCC showed that activities related to capsule biosynthesis, flagellum synthesis and assembly, chemotaxis, iron transport, haemolysins and adhesins were upregulated at tumour sites. Moreover, activities associated with protection against reactive nitrogen intermediates, chemotaxis, flagellar and capsule biosynthesis were also upregulated in non-tumour sites of cancer patients. Although they are preliminary, our results further suggest that Fusobacteria may be the leading phylogenetic group responsible for the increase in expression of virulence factors in the oral microbiome of OSCC patients.}, }
@article {pmid30419494, year = {2019}, author = {Ventura Spagnolo, E and Stassi, C and Mondello, C and Zerbo, S and Milone, L and Argo, A}, title = {Forensic microbiology applications: A systematic review.}, journal = {Legal medicine (Tokyo, Japan)}, volume = {36}, number = {}, pages = {73-80}, doi = {10.1016/j.legalmed.2018.11.002}, pmid = {30419494}, issn = {1873-4162}, mesh = {Adult ; Aged ; Body Fluids/*microbiology ; Brain/*microbiology ; Cause of Death ; Databases, Bibliographic ; Digestive System/*microbiology ; Female ; *Forensic Medicine ; Heart/*microbiology ; Humans ; Male ; *Microbiota ; Middle Aged ; *Postmortem Changes ; Skin/*microbiology ; Time Factors ; }, abstract = {According to the Human Microbiome Project (HMP), a healthy human body contains ten times more microbes than human cells. Microbial communities colonize different organs of the body, playing fundamental roles both in human health and disease. Despite the vast scientific knowledge of the role of microbial communities in a living body, little is known at present about microbial changes occurring after death, thus leading many authors to investigate the composition of the thanatomicrobiome and its potential applications in the forensic field. The aim of the following review is to provide a general overview of the advances of postmortem microbiology research, mainly focusing on the role of microbiological investigations carried out on internal organs and fluids. To this end, a total of 19 studies have been sistematically reviewed, each one chosen according to specific inclusion/exclusion criteria. The selected studies assess the contribution of contamination, postmortem transmigration and agonal spread to microbial isolation from dead body samples, and shed light on the role of postmortem microbiological investigations in several forensic fields, such as cause of death or PMI determination.}, }
@article {pmid30417656, year = {2018}, author = {Fonkou, MD and Dufour, JC and Dubourg, G and Raoult, D}, title = {Repertoire of bacterial species cultured from the human oral cavity and respiratory tract.}, journal = {Future microbiology}, volume = {13}, number = {}, pages = {1611-1624}, doi = {10.2217/fmb-2018-0181}, pmid = {30417656}, issn = {1746-0921}, mesh = {Bacteria/*genetics/*pathogenicity ; Bronchoalveolar Lavage Fluid/microbiology ; Cell Culture Techniques ; High-Throughput Nucleotide Sequencing ; Humans ; Lung/microbiology ; MEDLINE ; Microbiota/*genetics ; Mouth/*microbiology ; Respiratory System/*microbiology ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; Sputum/microbiology ; Virulence/genetics ; }, abstract = {While the gut microbiota is currently in the spotlight, the airway microbiome has been recently associated with several pulmonary diseases and carcinogenesis. As there are several biases associated with high-throughput sequencing methods, cultivation techniques are crucial for the investigation of the human microbiome. We thus aimed to build an exhaustive database, including a list of microbes isolated by culture from respiratory specimens, by performing a review of the literature. Herein, we have listed a total of 756 species cultured from the human respiratory tract. This represents 27.23% of the overall bacterial richness captured from human being by culture methods. This repertoire could be valuable for the elucidation of the interactions between the respiratory microbiome and human health.}, }
@article {pmid30401779, year = {2018}, author = {Bratburd, JR and Keller, C and Vivas, E and Gemperline, E and Li, L and Rey, FE and Currie, CR}, title = {Gut Microbial and Metabolic Responses to Salmonella enterica Serovar Typhimurium and Candida albicans.}, journal = {mBio}, volume = {9}, number = {6}, pages = {}, pmid = {30401779}, issn = {2150-7511}, support = {U19 AI109673/AI/NIAID NIH HHS/United States ; R56 DK071801/DK/NIDDK NIH HHS/United States ; R01 DK108259/DK/NIDDK NIH HHS/United States ; S10 RR029531/RR/NCRR NIH HHS/United States ; T32 AI055397/AI/NIAID NIH HHS/United States ; R01 DK071801/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Biosynthetic Pathways ; Candida albicans/pathogenicity ; Candidiasis/*microbiology ; Cecum/microbiology ; Disease Models, Animal ; Enterobacteriaceae/isolation &amp; purification ; *Gastrointestinal Microbiome ; Germ-Free Life ; Humans ; Male ; Metabolomics ; Metagenomics ; Mice ; Mice, Inbred C57BL ; *Microbiota ; Oxidative Stress ; Salmonella Infections, Animal/*microbiology ; Salmonella typhimurium/pathogenicity ; }, abstract = {The gut microbiota confers resistance to pathogens of the intestinal ecosystem, yet the dynamics of pathogen-microbiome interactions and the metabolites involved in this process remain largely unknown. Here, we use gnotobiotic mice infected with the virulent pathogen Salmonella enterica serovar Typhimurium or the opportunistic pathogen Candida albicans in combination with metagenomics and discovery metabolomics to identify changes in the community and metabolome during infection. To isolate the role of the microbiota in response to pathogens, we compared mice monocolonized with the pathogen, uninfected mice &quot;humanized&quot; with a synthetic human microbiome, or infected humanized mice. In Salmonella-infected mice, by 3 days into infection, microbiome community structure and function changed substantially, with a rise in Enterobacteriaceae strains and a reduction in biosynthetic gene cluster potential. In contrast, Candida-infected mice had few microbiome changes. The LC-MS metabolomic fingerprint of the cecum differed between mice monocolonized with either pathogen and humanized infected mice. Specifically, we identified an increase in glutathione disulfide, glutathione cysteine disulfide, inosine 5'-monophosphate, and hydroxybutyrylcarnitine in mice infected with Salmonella in contrast to uninfected mice and mice monocolonized with Salmonella These metabolites potentially play a role in pathogen-induced oxidative stress. These results provide insight into how the microbiota community members interact with each other and with pathogens on a metabolic level.IMPORTANCE The gut microbiota is increasingly recognized for playing a critical role in human health and disease, especially in conferring resistance to both virulent pathogens such as Salmonella, which infects 1.2 million people in the United States every year (E. Scallan, R. M. Hoekstra, F. J. Angulo, R. V. Tauxe, et al., Emerg Infect Dis 17:7-15, 2011, https://doi.org/10.3201/eid1701.P11101), and opportunistic pathogens like Candida, which causes an estimated 46,000 cases of invasive candidiasis each year in the United States (Centers for Disease Control and Prevention, Antibiotic Resistance Threats in the United States, 2013, 2013). Using a gnotobiotic mouse model, we investigate potential changes in gut microbial community structure and function during infection using metagenomics and metabolomics. We observe that changes in the community and in biosynthetic gene cluster potential occur within 3 days for the virulent Salmonella enterica serovar Typhimurium, but there are minimal changes with a poorly colonizing Candida albicans In addition, the metabolome shifts depending on infection status, including changes in glutathione metabolites in response to Salmonella infection, potentially in response to host oxidative stress.}, }
@article {pmid30400268, year = {2018}, author = {Ojo-Okunola, A and Nicol, M and du Toit, E}, title = {Human Breast Milk Bacteriome in Health and Disease.}, journal = {Nutrients}, volume = {10}, number = {11}, pages = {}, pmid = {30400268}, issn = {2072-6643}, support = {U01 AI110466/AI/NIAID NIH HHS/United States ; 1U01AI110466-01A1//H3Africa U01 AWARD FROM THE NATIONAL INSTITUTES OF HEALTH OF THE USA/ ; U54HG009824//NIH Office of the Director/ ; OPP1017641; OPP1017579//Bill and Melinda Gates Foundation/ ; U54 HG009824/HG/NHGRI NIH HHS/United States ; }, mesh = {Bacteria/isolation &amp; purification ; Feces/microbiology ; Female ; HIV Infections/microbiology/therapy ; Humans ; Infant ; Mastitis/microbiology/therapy ; *Microbiota ; Milk, Human/*microbiology ; Neoplasms/microbiology/therapy ; }, abstract = {It is well-known that, beyond nutritional components, human breast milk (HBM) contains a wide variety of non-nutritive bio-factors perfectly suited for the growing infant. In the pre-2000 era, HBM was considered sterile and devoid of micro-organisms. Though HBM was not included as part of the human microbiome project launched in 2007, great strides have been made in studying the bacterial diversity of HBM in both a healthy state and diseased state, and in understanding their role in infant health. HBM provides a vast array of beneficial micro-organisms that play a key role in colonizing the infant's mucosal system, including that of the gut. They also have a role in priming the infant's immune system and supporting its maturation. In this review, we provide an in-depth and updated insight into the immunomodulatory, metabolic, and anti-infective role of HBM bacteriome (bacterial community) and its effect on infant health. We also provide key information from the literature by exploring the possible origin of microbial communities in HBM, the bacterial diversity in this niche and the determinants influencing the HBM bacteriome. Lastly, we investigate the role of the HBM bacteriome in maternal infectious disease (human immunodeficiency virus (HIV) and mastitis)), and cancer. Key gaps in HBM bacterial research are also identified.}, }
@article {pmid30397357, year = {2018}, author = {Tirosh, O and Conlan, S and Deming, C and Lee-Lin, SQ and Huang, X and ,  and Su, HC and Freeman, AF and Segre, JA and Kong, HH}, title = {Expanded skin virome in DOCK8-deficient patients.}, journal = {Nature medicine}, volume = {24}, number = {12}, pages = {1815-1821}, pmid = {30397357}, issn = {1546-170X}, support = {Z01 HG000180-08//NULL/International ; ZIA AI001193-04//NULL/International ; ZIA BC010938-10//NULL/International ; }, mesh = {Adolescent ; Bacteriophages/genetics ; Child ; Female ; Genome, Viral/genetics ; Guanine Nucleotide Exchange Factors/deficiency/*genetics ; Healthy Volunteers ; Host Microbial Interactions/genetics/immunology ; Humans ; Immunity/genetics ; Immunologic Deficiency Syndromes/microbiology/pathology/*virology ; Lymphocytes/virology ; Male ; Metagenome/genetics/immunology ; Microbiota/genetics ; Papillomaviridae/isolation &amp; purification/pathogenicity ; Skin/microbiology/*virology ; Skin Diseases/genetics/microbiology/pathology/*virology ; }, abstract = {Human microbiome studies have revealed the intricate interplay of host immunity and bacterial communities to achieve homeostatic balance. Healthy skin microbial communities are dominated by bacteria with low viral representation1-3, mainly bacteriophage. Specific eukaryotic viruses have been implicated in both common and rare skin diseases, but cataloging skin viral communities has been limited. Alterations in host immunity provide an opportunity to expand our understanding of microbial-host interactions. Primary immunodeficient patients manifest with various viral, bacterial, fungal, and parasitic infections, including skin infections4. Dedicator of cytokinesis 8 (DOCK8) deficiency is a rare primary human immunodeficiency characterized by recurrent cutaneous and systemic infections, as well as atopy and cancer susceptibility5. DOCK8, encoding a guanine nucleotide exchange factor highly expressed in lymphocytes, regulates actin cytoskeleton, which is critical for migration through collagen-dense tissues such as skin6. Analyzing deep metagenomic sequencing data from DOCK8-deficient skin samples demonstrated a notable increase in eukaryotic viral representation and diversity compared with healthy volunteers. De novo assembly approaches identified hundreds of novel human papillomavirus genomes, illuminating microbial dark matter. Expansion of the skin virome in DOCK8-deficient patients underscores the importance of immune surveillance in controlling eukaryotic viral colonization and infection.}, }
@article {pmid30396009, year = {2019}, author = {Woerner, AE and Novroski, NMM and Wendt, FR and Ambers, A and Wiley, R and Schmedes, SE and Budowle, B}, title = {Forensic human identification with targeted microbiome markers using nearest neighbor classification.}, journal = {Forensic science international. Genetics}, volume = {38}, number = {}, pages = {130-139}, doi = {10.1016/j.fsigen.2018.10.003}, pmid = {30396009}, issn = {1878-0326}, mesh = {Biodiversity ; Forensic Genetics/methods ; High-Throughput Nucleotide Sequencing ; Humans ; *Microbiota ; Phylogeny ; Sequence Analysis, DNA ; Skin/*microbiology ; }, abstract = {From the perspective of forensics genetics, the human microbiome is a rich, relatively untapped resource for human identity testing. Since it varies within and among people, and perhaps temporally, the potential forensic applications of the use of the microbiome can exceed that of human identification. However, the same inherent variability in microbial distributions may pose a substantial barrier to forming predictions on an individual as the source of the microbial sample unless stable signatures of the microbiome are identified and targeted. One of the more commonly adopted strategies for microbial human identification relies on quantifying which taxa are present and their respective abundance levels. It remains an open question if such microbial signatures are more individualizing than estimates of the degree of genetic relatedness between microbial samples. This study attempts to address this question by contrasting two prediction strategies. The first approach uses phylogenetic distance to predict the host individual; thus it operates under the premise that microbes within individuals are more closely related than microbes between/among individuals. The second approach uses population genetic measures of diversity at clade-specific markers, serving as a fine-grained assessment of microbial composition and quantification. Both assessments were performed using targeted sequencing of 286 markers from 22 microbial taxa sampled in 51 individuals across three body sites measured in triplicate. Nearest neighbor and reverse nearest neighbor classifiers were constructed based on the pooled data and yielded 71% and 78% accuracy, respectively, when diversity was considered, and performed significantly worse when a phylogenetic distance was used (54% and 63% accuracy, respectively). However, empirical estimates of classification accuracy were 100% when conditioned on a maximum nearest neighbor distance when diversity was used, while identification based on a phylogenetic distance failed to reach saturation. These findings suggest that microbial strain composition is more individualizing than that of a phylogeny, perhaps indicating that microbial composition may be more individualizing than recent common ancestry. One inference that may be drawn from these findings is that host-environment interactions may maintain the targeted microbial profile and that this maintenance may not necessarily be repopulated by intra-individual microbial strains.}, }
@article {pmid30392721, year = {2018}, author = {Cogdill, AP and Gaudreau, PO and Arora, R and Gopalakrishnan, V and Wargo, JA}, title = {The Impact of Intratumoral and Gastrointestinal Microbiota on Systemic Cancer Therapy.}, journal = {Trends in immunology}, volume = {39}, number = {11}, pages = {900-920}, doi = {10.1016/j.it.2018.09.007}, pmid = {30392721}, issn = {1471-4981}, support = {R01 CA219896/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Gastrointestinal Tract/*immunology/microbiology ; Homeostasis ; Host-Pathogen Interactions ; Humans ; Immunity ; Immunotherapy/*methods ; Mice ; Microbiota/*physiology ; Neoplasms/microbiology/*therapy ; Tumor Microenvironment ; }, abstract = {The human microbiome is a complex aggregate of microorganisms, and their genomes exert a number of influences crucial to the metabolic, immunologic, hormonal, and homeostatic function of the host. Recent work, both in preclinical mouse models and human studies, has shed light on the impact of gut and tumor microbiota on responses to systemic anticancer therapeutics. In light of this, strategies to target the microbiome to improve therapeutic responses are underway, including efforts to target gut and intratumoral microbes. Here, we discuss mechanisms by which microbiota may impact systemic and antitumor immunity, in addition to outstanding questions in the field. A deeper understanding of these is critical as we devise putative strategies to target the microbiome.}, }
@article {pmid30390805, year = {2018}, author = {Wang, Q and Yang, F and Jia, H}, title = {Mining the Microbiome for Drug Targets.}, journal = {Methods in enzymology}, volume = {610}, number = {}, pages = {59-72}, doi = {10.1016/bs.mie.2018.09.014}, pmid = {30390805}, issn = {1557-7988}, mesh = {Drug Discovery/*methods ; Humans ; Metagenome/drug effects ; Metagenomics/*methods ; Microbiota/*drug effects ; Molecular Targeted Therapy/methods ; }, abstract = {The human microbiome is our &quot;other genome.&quot; Implicated in a growing list of complex diseases, for which genomic studies typically explain a portion of the disease susceptibility, the human gut microbiome has been at the spotlight for our understanding of human diseases. As the microbiome is intrinsically more variable than the human genome, it is important to take careful considerations at each step of a study. Here, we put forward our recommendations, which we envision would facilitate identification of true drug targets in the human microbiome in the colon as well as at other body sites.}, }
@article {pmid30390741, year = {2018}, author = {Wu, BG and Segal, LN}, title = {The Lung Microbiome and Its Role in Pneumonia.}, journal = {Clinics in chest medicine}, volume = {39}, number = {4}, pages = {677-689}, pmid = {30390741}, issn = {1557-8216}, support = {K23 AI102970/AI/NIAID NIH HHS/United States ; T32 CA193111/CA/NCI NIH HHS/United States ; UL1 TR001445/TR/NCATS NIH HHS/United States ; }, mesh = {Humans ; Inflammation/*complications/pathology ; Lung/*pathology ; Microbiota/*immunology ; Pneumonia/*microbiology ; }, abstract = {The use of next-generation sequencing and multiomic analysis reveals new insights on the identity of microbes in the lower airways blurring the lines between commensals and pathogens. Microbes are not found in isolation; rather they form complex metacommunities where microbe-host and microbe-microbe interactions play important roles on the host susceptibility to pathogens. In addition, the lower airway microbiota exert significant effects on host immune tone. Thus, this review highlights the roles that microbes in the respiratory tract play in the development of pneumonia.}, }
@article {pmid30389765, year = {2019}, author = {Junges, R and Sturød, K and Salvadori, G and Åmdal, HA and Chen, T and Petersen, FC}, title = {Characterization of a Signaling System in Streptococcus mitis That Mediates Interspecies Communication with Streptococcus pneumoniae.}, journal = {Applied and environmental microbiology}, volume = {85}, number = {2}, pages = {}, doi = {10.1128/AEM.02297-18}, pmid = {30389765}, issn = {1098-5336}, abstract = {Streptococcus mitis is found in the oral cavity and nasopharynx and forms a significant portion of the human microbiome. In this study, in silico analyses indicated the presence of an Rgg regulator and short hydrophobic peptide (Rgg/SHP) cell-to-cell communication system in S. mitis Although Rgg presented greater similarity to a repressor in Streptococcus pyogenes, autoinducing assays and genetic mutation analysis revealed that in S. mitis Rgg acts as an activator. Transcriptome analysis showed that in addition to shp, the system regulates two other downstream genes, comprising a segment of a putative lantibiotic gene cluster that is in a conjugative element locus in different members of the mitis group. Close comparison to a similar lantibiotic gene cluster in Streptococcus pneumoniae indicated that S. mitis lacked the full set of genes. Despite the potential of SHP to trigger a futile cycle of autoinduction, growth was not significantly affected for the rgg mutant under normal or antibiotic stress conditions. The S. mitis SHP was, however, fully functional in promoting cross-species communication and increasing S. pneumoniae surface polysaccharide production, which in this species is regulated by Rgg/SHP. The activity of SHPs produced by both species was detected in cocultures using a S. mitis reporter strain. In competitive assays, a slight advantage was observed for the rgg mutants. We conclude that the Rgg/SHP system in S. mitis regulates the expression of its own shp and activates an Rgg/SHP system in S. pneumoniae that regulates surface polysaccharide synthesis. Fundamentally, cross-communication of such systems may have a role during multispecies interactions.IMPORTANCE Bacteria secrete signal molecules into the environment which are sensed by other cells when the density reaches a certain threshold. In this study, we describe a communication system in Streptococcus mitis, a commensal species from the oral cavity, which we also found in several species and strains of streptococci from the mitis group. Further, we show that this system can promote cross-communication with S. pneumoniae, a closely related major human pathogen. Importantly, we show that this cross-communication can take place during coculture. While the genes regulated in S. mitis are likely part of a futile cycle of activation, the target genes in S. pneumoniae are potentially involved in virulence. The understanding of such complex communication networks can provide important insights into the dynamics of bacterial communities.}, }
@article {pmid30384329, year = {2018}, author = {Schooley, RT}, title = {The human microbiome: implications for health and disease, including HIV infection.}, journal = {Topics in antiviral medicine}, volume = {26}, number = {3}, pages = {75-78}, pmid = {30384329}, issn = {2161-5853}, mesh = {*Dysbiosis ; Female ; Gastrointestinal Microbiome ; HIV Infections/*complications ; Humans ; *Microbiota ; Vagina/microbiology ; Vaginosis, Bacterial ; }, abstract = {Our increased understanding of the human microbiome has brought insight into the role it plays in health and disease, including HIV infection. Studies have shown that the gut microbiome is less diverse in individuals with HIV infection than in noninfected control subjects. Efforts to modify the microbiome to bolster immune reconstitution in people with HIV infection have so far been unsuccessful. The vaginal microbiome affects risk of HIV acquisition, with Lactobacillus dominance being protective compared with vaginosis characterized by larger populations of Gardnerella. The vaginal microbiome might also affect efficacy of topical tenofovir disoproxil fumarate preexposure prophylaxis. This article summarizes a presentation by Robert T. Schooley, MD, at the IAS-USA continuing education program held in San Francisco in May 2018.}, }
@article {pmid30377376, year = {2018}, author = {Franzosa, EA and McIver, LJ and Rahnavard, G and Thompson, LR and Schirmer, M and Weingart, G and Lipson, KS and Knight, R and Caporaso, JG and Segata, N and Huttenhower, C}, title = {Species-level functional profiling of metagenomes and metatranscriptomes.}, journal = {Nature methods}, volume = {15}, number = {11}, pages = {962-968}, pmid = {30377376}, issn = {1548-7105}, support = {P30 DK043351/DK/NIDDK NIH HHS/United States ; U54 DE023798/DE/NIDCR NIH HHS/United States ; }, mesh = {Bacteria/*classification/*genetics/isolation &amp; purification ; Bacterial Proteins/*genetics/metabolism ; *Gene Expression Profiling ; High-Throughput Nucleotide Sequencing ; Humans ; *Metagenome ; Microbiota ; *Software ; Species Specificity ; *Transcriptome ; }, abstract = {Functional profiles of microbial communities are typically generated using comprehensive metagenomic or metatranscriptomic sequence read searches, which are time-consuming, prone to spurious mapping, and often limited to community-level quantification. We developed HUMAnN2, a tiered search strategy that enables fast, accurate, and species-resolved functional profiling of host-associated and environmental communities. HUMAnN2 identifies a community's known species, aligns reads to their pangenomes, performs translated search on unclassified reads, and finally quantifies gene families and pathways. Relative to pure translated search, HUMAnN2 is faster and produces more accurate gene family profiles. We applied HUMAnN2 to study clinal variation in marine metabolism, ecological contribution patterns among human microbiome pathways, variation in species' genomic versus transcriptional contributions, and strain profiling. Further, we introduce 'contributional diversity' to explain patterns of ecological assembly across different microbial community types.}, }
@article {pmid30374951, year = {2019}, author = {Vinberg, M and Ottesen, NM and Meluken, I and Sørensen, N and Pedersen, O and Kessing, LV and Miskowiak, KW}, title = {Remitted affective disorders and high familial risk of affective disorders associate with aberrant intestinal microbiota.}, journal = {Acta psychiatrica Scandinavica}, volume = {139}, number = {2}, pages = {174-184}, doi = {10.1111/acps.12976}, pmid = {30374951}, issn = {1600-0447}, support = {//Hørslev Foundation/ ; //The Research fund of the Capital Region of Denmark/ ; //Axel Thomsens Foundation/ ; //Novo Nordisk Foundation/ ; R108-A10015//Lundbeck Foundation/ ; //(Laegevidenskabens fremme) Foundation/ ; //Augustinus Foundation/ ; }, abstract = {OBJECTIVE: Affective disorders seem associated with aberrant intestinal microbiota but whether this pattern also occurs in individuals at increased heritable risk is unknown. We investigated associations between gut microbiota profiles and affective disorders by comparing monozygotic (MZ) twins concordant (affected twins with unipolar or bipolar disorder in remission) and discordant to affective disorders (high-risk) with MZ twins without affective disorders (low-risk).<br><br>METHODS: Stool samples were collected from 128 MZ twins and the microbiome was profiled using 16S rDNA sequencing of the V3-V4 region.<br><br>RESULTS: Affected twins had a lower diversity and an absence of a specific operational taxonomical unit (OTU) in comparison with low-risk twins. The high-risk twins exhibited the same pattern although the lower diversity was only at a trend level. The OTU belonged to the family Christensenellaceae. The findings were not explained by lifestyle factors (smoking, alcohol consumption, body mass index, or psychotropic medication).<br><br>CONCLUSION: Affected twins in remission and high-risk twins presented aberrant gut microbiota with depletion of a specific OTU. If replicated, this reduced relative sequence absence may together with the globally altered microbiota composition act as a vulnerability marker by accentuating the effect of gene-environment interactions in individuals genetically disposed for an affective disorder.}, }
@article {pmid30374830, year = {2019}, author = {Pretzl, B and Sälzer, S and Ehmke, B and Schlagenhauf, U and Dannewitz, B and Dommisch, H and Eickholz, P and Jockel-Schneider, Y}, title = {Administration of systemic antibiotics during non-surgical periodontal therapy-a consensus report.}, journal = {Clinical oral investigations}, volume = {23}, number = {7}, pages = {3073-3085}, doi = {10.1007/s00784-018-2727-0}, pmid = {30374830}, issn = {1436-3771}, support = {2.2-220.522-97/15_1//Commission for Young Scientists and Gender Equality, University of Wuerzburg/ ; 2.2-220.522-97/2015_1//IZKF/ ; }, abstract = {AIM: The aim of this meta-review was to evaluate whether there is a meaningful clinical benefit regarding the use of systemic adjunctive antibiotics in the treatment of patients with periodontitis. Additionally, a consensus regarding possible recommendations for future administration of antibiotics should be reached.<br><br>METHODS: A structured literature search was performed by two independent investigators focusing on systematic reviews (SR) covering adjunctive systemic antibiosis during non-surgical periodontal therapy. Additionally, recent randomized clinical trials (RCT, July 2015 to July 2017) were searched systematically to update the latest SR. Results were summarized and discussed in a plenary to reach a consensus.<br><br>RESULTS: Mostly, systematic reviews and RCTs showed a significant positive effect of adjunctive systematic antibiosis compared to controls. These positive effects gain clinical relevance in patients with severe periodontal disease aged 55 years and younger.<br><br>CONCLUSION: Systemic antibiotics as an adjunct to non-surgical periodontal therapy should be sensibly administered and restrictively used. Only certain groups of periodontitis patients show a significant and clinically relevant benefit after intake of systemic antibiosis during periodontal therapy.<br><br>CLINICAL RELEVANCE: Avoiding antibiotic resistance and possible side effects on the human microbiome should be a focus of dentists and physicians. Thus, a sensible administration of antibiotics is mandatory. This manuscript suggests guidelines for a reasonable use.}, }
@article {pmid30367598, year = {2018}, author = {Shi, JY and Huang, H and Zhang, YN and Cao, JB and Yiu, SM}, title = {BMCMDA: a novel model for predicting human microbe-disease associations via binary matrix completion.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 9}, pages = {281}, pmid = {30367598}, issn = {1471-2105}, mesh = {*Algorithms ; *Bacteria ; Bacterial Physiological Phenomena ; Computational Biology/*methods ; *Disease ; Host-Pathogen Interactions ; Humans ; *Microbiota ; *Models, Biological ; Risk Factors ; }, abstract = {BACKGROUND: Human Microbiome Project reveals the significant mutualistic influence between human body and microbes living in it. Such an influence lead to an interesting phenomenon that many noninfectious diseases are closely associated with diverse microbes. However, the identification of microbe-noninfectious disease associations (MDAs) is still a challenging task, because of both the high cost and the limitation of microbe cultivation. Thus, there is a need to develop fast approaches to screen potential MDAs. The growing number of validated MDAs enables us to meet the demand in a new insight. Computational approaches, especially machine learning, are promising to predict MDA candidates rapidly among a large number of microbe-disease pairs with the advantage of no limitation on microbe cultivation. Nevertheless, a few computational efforts at predicting MDAs are made so far.<br><br>RESULTS: In this paper, grouping a set of MDAs into a binary MDA matrix, we propose a novel predictive approach (BMCMDA) based on Binary Matrix Completion to predict potential MDAs. The proposed BMCMDA assumes that the incomplete observed MDA matrix is the summation of a latent parameterizing matrix and a noising matrix. It also assumes that the independently occurring subscripts of observed entries in the MDA matrix follows a binomial model. Adopting a standard mean-zero Gaussian distribution for the nosing matrix, we model the relationship between the parameterizing matrix and the MDA matrix under the observed microbe-disease pairs as a probit regression. With the recovered parameterizing matrix, BMCMDA deduces how likely a microbe would be associated with a particular disease. In the experiment under leave-one-out cross-validation, it exhibits the inspiring performance (AUC = 0.906, AUPR =0.526) and demonstrates its superiority by ~ 7% and ~ 5% improvements in terms of AUC and AUPR respectively in the comparison with the pioneering approach KATZHMDA.<br><br>CONCLUSIONS: Our BMCMDA provides an effective approach for predicting MDAs and can be also extended to other similar predicting tasks of binary relationship (e.g. protein-protein interaction, drug-target interaction).}, }
@article {pmid30356183, year = {2018}, author = {Vatanen, T and Franzosa, EA and Schwager, R and Tripathi, S and Arthur, TD and Vehik, K and Lernmark, Å and Hagopian, WA and Rewers, MJ and She, JX and Toppari, J and Ziegler, AG and Akolkar, B and Krischer, JP and Stewart, CJ and Ajami, NJ and Petrosino, JF and Gevers, D and Lähdesmäki, H and Vlamakis, H and Huttenhower, C and Xavier, RJ}, title = {The human gut microbiome in early-onset type 1 diabetes from the TEDDY study.}, journal = {Nature}, volume = {562}, number = {7728}, pages = {589-594}, doi = {10.1038/s41586-018-0620-2}, pmid = {30356183}, issn = {1476-4687}, support = {UC4 DK063861/DK/NIDDK NIH HHS/United States ; UC4 DK095300/DK/NIDDK NIH HHS/United States ; UC4 DK063836/DK/NIDDK NIH HHS/United States ; UL1 TR000064/TR/NCATS NIH HHS/United States ; UC4 DK063821/DK/NIDDK NIH HHS/United States ; UC4 DK063865/DK/NIDDK NIH HHS/United States ; U01 DK063821/DK/NIDDK NIH HHS/United States ; U54 DE023798/DE/NIDCR NIH HHS/United States ; HHSN267200700014C/DK/NIDDK NIH HHS/United States ; U01 DK063836/DK/NIDDK NIH HHS/United States ; UC4 DK100238/DK/NIDDK NIH HHS/United States ; UC4 DK063863/DK/NIDDK NIH HHS/United States ; UC4 DK106955/DK/NIDDK NIH HHS/United States ; UL1 TR001082/TR/NCATS NIH HHS/United States ; UC4 DK063829/DK/NIDDK NIH HHS/United States ; U01 DK063865/DK/NIDDK NIH HHS/United States ; UL1 TR001427/TR/NCATS NIH HHS/United States ; U01 DK063829/DK/NIDDK NIH HHS/United States ; R24 DK110499/DK/NIDDK NIH HHS/United States ; UC4 DK112243/DK/NIDDK NIH HHS/United States ; U01 DK063790/DK/NIDDK NIH HHS/United States ; P30 DK048520/DK/NIDDK NIH HHS/United States ; UC4 DK117483/DK/NIDDK NIH HHS/United States ; U01 DK063861/DK/NIDDK NIH HHS/United States ; U01 DK063863/DK/NIDDK NIH HHS/United States ; }, mesh = {Age of Onset ; Animals ; Bifidobacterium/enzymology/genetics/isolation &amp; purification ; Breast Feeding ; Child, Preschool ; Diabetes Mellitus, Type 1/*epidemiology/genetics/*microbiology/prevention &amp; control ; Disease Models, Animal ; European Continental Ancestry Group ; Fatty Acids, Volatile/pharmacology ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/genetics/immunology/*physiology ; *Health Surveys ; Humans ; Infant ; Islets of Langerhans/immunology ; Longitudinal Studies ; Male ; Mice ; Milk, Human/immunology/microbiology ; Proteobacteria/enzymology/genetics/isolation &amp; purification ; }, abstract = {Type 1 diabetes (T1D) is an autoimmune disease that targets pancreatic islet beta cells and incorporates genetic and environmental factors1, including complex genetic elements2, patient exposures3 and the gut microbiome4. Viral infections5 and broader gut dysbioses6 have been identified as potential causes or contributing factors; however, human studies have not yet identified microbial compositional or functional triggers that are predictive of islet autoimmunity or T1D. Here we analyse 10,913 metagenomes in stool samples from 783 mostly white, non-Hispanic children. The samples were collected monthly from three months of age until the clinical end point (islet autoimmunity or T1D) in the The Environmental Determinants of Diabetes in the Young (TEDDY) study, to characterize the natural history of the early gut microbiome in connection to islet autoimmunity, T1D diagnosis, and other common early life events such as antibiotic treatments and probiotics. The microbiomes of control children contained more genes that were related to fermentation and the biosynthesis of short-chain fatty acids, but these were not consistently associated with particular taxa across geographically diverse clinical centres, suggesting that microbial factors associated with T1D are taxonomically diffuse but functionally more coherent. When we investigated the broader establishment and development of the infant microbiome, both taxonomic and functional profiles were dynamic and highly individualized, and dominated in the first year of life by one of three largely exclusive Bifidobacterium species (B. bifidum, B. breve or B. longum) or by the phylum Proteobacteria. In particular, the strain-specific carriage of genes for the utilization of human milk oligosaccharide within a subset of B. longum was present specifically in breast-fed infants. These analyses of TEDDY gut metagenomes provide, to our knowledge, the largest and most detailed longitudinal functional profile of the developing gut microbiome in relation to islet autoimmunity, T1D and other early childhood events. Together with existing evidence from human cohorts7,8 and a T1D mouse model9, these data support the protective effects of short-chain fatty acids in early-onset human T1D.}, }
@article {pmid30355348, year = {2018}, author = {Tackmann, J and Arora, N and Schmidt, TSB and Rodrigues, JFM and von Mering, C}, title = {Ecologically informed microbial biomarkers and accurate classification of mixed and unmixed samples in an extensive cross-study of human body sites.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {192}, pmid = {30355348}, issn = {2049-2618}, mesh = {Bacteria/*classification/*genetics ; Biomarkers/analysis ; DNA, Bacterial/*genetics ; Genome, Bacterial/*genetics ; Human Body ; Humans ; Machine Learning ; Microbiota/*genetics ; }, abstract = {BACKGROUND: The identification of body site-specific microbial biomarkers and their use for classification tasks have promising applications in medicine, microbial ecology, and forensics. Previous studies have characterized site-specific microbiota and shown that sample origin can be accurately predicted by microbial content. However, these studies were usually restricted to single datasets with consistent experimental methods and conditions, as well as comparatively small sample numbers. The effects of study-specific biases and statistical power on classification performance and biomarker identification thus remain poorly understood. Furthermore, reliable detection in mixtures of different body sites or with noise from environmental contamination has rarely been investigated thus far. Finally, the impact of ecological associations between microbes on biomarker discovery was usually not considered in previous work.<br><br>RESULTS: Here we present the analysis of one of the largest cross-study sequencing datasets of microbial communities from human body sites (15,082 samples from 57 publicly available studies). We show that training a Random Forest Classifier on this aggregated dataset increases prediction performance for body sites by 35% compared to a single-study classifier. Using simulated datasets, we further demonstrate that the source of different microbial contributions in mixtures of different body sites or with soil can be detected starting at 1% of the total microbial community. We apply a biomarker selection method that excludes indirect environmental associations driven by microbe-microbe associations, yielding a parsimonious set of highly predictive taxa including novel biomarkers and excluding many previously reported taxa. We find a considerable fraction of unclassified biomarkers (&quot;microbial dark matter&quot;) and observe that negatively associated taxa have a surprisingly high impact on classification performance. We further detect a significant enrichment of rod-shaped, motile, and sporulating taxa for feces biomarkers, consistent with a highly competitive environment.<br><br>CONCLUSIONS: Our machine learning model shows strong body site classification performance, both in single-source samples and mixtures, making it promising for tasks requiring high accuracy, such as forensic applications. We report a core set of ecologically informed biomarkers, inferred across a wide range of experimental protocols and conditions, providing the most concise, general, and least biased overview of body site-associated microbes to date.}, }
@article {pmid30352623, year = {2018}, author = {Benler, S and Cobián-Güemes, AG and McNair, K and Hung, SH and Levi, K and Edwards, R and Rohwer, F}, title = {A diversity-generating retroelement encoded by a globally ubiquitous Bacteroides phage.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {191}, pmid = {30352623}, issn = {2049-2618}, mesh = {Bacteroides/genetics/*virology ; Genome, Viral/*genetics ; Humans ; Metagenome/genetics ; Prophages/*genetics ; Retroelements/*genetics ; Viral Tail Proteins/*genetics ; }, abstract = {BACKGROUND: Diversity-generating retroelements (DGRs) are genetic cassettes that selectively mutate target genes to produce hypervariable proteins. First characterized in Bordetella bacteriophage BPP-1, the DGR creates a hypervariable phage tail fiber that enables host tropism switching. Subsequent surveys for DGRs conclude that the majority identified to date are bacterial or archaeal in origin. This work examines bacteriophage and bacterial genomes for novel phage-encoded DGRs.<br><br>RESULTS: This survey discovered 92 DGRs that were only found in phages exhibiting a temperate lifestyle. The majority of phage-encoded DGRs were identified as prophages in bacterial hosts from the phyla Bacteroidetes, Proteobacteria, and Firmicutes. Sequence reads from these previously unidentified prophages were present in viral metagenomes (viromes), indicating these prophages can produce functional viruses. Five phages possessed hypervariable proteins with structural similarity to the tail fiber of BPP-1, whereas the functions of the remaining DGR target proteins were unknown. A novel temperate phage that harbors a DGR cassette targeting a protein of unknown function was induced from Bacteroides dorei. This phage, here named Bacteroides dorei Hankyphage, lysogenizes 13 different Bacteroides species and was present in 34% and 21% of whole-community metagenomes and human-associated viromes, respectively.<br><br>CONCLUSIONS: Here, the number of known DGR-containing phages is increased from four to 92. All of these phages exhibit a temperate lifestyle, including a cosmopolitan human-associated phage. Targeted hypervariation by temperate phages may be a ubiquitous mechanism underlying phage-bacteria interaction in the human microbiome.}, }
@article {pmid30349509, year = {2018}, author = {Chaudhari, NM and Gautam, A and Gupta, VK and Kaur, G and Dutta, C and Paul, S}, title = {PanGFR-HM: A Dynamic Web Resource for Pan-Genomic and Functional Profiling of Human Microbiome With Comparative Features.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {2322}, pmid = {30349509}, issn = {1664-302X}, abstract = {The conglomerate of microorganisms inhabiting various body-sites of human, known as the human microbiome, is one of the key determinants of human health and disease. Comprehensive pan-genomic and functional analysis approach for human microbiome components can enrich our understanding about impact of microbiome on human health. By utilizing this approach we developed PanGFR-HM (http://www.bioinfo.iicb.res.in/pangfr-hm/) - a novel dynamic web-resource that integrates genomic and functional characteristics of 1293 complete microbial genomes available from Human Microbiome Project. The resource allows users to explore genomic/functional diversity and genome-based phylogenetic relationships between human associated microbial genomes, not provided by any other resource. The key features implemented here include pan-genome and functional analysis of organisms based on taxonomy or body-site, and comparative analysis between groups of organisms. The first feature can also identify probable gene-loss events and significantly over/under represented KEGG/COG categories within pan-genome. The unique second feature can perform comparative genomic, functional and pathways analysis between 4 groups of microbes. The dynamic nature of this resource enables users to define parameters for orthologous clustering and to select any set of organisms for analysis. As an application for comparative feature of PanGFR-HM, we performed a comparative analysis with 67 Lactobacillus genomes isolated from human gut, oral cavity and urogenital tract, and therefore characterized the body-site specific genes, enzymes and pathways. Altogether, PanGFR-HM, being unique in its content and functionality, is expected to provide a platform for microbiome-based comparative functional and evolutionary genomics.}, }
@article {pmid30349024, year = {2018}, author = {Chen, Z and Yeoh, YK and Hui, M and Wong, PY and Chan, MCW and Ip, M and Yu, J and Burk, RD and Chan, FKL and Chan, PKS}, title = {Diversity of macaque microbiota compared to the human counterparts.}, journal = {Scientific reports}, volume = {8}, number = {1}, pages = {15573}, pmid = {30349024}, issn = {2045-2322}, abstract = {Studies on the microbial communities in non-human primate hosts provide unique insights in both evolution and function of microbes related to human health and diseases. Using 16S rRNA gene amplicon profiling, we examined the oral, anal and vaginal microbiota in a group of non-captive rhesus macaques (N = 116) and compared the compositions with the healthy communities from Human Microbiome Project. The macaque microbiota was dominated by Bacteroidetes, Firmicutes and Proteobacteria; however, there were marked differences in phylotypes enriched across body sites indicative of strong niche specialization. Compared to human gut microbiota where Bacteroides predominately enriched, the surveyed macaque anal community exhibited increased abundance of Prevotella. In contrast to the conserved human vaginal microbiota extremely dominated by Lactobacillus, the macaque vaginal microbial composition was highly diverse while lactobacilli were rare. A constant decrease of the vaginal microbiota diversity was observed among macaque samples from juvenile, adult without tubectomy, and adult with tubectomy, with the most notable distinction being the enrichment of Halomonas in juvenile and Saccharofermentans in contracepted adults. Both macaque and human oral microbiota were colonized with three most common oral bacterial genera: Streptococcus, Haemophilus and Veillonella, and shared relatively conserved communities to each other. A number of bacteria related to human pathogens were consistently detected in macaques. The findings delineate the range of structure and diversity of microbial communities in a wild macaque population, and enable the application of macaque as an animal model for future characterization of microbes in transmission, genomics and function.}, }
@article {pmid30345704, year = {2018}, author = {Ponziani, FR and Putignani, L and Paroni Sterbini, F and Petito, V and Picca, A and Del Chierico, F and Reddel, S and Calvani, R and Marzetti, E and Sanguinetti, M and Gasbarrini, A and Pompili, M}, title = {Influence of hepatitis C virus eradication with direct-acting antivirals on the gut microbiota in patients with cirrhosis.}, journal = {Alimentary pharmacology &amp; therapeutics}, volume = {48}, number = {11-12}, pages = {1301-1311}, doi = {10.1111/apt.15004}, pmid = {30345704}, issn = {1365-2036}, abstract = {BACKGROUND: The cure of hepatitis C virus (HCV) infection may contribute to the reduction of liver fibrosis progression and potentially influence the gut-liver axis.<br><br>AIM: To investigate the influence of HCV infection eradication with direct-acting antivirals (DAAs) on the gut microbiota composition as well as on intestinal and systemic inflammatory parameters in patients with cirrhosis.<br><br>METHODS: Consecutive patients with HCV-related cirrhosis receiving DAA treatment were included. The gut microbiota composition, intestinal permeability, and inflammation were assessed before treatment and after 1 year. Clinical outcomes such as episodes of decompensation and markers of liver fibrosis were evaluated over a 2-year follow-up period.<br><br>RESULTS: The gut microbiota alpha diversity in cirrhotic patients, which was lower than that in healthy subjects, was significantly improved by the cure of HCV infection and a shift in the overall gut microbiota composition was observed compared to baseline. The abundance of potentially pathogenic bacteria (Enterobacteriaceae, Enterococcus, and Staphylococcus) was decreased after treatment. The gut microbiota composition was associated with the inflammatory profile and markers of liver fibrosis. Although a significant reduction in the serum levels of cytokines and chemokines was observed post-DAA treatment, measures of intestinal permeability and inflammation remained unchanged.<br><br>CONCLUSIONS: Cure of HCV infection with DAAs in patients with cirrhosis is associated with a modification of the gut microbiota, which correlates with fibrosis and inflammation but does not improve intestinal barrier function.}, }
@article {pmid30345066, year = {2018}, author = {Duran-Pinedo, AE and Solbiati, J and Frias-Lopez, J}, title = {The effect of the stress hormone cortisol on the metatranscriptome of the oral microbiome.}, journal = {NPJ biofilms and microbiomes}, volume = {4}, number = {}, pages = {25}, pmid = {30345066}, issn = {2055-5008}, support = {R01 DE021553/DE/NIDCR NIH HHS/United States ; }, abstract = {Imbalances of the microbiome, also referred to as microbial dysbiosis, could lead to a series of different diseases. One factor that has been shown to lead to dysbiosis of the microbiome is exposure to psychological stressors. Throughout evolution microorganisms of the human microbiome have developed systems for sensing host-associated signals such as hormones associated with those stressors, enabling them to recognize essential changes in their environment, thus changing their expression gene profile to fit the needs of the new environment. The most widely accepted theory explaining the ability of hormones to affect the outcome of an infection involves the suppression of the immune system. Commensal microbiota is involved in stressor-induced immunomodulation, but other biological effects are not yet known. Here we present the impact that cortisol had on the community-wide transcriptome of the oral community. We used a metatranscriptomic approach to obtain first insights into the metabolic changes induced by this stress hormone as well as which members of the oral microbiome respond to the presence of cortisol in the environment. Our findings show that the stress hormone cortisol directly induces shifts in the gene expression profiles of the oral microbiome that reproduce results found in the profiles of expression of periodontal disease and its progression.}, }
@article {pmid30342346, year = {2018}, author = {Chen, B and Wang, J and Wang, Y and Zhang, J and Zhao, C and Shen, N and Yang, J and Gai, Z and Zhang, L}, title = {Oral microbiota dysbiosis and its association with Henoch-Schönlein Purpura in children.}, journal = {International immunopharmacology}, volume = {65}, number = {}, pages = {295-302}, doi = {10.1016/j.intimp.2018.10.017}, pmid = {30342346}, issn = {1878-1705}, mesh = {Adolescent ; Bacteroidetes/*physiology ; Child ; Child, Preschool ; Dysbiosis/immunology/*microbiology ; Female ; Firmicutes/*physiology ; Humans ; Male ; Microbiota/*immunology ; Mouth/*microbiology ; Proteobacteria/*physiology ; Purpura, Schoenlein-Henoch/immunology/*microbiology ; RNA, Ribosomal, 16S/genetics ; }, abstract = {BACKGROUND: The pathogenesis of microbes in allergic diseases has been demonstrated and our previous research indicates that microbiota causing gut disorders in children is associated with Henoch-Schönlein Purpura. However, the role of oral microbiota in Henoch-Schönlein Purpura remains unknown.<br><br>METHOD: A total of 164 children were enrolled, of which 98 were patients with HSP and 66 were healthy children. Oral swab samples were collected for DNA extraction and 16S rRNA gene sequencing, then analyzed for oral microbiota composition.<br><br>RESULTS: Oral microbiota differed between healthy children and those with HSP. Children with HSP exhibited higher oral microbial diversity and richness than the controls. Firmicutes, Proteobacteria, and Bacteroidetes are the dominant phyla in children with HSP. We used linear discriminant analysis (LDA) effect size (LEfSe) algorithm and detected 21 bacterial taxonomic clades showing statistical differences (12 increased and 9 decreased) in children with HSP. The correlation analyses between clinical data and abundance in microbial community indicated that an abundance of Butyrivibrio sp. negatively correlated with the length of hospital stay (LOS). Haemophilus sp. negatively correlated to IgE and IgM but positively correlated to LOS, with decreasing significantly in patients with HSP. Prevotella positively correlated with IgM. Prevotella nanceiensis positively correlated with IgA, and were abundant in children with HSP.<br><br>CONCLUSIONS: These results indicate that children with HSP have significantly different oral microbiota compared to healthy children. Although this study does not imply causality, it is helpful to identify the types and pathways of bacteria that can be used to prevent or treat HSP.}, }
@article {pmid30332487, year = {2018}, author = {Wyman, SK and Avila-Herrera, A and Nayfach, S and Pollard, KS}, title = {A most wanted list of conserved microbial protein families with no known domains.}, journal = {PloS one}, volume = {13}, number = {10}, pages = {e0205749}, pmid = {30332487}, issn = {1932-6203}, mesh = {Bacterial Proteins/*chemistry/genetics ; Computational Biology ; *Databases, Nucleic Acid ; Humans ; Metagenome/*genetics ; Metagenomics ; Microbiota/*genetics ; Phylogeny ; Protein Domains/*genetics ; Sequence Homology, Nucleic Acid ; }, abstract = {The number and proportion of genes with no known function are growing rapidly. To quantify this phenomenon and provide criteria for prioritizing genes for functional characterization, we developed a bioinformatics pipeline that identifies robustly defined protein families with no annotated domains, ranks these with respect to phylogenetic breadth, and identifies them in metagenomics data. We applied this approach to 271 965 protein families from the SFams database and discovered many with no functional annotation, including >118 000 families lacking any known protein domain. From these, we prioritized 6 668 conserved protein families with at least three sequences from organisms in at least two distinct classes. These Function Unknown Families (FUnkFams) are present in Tara Oceans Expedition and Human Microbiome Project metagenomes, with distributions associated with sampling environment. Our findings highlight the extent of functional novelty in sequence databases and establish an approach for creating a &quot;most wanted&quot; list of genes to prioritize for further characterization.}, }
@article {pmid30324342, year = {2018}, author = {Waterhouse, M and Hope, B and Krause, L and Morrison, M and Protani, MM and Zakrzewski, M and Neale, RE}, title = {Vitamin D and the gut microbiome: a systematic review of in vivo studies.}, journal = {European journal of nutrition}, volume = {}, number = {}, pages = {}, doi = {10.1007/s00394-018-1842-7}, pmid = {30324342}, issn = {1436-6215}, abstract = {PURPOSE: Variation in the human microbiome has been linked with a variety of physiological functions, including immune regulation and metabolism and biosynthesis of vitamins, hormones, and neurotransmitters. Evidence for extraskeletal effects of vitamin D has been accruing and it has been suggested that the effect of vitamin D on health is partially mediated through the microbiome. We aimed to critically evaluate the evidence linking vitamin D and the gastrointestinal microbiome.<br><br>METHODS: We systematically searched the Embase, Web of Science, PubMed and CINAHL databases, including peer-reviewed publications that reported an association between a measure of vitamin D and the gastrointestinal microbiome in humans or experimental animals.<br><br>RESULTS: We included 10 mouse and 14 human studies. Mouse studies compared mice fed diets containing different levels of vitamin D (usually high versus low), or vitamin D receptor knockout or Cyp27B1 knockout with wild-type mice. Five mouse studies reported an increase in Bacteroidetes (or taxa within that phylum) in the low vitamin D diet or gene knockout group. Human studies were predominantly observational; all but two of the included studies found some association between vitamin D and the gut microbiome, but the nature of differences observed varied across studies.<br><br>CONCLUSIONS: Despite substantial heterogeneity, we found evidence to support the hypothesis that vitamin D influences the composition of the gastrointestinal microbiome. However, the research is limited, having been conducted either in mice or in mostly small, selected human populations. Future research in larger population-based studies is needed to fully understand the extent to which vitamin D modulates the microbiome.}, }
@article {pmid30311407, year = {2019}, author = {Bilen, M and Mbogning Fonkou, MD and Khelaifia, S and Tomei, E and Cadoret, F and Daoud, Z and Armstrong, N and Bittar, F and Fournier, PE and Raoult, D and Dubourg, G}, title = {Taxonogenomics description of Parabacteroides timonensis sp. nov. isolated from a human stool sample.}, journal = {MicrobiologyOpen}, volume = {8}, number = {4}, pages = {e00702}, doi = {10.1002/mbo3.702}, pmid = {30311407}, issn = {2045-8827}, mesh = {Adult ; Bacterial Typing Techniques ; Bacteroidetes/classification/genetics/*isolation &amp; purification ; Base Composition ; DNA, Bacterial/genetics ; Feces/*microbiology ; Gastrointestinal Microbiome ; Genome, Bacterial ; Genomics ; Humans ; Male ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; }, abstract = {Intensive efforts have been made to describe the human microbiome and its involvement in health and disease. Culturomics has been recently adapted to target formerly uncultured bacteria and other unclassified bacterial species. This approach enabled us to isolate in the current study a new bacterial species, Parabacteroides timonensis strain Marseille-P3236T , from a stool sample of a healthy 39-year-old pygmy male. This strain, is an anaerobic, gram-negative, nonspore-forming motile rod. Its genome is made up of 6,483,434 bp with 43.41% G+C content, 5046 protein-encoding genes, and 84 RNA genes. We herein provide the full description of Parabacteroides timonensis strain Marseille-P3236T through the taxonogenomic approach.}, }
@article {pmid30302512, year = {2019}, author = {Balato, A and Cacciapuoti, S and Di Caprio, R and Marasca, C and Masarà, A and Raimondo, A and Fabbrocini, G}, title = {Human Microbiome: Composition and Role in Inflammatory Skin Diseases.}, journal = {Archivum immunologiae et therapiae experimentalis}, volume = {67}, number = {1}, pages = {1-18}, doi = {10.1007/s00005-018-0528-4}, pmid = {30302512}, issn = {1661-4917}, mesh = {Acne Vulgaris/drug therapy/immunology/*microbiology ; Adolescent ; Adult ; Age Factors ; Aged ; Aged, 80 and over ; Anti-Bacterial Agents/therapeutic use ; Anti-Inflammatory Agents/therapeutic use ; *Bacteria/classification/drug effects/immunology/pathogenicity ; Child ; Child, Preschool ; Dermatitis, Atopic/drug therapy/immunology/*microbiology ; Dermatologic Agents/therapeutic use ; Dysbiosis ; *Gastrointestinal Microbiome/drug effects ; Hidradenitis Suppurativa/drug therapy/immunology/*microbiology ; Host-Pathogen Interactions ; Humans ; Infant ; Infant, Newborn ; Middle Aged ; Psoriasis/drug therapy/immunology/*microbiology ; Skin/drug effects/immunology/*microbiology ; Young Adult ; }, abstract = {This review focuses on recent evidences about human microbiome composition and functions, exploring the potential implication of its impairment in some diffuse and invalidating inflammatory skin diseases, such as atopic dermatitis, psoriasis, hidradenitis suppurativa and acne. We analysed current scientific literature, focusing on the current evidences about gut and skin microbiome composition and the complex dialogue between microbes and the host. Finally, we examined the consequences of this dialogue for health and skin diseases. This review highlights how human microbes interact with different anatomic niches modifying the state of immune activation, skin barrier status, microbe-host and microbe-microbe interactions. It also shows as most of the factors affecting gut and skin microorganisms' activity have demonstrated to be effective also in modulating chronic inflammatory skin diseases. More and more evidences demonstrate that human microbiome plays a key role in human health and diseases. It is to be expected that these new insights will translate into diagnostic, therapeutic and preventive measures in the context of personalized/precision medicine.}, }
@article {pmid30298527, year = {2019}, author = {Bell, JS and Spencer, JI and Yates, RL and Yee, SA and Jacobs, BM and DeLuca, GC}, title = {Invited Review: From nose to gut - the role of the microbiome in neurological disease.}, journal = {Neuropathology and applied neurobiology}, volume = {45}, number = {3}, pages = {195-215}, doi = {10.1111/nan.12520}, pmid = {30298527}, issn = {1365-2990}, abstract = {Inflammation and neurodegeneration are key features of many chronic neurological diseases, yet the causative mechanisms underlying these processes are poorly understood. There has been mounting interest in the role of the human microbiome in modulating the inflammatory milieu of the central nervous system (CNS) in health and disease. To date, most research has focussed on a gut-brain axis, with other mucosal surfaces being relatively neglected. We herein take the novel approach of comprehensively reviewing the roles of the microbiome across several key mucosal interfaces - the nose, mouth, lung and gut - in health and in Parkinson's disease (PD), Alzheimer's disease (AD) and multiple sclerosis (MS). This review systematically appraises the anatomical and microbiological landscape of each mucosal surface in health and disease before considering relevant mechanisms that may influence the initiation and progression of PD, AD and MS. The cumulative effects of dysbiosis from the nose to the gut may contribute significantly to neurological disease through a wide variety of mechanisms, including direct translocation of bacteria and their products, and modulation of systemic or CNS-specific immunity. This remains an understudied and exciting area for future research and may lead to the development of therapeutic targets for chronic neurological disease.}, }
@article {pmid30298256, year = {2018}, author = {Macklaim, JM and Gloor, GB}, title = {From RNA-seq to Biological Inference: Using Compositional Data Analysis in Meta-Transcriptomics.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {1849}, number = {}, pages = {193-213}, doi = {10.1007/978-1-4939-8728-3_13}, pmid = {30298256}, issn = {1940-6029}, mesh = {Bacteria/classification/*genetics/isolation &amp; purification ; Computational Biology/*methods ; Gene Expression Profiling/*methods ; High-Throughput Nucleotide Sequencing/*methods ; Humans ; *Metagenome ; *Microbiota ; *Transcriptome ; }, abstract = {The proper analysis of high-throughput sequencing datasets of mixed microbial communities (meta-transcriptomics) is substantially more complex than for datasets composed of single organisms. Adapting commonly used RNA-seq methods to the analysis of meta-transcriptome datasets can be misleading and not use all the available information in a consistent manner. However, meta-transcriptomic experiments can be investigated in a principled manner using Bayesian probabilistic modeling of the data at a functional level coupled with analysis under a compositional data analysis paradigm. We present a worked example for the differential functional evaluation of mixed-species microbial communities obtained from human clinical samples that were sequenced on an Illumina platform. We demonstrate methods to functionally map reads directly, conduct a compositionally appropriate exploratory data analysis, evaluate differential relative abundance, and finally identify compositionally associated (constant ratio) functions. Using these approaches we have found that meta-transcriptomic functional analyses are highly reproducible and convey significant information regarding the ecosystem.}, }
@article {pmid30283425, year = {2018}, author = {Hoggard, M and Vesty, A and Wong, G and Montgomery, JM and Fourie, C and Douglas, RG and Biswas, K and Taylor, MW}, title = {Characterizing the Human Mycobiota: A Comparison of Small Subunit rRNA, ITS1, ITS2, and Large Subunit rRNA Genomic Targets.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {2208}, pmid = {30283425}, issn = {1664-302X}, abstract = {Interest in the human microbiome has increased dramatically in the last decade. However, much of this research has focused on bacteria, while the composition and roles of their fungal counterparts remain less understood. Furthermore, a variety of methodological approaches have been applied, and the comparability between studies is unclear. This study compared four primer pairs targeting the small subunit (SSU) rRNA (18S), ITS1, ITS2, and large subunit (LSU) rRNA (26S) genomic regions for their ability to accurately characterize fungal communities typical of the human mycobiota. All four target regions of 21 individual fungal mock community taxa were capable of being amplified adequately and sequenced. Mixed mock community analyses revealed marked variability in the ability of each primer pair to accurately characterize a complex community. ITS target regions outperformed LSU and SSU. Of the ITS regions, ITS1 failed to generate sequences for Yarrowia lipolytica and all three Malassezia species when in a mixed community. These findings were further supported in studies of human sinonasal and mouse fecal samples. Based on these analyses, previous studies using ITS1, SSU, or LSU markers may omit key taxa that are identified by the ITS2 marker. Of methods commonly used in human mycobiota studies to date, we recommend selection of the ITS2 marker. Further investigation of more recently developed fungal primer options will be essential to ultimately determine the optimal methodological approach by which future human mycobiota studies ought to be standardized.}, }
@article {pmid30280754, year = {2018}, author = {Romano, L and Gualtieri, P and Nicoletti, F and Merra, G}, title = {Neurodegenerative disorders, gut human microbiome and diet: future research for prevention and supportive therapies.}, journal = {European review for medical and pharmacological sciences}, volume = {22}, number = {18}, pages = {5771-5772}, doi = {10.26355/eurrev_201809_15901}, pmid = {30280754}, issn = {2284-0729}, }
@article {pmid30277147, year = {2018}, author = {Vamanu, E}, title = {Complementary Functional Strategy for Modulation of Human Gut Microbiota.}, journal = {Current pharmaceutical design}, volume = {24}, number = {35}, pages = {4144-4149}, doi = {10.2174/1381612824666181001154242}, pmid = {30277147}, issn = {1873-4286}, abstract = {Two pathologies commonly associated with gut microbiota dysbiosis are type 2 diabetes and cardiovascular diseases. Since diet and medication are two important causes of microbiome fingerprint modifications, new complementary and alternative methods can include wild edible mushrooms, which serve as functional products, given their properties in modulating the microbial pattern at the colon level. A disturbance in microbial balance translates into the occurrence of degenerative dysfunctions that are also associated with other pathologies, such as obesity, colon cancer. The metagenomic study has enabled the identification of some competitive microbiological and biochemical biomarkers which allow the development of innovative strategies in controling microbial disbalance from human gut. Thus, the aim of this review was to present the significant findings related to human microbiome modulation via the prebiotic effects of wild edible mushrooms as a complementary strategy to modern treatment. Certain mushroom species have been approached and their effects on the microbiota fingerprint of two major target groups are highlighted.}, }
@article {pmid30276729, year = {2019}, author = {Perkins, RC}, title = {Making the Case for Functional Proteomics.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {1871}, number = {}, pages = {1-40}, doi = {10.1007/978-1-4939-8814-3_1}, pmid = {30276729}, issn = {1940-6029}, mesh = {Animals ; Biomarkers ; Drug Discovery/methods ; Genome ; Genomics/methods ; Humans ; Molecular Diagnostic Techniques ; Precision Medicine/methods ; *Proteome ; *Proteomics/methods ; Systems Biology/methods ; }, abstract = {&quot;Making the Case for Functional Proteomics&quot; first differentiates the Functional Proteome from the products of genetic protein expression. Qualitatively, the prevalence of posttranslational modifications (PTMs) virtually insures that individual, functional proteins do not equate to their genetic expression counterparts. Quantitatively, considering the frequency of PTMs and a conservative estimate of the number of functional entities arising from protein interactions, the size of the Functional Proteome exceeds that of the human genome by at least two orders of magnitude. The human genome does not, cannot, map the Functional Proteome. Further, the collective genome of the human microbiome dwarfs the human genome. With these facts established, &quot;Making the Case…&quot; proceeds to examine Functional Proteomics (of which both &quot;gene expression&quot; and &quot;epigenetics&quot; are but parts of a larger whole) within the context of Systems Biology, concluding that functionally related networks comprise the dominant motif for biological activity. Creating just such a network focus is essential in not only expanding basic knowledge but also in applying that knowledge in the pragmatic efforts of drug and biomarker development. Outlines for development of drugs and biomarkers, as well as the realization of precision medicine, within a functional proteomics-based, network motif are provided. The chapter proceeds to asses both the knowledge base and the tools to fully embrace Functional Proteomics. Given the decades-long infatuation with the reductionism of genomics, it is not surprising that both the proteomics knowledge base and tools are assessed as poor to fair. However, even a minor shift in research funding and a renewed challenge to methods developers will rapidly improve the current situation. Adoption of the included &quot;Roadmap&quot; will realistically make the twenty-first century the century of a long-awaited revolution in biology.}, }
@article {pmid30275573, year = {2018}, author = {Gonzalez, A and Navas-Molina, JA and Kosciolek, T and McDonald, D and Vázquez-Baeza, Y and Ackermann, G and DeReus, J and Janssen, S and Swafford, AD and Orchanian, SB and Sanders, JG and Shorenstein, J and Holste, H and Petrus, S and Robbins-Pianka, A and Brislawn, CJ and Wang, M and Rideout, JR and Bolyen, E and Dillon, M and Caporaso, JG and Dorrestein, PC and Knight, R}, title = {Qiita: rapid, web-enabled microbiome meta-analysis.}, journal = {Nature methods}, volume = {15}, number = {10}, pages = {796-798}, pmid = {30275573}, issn = {1548-7105}, support = {R01 HG004872/HG/NHGRI NIH HHS/United States ; R01 HL140976/HL/NHLBI NIH HHS/United States ; R01 MD011389/MD/NIMHD NIH HHS/United States ; }, mesh = {Computational Biology/*methods ; Humans ; *Internet ; *Metagenomics ; *Microbiota ; *Software ; User-Computer Interface ; }, abstract = {Multi-omic insights into microbiome function and composition typically advance one study at a time. However, in order for relationships across studies to be fully understood, data must be aggregated into meta-analyses. This makes it possible to generate new hypotheses by finding features that are reproducible across biospecimens and data layers. Qiita dramatically accelerates such integration tasks in a web-based microbiome-comparison platform, which we demonstrate with Human Microbiome Project and Integrative Human Microbiome Project (iHMP) data.}, }
@article {pmid30269615, year = {2018}, author = {Aziz, RK and Hegazy, SM and Yasser, R and Rizkallah, MR and ElRakaiby, MT}, title = {Drug pharmacomicrobiomics and toxicomicrobiomics: from scattered reports to systematic studies of drug-microbiome interactions.}, journal = {Expert opinion on drug metabolism &amp; toxicology}, volume = {14}, number = {10}, pages = {1043-1055}, doi = {10.1080/17425255.2018.1530216}, pmid = {30269615}, issn = {1744-7607}, mesh = {Animals ; Drug-Related Side Effects and Adverse Reactions/*epidemiology ; Gastrointestinal Microbiome ; Humans ; *Microbiota ; Pharmaceutical Preparations/administration &amp; dosage/*metabolism ; Pharmacogenetics/methods ; Precision Medicine/methods ; Toxicogenetics/methods ; }, abstract = {INTRODUCTION: Pharmacomicrobiomics and toxicomicrobiomics study how variations within the human microbiome (the combination of human-associated microbial communities and their genomes) affect drug disposition, action, and toxicity. These emerging fields, interconnecting microbiology, bioinformatics, systems pharmacology, and toxicology, complement pharmacogenomics and toxicogenomics, expanding the scope of precision medicine. Areas covered: This article reviews some of the most recently reported pharmacomicrobiomic and toxicomicrobiomic interactions. Examples include the impact of the human gut microbiota on cardiovascular drugs, natural products, and chemotherapeutic agents, including immune checkpoint inhibitors. Although the gut microbiota has been the most extensively studied, some key drug-microbiome interactions involve vaginal, intratumoral, and environmental bacteria, and are briefly discussed here. Additionally, computational resources, moving the field from cataloging to predicting interactions, are introduced. Expert opinion: The rapid pace of discovery triggered by the Human Microbiome Project is moving pharmacomicrobiomic research from scattered observations to systematic studies focusing on screening microbiome variants against different drug classes. Better representation of all human populations will improve such studies by avoiding sampling bias, and the integration of multiomic studies with designed experiments will allow establishing causation. In the near future, pharmacomicrobiomic testing is expected to be a key step in screening novel drugs and designing precision therapeutics.}, }
@article {pmid30269123, year = {2018}, author = {Hattori, M}, title = {[Ecology and function of human microbiomes.].}, journal = {Clinical calcium}, volume = {28}, number = {10}, pages = {1398-1405}, doi = {CliCa181013981405}, pmid = {30269123}, issn = {0917-5857}, mesh = {Bacteria ; *Gastrointestinal Microbiome ; High-Throughput Nucleotide Sequencing ; Humans ; Metagenomics ; }, abstract = {Hundreds of trillions of bacteria consisting of ~1,000 species reside in various human body sites to form bacterial communities(microbiomes)specific for the sites. In the past decade, the human microbiome research in the world incredibly advanced by development of a culture-independent metagenomic analysis based on next-generation sequencing technologies. Particularly, current studies have revealed that the human gut microbiome is profoundly associated with the host's health and disease.}, }
@article {pmid30263058, year = {2018}, author = {Maleki Vareki, S and Chanyi, RM and Abdur-Rashid, K and Brennan, L and Burton, JP}, title = {Moving on from Metchnikoff: thinking about microbiome therapeutics in cancer.}, journal = {Ecancermedicalscience}, volume = {12}, number = {}, pages = {867}, pmid = {30263058}, issn = {1754-6605}, abstract = {Precision medicine now needs to also consider the microbiome in oncology treatment. Ingested substances, whether they are a carcinogenic or therapeutic agent, will likely come into contact with the microbiota. Even those delivered extra-intestinally can be influenced beyond xenobiotic metabolism by biochemical factors associated with the microbiota or by an immunological predisposition created by the microbiome. We need to undertake one of the largest paradigm shifts to ever occur in medicine, that is, every drug or ingested substance needs to be re-evaluated for its pharmacological effect post-microbiome interaction. The importance of the microbiome with a focus on the treatment of cancer is discussed. In the near future, it may be possible to specifically manipulate the microbial composition within cancer patients to improve the therapeutic potential of existing oncological agents. However, the current tools to do so are limited. Targeted modulation is likely to be achieved by addition, selective enhancement or depletion of specific microbial types. This may include compounds such as narrow spectrum antimicrobial agents or oligosaccharides that will kill or enhance the bacterial growth of distinct members of the microbiota, respectively. This will stimulate a new era in these fields.}, }
@article {pmid30257907, year = {2019}, author = {Munson, E and Carroll, KC}, title = {An Update on the Novel Genera and Species and Revised Taxonomic Status of Bacterial Organisms Described in 2016 and 2017.}, journal = {Journal of clinical microbiology}, volume = {57}, number = {2}, pages = {}, doi = {10.1128/JCM.01181-18}, pmid = {30257907}, issn = {1098-660X}, abstract = {Recognition and acknowledgment of novel bacterial taxonomy and nomenclature revisions can impact clinical practice, disease epidemiology, and routine clinical microbiology laboratory operations. The Journal of Clinical Microbiology (JCM) herein presents its biannual report summarizing such changes published in the years 2016 and 2017, as published and added by the International Journal of Systematic and Evolutionary Microbiology Noteworthy discussion centers around descriptions of novel Corynebacteriaceae and an anaerobic mycolic acid-producing bacterium in the suborder Corynebacterineae; revisions within the Propionibacterium, Clostridium, Borrelia, and Enterobacter genera; and a major reorganization of the family Enterobacteriaceae. JCM intends to sustain this series of reports as advancements in molecular genetics, whole-genome sequencing, and studies of the human microbiome continue to produce novel taxa and clearer understandings of bacterial relatedness.}, }
@article {pmid30254254, year = {2019}, author = {Nazaroff, WW}, title = {Embracing microbes in exposure science.}, journal = {Journal of exposure science &amp; environmental epidemiology}, volume = {29}, number = {1}, pages = {1-10}, doi = {10.1038/s41370-018-0075-4}, pmid = {30254254}, issn = {1559-064X}, abstract = {Although defined more broadly, exposure science has mainly focused on exposures to environmental chemicals and related stressors, such as airborne particulate matter. There is an opportunity for exposure science to contribute more substantially to improving public health by devoting more attention to microorganisms as key stressors and agents in exposure. The discovery that pathogenic microbes cause disease in humans precipitated a revolution in public health science and disease prevention. With a continued global urgency to address spread of pathogenic microbes, contributions of microorganisms to both infectious and noninfectious processes merit more attention from the exposure science community. Today, discoveries of the importance of the human microbiome as a determinant of health and disease are precipitating a second revolution. Emerging knowledge creates a major opportunity to expand the scope of exposure science to incorporate the human microbiome as a target and modulator of exposure. A study committee of the National Academies of Sciences, Engineering, and Medicine has defined a research strategy to address health risks that pertain to the interaction of environmental chemicals with the human microbiome. Some aspects of this strategy pose important challenges and opportunities for the exposure science community.}, }
@article {pmid30250232, year = {2018}, author = {Zhao, Y and Chen, B and Li, S and Yang, L and Zhu, D and Wang, Y and Wang, H and Wang, T and Shi, B and Gai, Z and Yang, J and Heng, X and Yang, J and Zhang, L}, title = {Detection and characterization of bacterial nucleic acids in culture-negative synovial tissue and fluid samples from rheumatoid arthritis or osteoarthritis patients.}, journal = {Scientific reports}, volume = {8}, number = {1}, pages = {14305}, pmid = {30250232}, issn = {2045-2322}, support = {31471202//Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.)/ ; ZR2014YL040//Natural Science Foundation of Shandong Province (Shandong Provincial Natural Science Foundation)/ ; }, abstract = {Human intestinal microbes can mediate development of arthritis - Studies indicate that certain bacterial nucleic acids may exist in synovial fluid (SF) and could be involved in arthritis, although the underlying mechanism remains unclear. To characterize potential SF bacterial nucleic acids, we used 16S rRNA gene amplicon sequencing to assess bacterial nucleic acid communities in 15 synovial tissue (ST) and 110 SF samples from 125 patients with rheumatoid arthritis (RA) and 16 ST and 42 SF samples from 58 patients with osteoarthritis (OA). Our results showed an abundant diversity of bacterial nucleic acids in these clinical samples, including presence of Porphyromonas and Bacteroides in all 183 samples. Agrobacterium, Comamonas, Kocuria, Meiothermus, and Rhodoplanes were more abundant in synovial tissues of rheumatoid arthritis (STRA). Atopobium, Phascolarctobacterium, Rhodotorula mucilaginosa, Bacteroides uniformis, Rothia, Megasphaera, Turicibacter, Leptotrichia, Haemophilus parainfluenzae, Bacteroides fragilis, Porphyromonas, and Streptococcus were more abundant in synovial tissues of osteoarthritis (STOA). Veillonella dispar, Haemophilus parainfluenzae, Prevotella copri and Treponema amylovorum were more abundant in synovial fluid of rheumatoid arthritis (SFRA), while Bacteroides caccae was more abundant in the synovial fluid of osteoarthritis (SFOA). Overall, this study confirms existence of bacterial nucleic acids in SF and ST samples of RA and OA lesions and reveals potential correlations with degree of disease.}, }
@article {pmid30243649, year = {2018}, author = {Wang, N and Zhu, F and Chen, L and Chen, K}, title = {Proteomics, metabolomics and metagenomics for type 2 diabetes and its complications.}, journal = {Life sciences}, volume = {212}, number = {}, pages = {194-202}, doi = {10.1016/j.lfs.2018.09.035}, pmid = {30243649}, issn = {1879-0631}, mesh = {Animals ; Biomarkers/*analysis ; Diabetes Complications/*diagnosis/genetics/metabolism ; Diabetes Mellitus, Type 2/*diagnosis/genetics/metabolism ; Humans ; Metabolomics/*methods ; Metagenomics/*methods ; Proteomics/*methods ; }, abstract = {Type 2 diabetes mellitus (T2DM) is one of the most common diseases of endocrine and metabolic disorders, whose mechanism is still largely unknown. Fortunately, various &quot;omics&quot; tools have been employed to better understand the progression pathologies of T2DM and its complications. More specifically, proteomics, metabolomics and metagenomics have played crucial roles in advancing deeper understanding of the physiological processes and regulatory mechanisms of T2DM, such as regulation of signaling pathways perturbed by glucose levels, intestinal microorganism, and inflammation and so on. By analyzing the dynamic change and modification of proteins, proteomics has become an important tool in biology and medicine. Metabolomic analysis can amplify and quantify metabolites in living organisms to reveal the relative relationship between metabolites and physiological and pathological changes. There are also increasing evidences that the human microbiome, specifically the gastrointestinal microbiome have a potential role in the etiology and pathological outcomes of T2DM and its complications. This article summarized and discussed the recent applications of these &quot;omics&quot; tools in finding biomarkers for T2DM and its complications. We also reviewed employing multiple &quot;omics&quot; to further advance our understanding of this pathology. This review will benefit deeper understanding in new therapeutic and/or diagnostic biological target for the discovery of T2DM and its complications.}, }
@article {pmid30240894, year = {2019}, author = {Allaband, C and McDonald, D and Vázquez-Baeza, Y and Minich, JJ and Tripathi, A and Brenner, DA and Loomba, R and Smarr, L and Sandborn, WJ and Schnabl, B and Dorrestein, P and Zarrinpar, A and Knight, R}, title = {Microbiome 101: Studying, Analyzing, and Interpreting Gut Microbiome Data for Clinicians.}, journal = {Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association}, volume = {17}, number = {2}, pages = {218-230}, doi = {10.1016/j.cgh.2018.09.017}, pmid = {30240894}, issn = {1542-7714}, support = {K08 DK102902/DK/NIDDK NIH HHS/United States ; }, abstract = {Advances in technical capabilities for reading complex human microbiomes are leading to an explosion of microbiome research, leading in turn to intense interest among clinicians in applying these techniques to their patients. In this review, we discuss the content of the human microbiome, including intersubject and intrasubject variability, considerations of study design including important confounding factors, and different methods in the laboratory and on the computer to read the microbiome and its resulting gene products and metabolites. We highlight several common pitfalls for clinicians, including the expectation that an individual's microbiome will be stable, that diet can induce rapid changes that are large compared with the differences among subjects, that everyone has essentially the same core stool microbiome, and that different laboratory and computational methods will yield essentially the same results. We also highlight the current limitations and future promise of these techniques, with the expectation that an understanding of these considerations will help accelerate the path toward routine clinical application of these techniques developed in research settings.}, }
@article {pmid30240703, year = {2019}, author = {Kyburz, A and Fallegger, A and Zhang, X and Altobelli, A and Artola-Boran, M and Borbet, T and Urban, S and Paul, P and Münz, C and Floess, S and Huehn, J and Cover, TL and Blaser, MJ and Taube, C and Müller, A}, title = {Transmaternal Helicobacter pylori exposure reduces allergic airway inflammation in offspring through regulatory T cells.}, journal = {The Journal of allergy and clinical immunology}, volume = {143}, number = {4}, pages = {1496-1512.e11}, doi = {10.1016/j.jaci.2018.07.046}, pmid = {30240703}, issn = {1097-6825}, support = {TL1 TR001447/TR/NCATS NIH HHS/United States ; P30 CA016087/CA/NCI NIH HHS/United States ; P01 CA116087/CA/NCI NIH HHS/United States ; I01 BX000627/BX/BLRD VA/United States ; R01 AI039657/AI/NIAID NIH HHS/United States ; }, abstract = {BACKGROUND: Transmaternal exposure to tobacco, microbes, nutrients, and other environmental factors shapes the fetal immune system through epigenetic processes. The gastric microbe Helicobacter pylori represents an ancestral constituent of the human microbiota that causes gastric disorders on the one hand and is inversely associated with allergies and chronic inflammatory conditions on the other.<br><br>OBJECTIVE: Here we investigate the consequences of transmaternal exposure to H pylori in utero and/or during lactation for susceptibility to viral and bacterial infection, predisposition to allergic airway inflammation, and development of immune cell populations in the lungs and lymphoid organs.<br><br>METHODS: We use experimental models of house dust mite- or ovalbumin-induced airway inflammation and influenza A virus or Citrobacter rodentium infection along with metagenomics analyses, multicolor flow cytometry, and bisulfite pyrosequencing, to study the effects of H pylori on allergy severity and immunologic and microbiome correlates thereof.<br><br>RESULTS: Perinatal exposure to H pylori extract or its immunomodulator vacuolating cytotoxin confers robust protective effects against allergic airway inflammation not only in first- but also second-generation offspring but does not increase susceptibility to viral or bacterial infection. Immune correlates of allergy protection include skewing of regulatory over effector T cells, expansion of regulatory T-cell subsets expressing CXCR3 or retinoic acid-related orphan receptor γt, and demethylation of the forkhead box P3 (FOXP3) locus. The composition and diversity of the gastrointestinal microbiota is measurably affected by perinatal H pylori exposure.<br><br>CONCLUSION: We conclude that exposure to H pylori has consequences not only for the carrier but also for subsequent generations that can be exploited for interventional purposes.}, }
@article {pmid30230652, year = {2018}, author = {Little, MS and Ervin, SM and Walton, WG and Tripathy, A and Xu, Y and Liu, J and Redinbo, MR}, title = {Active site flexibility revealed in crystal structures of Parabacteroides merdae β-glucuronidase from the human gut microbiome.}, journal = {Protein science : a publication of the Protein Society}, volume = {27}, number = {12}, pages = {2010-2022}, pmid = {30230652}, issn = {1469-896X}, support = {P30 ES010126/ES/NIEHS NIH HHS/United States ; DGS-1650116//National Science Foundation/International ; }, mesh = {Bacteroidaceae/*enzymology ; Catalytic Domain ; Crystallography, X-Ray ; *Gastrointestinal Microbiome ; Glucuronidase/*metabolism ; Humans ; Models, Molecular ; Protein Conformation ; }, abstract = {β-Glucuronidase (GUS) enzymes in the gastrointestinal tract are involved in maintaining mammalian-microbial symbiosis and can play key roles in drug efficacy and toxicity. Parabacteroides merdae GUS was identified as an abundant mini-Loop 2 (mL2) type GUS enzyme in the Human Microbiome Project gut metagenomic database. Here, we report the crystal structure of P. merdae GUS and highlight the differences between this enzyme and extant structures of gut microbial GUS proteins. We find that P. merdae GUS exhibits a distinct tetrameric quaternary structure and that the mL2 motif traces a unique path within the active site, which also includes two arginines distinctive to this GUS. We observe two states of the P. merdae GUS active site; a loop repositions itself by more than 50 Å to place a functionally-relevant residue into the enzyme's catalytic site. Finally, we find that P. merdae GUS is able to bind to homo and heteropolymers of the polysaccharide alginic acid. Together, these data broaden our understanding of the structural and functional diversity in the GUS family of enzymes present in the human gut microbiome and point to specialization as an important feature of microbial GUS orthologs.}, }
@article {pmid30224943, year = {2018}, author = {Randolph, TW and Zhao, S and Copeland, W and Hullar, M and Shojaie, A}, title = {KERNEL-PENALIZED REGRESSION FOR ANALYSIS OF MICROBIOME DATA.}, journal = {The annals of applied statistics}, volume = {12}, number = {1}, pages = {540-566}, pmid = {30224943}, issn = {1932-6157}, support = {K01 HL124050/HL/NHLBI NIH HHS/United States ; P01 CA168530/CA/NCI NIH HHS/United States ; R01 GM114029/GM/NIGMS NIH HHS/United States ; U01 CA162077/CA/NCI NIH HHS/United States ; }, abstract = {The analysis of human microbiome data is often based on dimension-reduced graphical displays and clusterings derived from vectors of microbial abundances in each sample. Common to these ordination methods is the use of biologically motivated definitions of similarity. Principal coordinate analysis, in particular, is often performed using ecologically defined distances, allowing analyses to incorporate context-dependent, non-Euclidean structure. In this paper, we go beyond dimension-reduced ordination methods and describe a framework of high-dimensional regression models that extends these distance-based methods. In particular, we use kernel-based methods to show how to incorporate a variety of extrinsic information, such as phylogeny, into penalized regression models that estimate taxonspecific associations with a phenotype or clinical outcome. Further, we show how this regression framework can be used to address the compositional nature of multivariate predictors comprised of relative abundances; that is, vectors whose entries sum to a constant. We illustrate this approach with several simulations using data from two recent studies on gut and vaginal microbiomes. We conclude with an application to our own data, where we also incorporate a significance test for the estimated coefficients that represent associations between microbial abundance and a percent fat.}, }
@article {pmid30223687, year = {2019}, author = {Lin, H and He, QY and Shi, L and Sleeman, M and Baker, MS and Nice, EC}, title = {Proteomics and the microbiome: pitfalls and potential.}, journal = {Expert review of proteomics}, volume = {16}, number = {6}, pages = {501-511}, doi = {10.1080/14789450.2018.1523724}, pmid = {30223687}, issn = {1744-8387}, abstract = {Introduction: Human symbiotic microbiota are now known to play important roles in human health and disease. Significant progress in our understanding of the human microbiome has been driven by recent technological advances in the fields of genomics, transcriptomics, and proteomics. As a complementary method to metagenomics, proteomics is enabling detailed protein profiling of the microbiome to decipher its structure and function and to analyze its relationship with the human body. Fecal proteomics is being increasingly applied to discover and validate potential health and disease biomarkers, and Therapeutic Goods Administration (TGA)-approved instrumentation and a range of clinical assays are being developed that will collectively play key roles in advancing personalized medicine. Areas covered: This review will introduce the complexity of the microbiome and its role in health and disease (in particular the gastrointestinal tract or gut microbiome), discuss current genomic and proteomic methods for studying this system, including the discovery of potential biomarkers, and outline the development of clinically accepted protocols leading to personalized medicine. Expert commentary: Recognition of the important role the microbiome plays in both health and disease is driving current research in this key area. A proteogenomics approach will be essential to unravel the biologies underlying this complex network.}, }
@article {pmid30218543, year = {2018}, author = {Zhan, X and Xue, L and Zheng, H and Plantinga, A and Wu, MC and Schaid, DJ and Zhao, N and Chen, J}, title = {A small-sample kernel association test for correlated data with application to microbiome association studies.}, journal = {Genetic epidemiology}, volume = {42}, number = {8}, pages = {772-782}, doi = {10.1002/gepi.22160}, pmid = {30218543}, issn = {1098-2272}, support = {GM065450/NH/NIH HHS/United States ; }, mesh = {*Algorithms ; Computer Simulation ; Humans ; Linear Models ; *Microbiota/genetics ; Models, Genetic ; Sample Size ; Twins ; United Kingdom ; }, abstract = {Recent research has highlighted the importance of the human microbiome in many human disease and health conditions. Most current microbiome association analyses focus on unrelated samples; such methods are not appropriate for analysis of data collected from more advanced study designs such as longitudinal and pedigree studies, where outcomes can be correlated. Ignoring such correlations can sometimes lead to suboptimal results or even possibly biased conclusions. Thus, new methods to handle correlated outcome data in microbiome association studies are needed. In this paper, we propose the correlated sequence kernel association test (CSKAT) to address such correlations using the linear mixed model. Specifically, random effects are used to account for the outcome correlations and a variance component test is used to examine the microbiome effect. Compared to existing genetic association tests for longitudinal and family samples, we implement a correction procedure to better calibrate the null distribution of the score test statistic to accommodate the small sample size nature of data collected from a typical microbiome study. Comprehensive simulation studies are conducted to demonstrate the validity and efficiency of our method, and we show that CSKAT achieves a higher power than existing methods while correctly controlling the Type I error rate. We also apply our method to a microbiome data set collected from a UK twin study to illustrate its potential usefulness. A free implementation of our method in R software is available at https://github.com/jchen1981/SSKAT.}, }
@article {pmid30214898, year = {2018}, author = {Trinh, P and Zaneveld, JR and Safranek, S and Rabinowitz, PM}, title = {One Health Relationships Between Human, Animal, and Environmental Microbiomes: A Mini-Review.}, journal = {Frontiers in public health}, volume = {6}, number = {}, pages = {235}, pmid = {30214898}, issn = {2296-2565}, support = {T32 ES015459/ES/NIEHS NIH HHS/United States ; }, abstract = {The One Health concept stresses the ecological relationships between human, animal, and environmental health. Much of the One Health literature to date has examined the transfer of pathogens from animals (e.g., emerging zoonoses) and the environment to humans. The recent rapid development of technology to perform high throughput DNA sequencing has expanded this view to include the study of entire microbial communities. Applying the One Health approach to the microbiome allows for consideration of both pathogenic and non-pathogenic microbial transfer between humans, animals, and the environment. We review recent research studies of such transmission, the molecular and statistical methods being used, and the implications of such microbiome relationships for human health. Our review identified evidence that the environmental microbiome as well as the microbiome of animals in close contact can affect both the human microbiome and human health outcomes. Such microbiome transfer can take place in the household as well as the workplace setting. Urbanization of built environments leads to changes in the environmental microbiome which could be a factor in human health. While affected by environmental exposures, the human microbiome also can modulate the response to environmental factors through effects on metabolic and immune function. Better understanding of these microbiome interactions between humans, animals, and the shared environment will require continued development of improved statistical and ecological modeling approaches. Such enhanced understanding could lead to innovative interventions to prevent and manage a variety of human health and disease states.}, }
@article {pmid30212271, year = {2019}, author = {Ossorio, PN and Zhou, Y}, title = {Regulating stool for microbiota transplantation.}, journal = {Gut microbes}, volume = {10}, number = {2}, pages = {105-108}, doi = {10.1080/19490976.2018.1502537}, pmid = {30212271}, issn = {1949-0984}, mesh = {Fecal Microbiota Transplantation ; Feces ; *Gastrointestinal Microbiome ; Humans ; *Microbiota ; }, abstract = {In 2017 Gut Microbes published &quot;A proposed definition of microbiota transplantation for regulatory purposes,&quot; in which the authors suggest that regulators should draw a line between microbiota transplants and biologic drugs composed of microbial communities (or other products derived from the human microbiome). They develop a definition of microbiota transplantation (MT) to help regulators draw such a line, and suggest that MT need not be, and cannot be, regulated as a biologic drug (a live biotherapeutic product). However, an agency's regulatory scrutiny of a medical product should be commensurate with that product's degree of risk to patients. Products for MT, such as stool, are likely to be as or more dangerous than more highly manipulated microbial products that scientists and regulators agree should be regulated as biologic drugs. Therefore, we argue that MT, as defined by the authors, should receive the same regulatory oversight as any other biologic product intended to cure, mitigate, treat, or prevent disease. We also suggest that regulators might not be able to operationalize the proposed definition of MT.}, }
@article {pmid30211213, year = {2018}, author = {Alves, LF and Westmann, CA and Lovate, GL and de Siqueira, GMV and Borelli, TC and Guazzaroni, ME}, title = {Metagenomic Approaches for Understanding New Concepts in Microbial Science.}, journal = {International journal of genomics}, volume = {2018}, number = {}, pages = {2312987}, pmid = {30211213}, issn = {2314-436X}, abstract = {Over the past thirty years, since the dawn of metagenomic studies, a completely new (micro) universe was revealed, with the potential to have profound impacts on many aspects of the society. Remarkably, the study of human microbiome provided a new perspective on a myriad of human traits previously regarded as solely (epi-) genetically encoded, such as disease susceptibility, immunological response, and social and nutritional behaviors. In this context, metagenomics has established a powerful framework for understanding the intricate connections between human societies and microbial communities, ultimately allowing for the optimization of both human health and productivity. Thus, we have shifted from the old concept of microbes as harmful organisms to a broader panorama, in which the signal of the relationship between humans and microbes is flexible and directly dependent on our own decisions and practices. In parallel, metagenomics has also been playing a major role in the prospection of &quot;hidden&quot; genetic features and the development of biotechnological applications, through the discovery of novel genes, enzymes, pathways, and bioactive molecules with completely new or improved biochemical functions. Therefore, this review highlights the major milestones over the last three decades of metagenomics, providing insights into both its potentialities and current challenges.}, }
@article {pmid30205462, year = {2018}, author = {Hidalgo-Cantabrana, C and Sanozky-Dawes, R and Barrangou, R}, title = {Insights into the Human Virome Using CRISPR Spacers from Microbiomes.}, journal = {Viruses}, volume = {10}, number = {9}, pages = {}, pmid = {30205462}, issn = {1999-4915}, support = {support//North Carolina Agricultural Foundation/International ; internal support//North Carolina State University/International ; }, mesh = {*Biodiversity ; Clustered Regularly Interspaced Short Palindromic Repeats ; Humans ; Metagenomics ; *Microbiota ; Viruses/*classification/genetics/*isolation &amp; purification ; }, abstract = {Due to recent advances in next-generation sequencing over the past decade, our understanding of the human microbiome and its relationship to health and disease has increased dramatically. Yet, our insights into the human virome, and its interplay with important microbes that impact human health, is relatively limited. Prokaryotic and eukaryotic viruses are present throughout the human body, comprising a large and diverse population which influences several niches and impacts our health at various body sites. The presence of prokaryotic viruses like phages, has been documented at many different body sites, with the human gut being the richest ecological niche. Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and associated proteins constitute the adaptive immune system of bacteria, which prevents attack by invasive nucleic acid. CRISPR-Cas systems function by uptake and integration of foreign genetic element sequences into the CRISPR array, which constitutes a genomic archive of iterative vaccination events. Consequently, CRISPR spacers can be investigated to reconstruct interplay between viruses and bacteria, and metagenomic sequencing data can be exploited to provide insights into host-phage interactions within a niche. Here, we show how the CRISPR spacer content of commensal and pathogenic bacteria can be used to determine the evidence of their phage exposure. This framework opens new opportunities for investigating host-virus dynamics in metagenomic data, and highlights the need to dedicate more efforts for virome sampling and sequencing.}, }
@article {pmid30205429, year = {2018}, author = {Hendler, R and Zhang, Y}, title = {Probiotics in the Treatment of Colorectal Cancer.}, journal = {Medicines (Basel, Switzerland)}, volume = {5}, number = {3}, pages = {}, pmid = {30205429}, issn = {2305-6320}, abstract = {The human microbiome plays many roles in inflammation, drug metabolism, and even the development of cancer that we are only beginning to understand. Colorectal cancer has been a focus for study in this field as its pathogenesis and its response to treatment have both been linked to the functioning of microbiota. This literature review evaluates the animal and human studies that have explored this relationship. By manipulating the microbiome with interventions such as probiotic administration, we may be able to reduce colorectal cancer risk and improve the safety and effectiveness of cancer therapy even though additional clinical research is still necessary.}, }
@article {pmid30197908, year = {2017}, author = {Xia, Y and Sun, J}, title = {Hypothesis Testing and Statistical Analysis of Microbiome.}, journal = {Genes &amp; diseases}, volume = {4}, number = {3}, pages = {138-148}, pmid = {30197908}, issn = {2352-4820}, support = {R01 DK105118/DK/NIDDK NIH HHS/United States ; R01 DK114126/DK/NIDDK NIH HHS/United States ; }, abstract = {After the initiation of Human Microbiome Project in 2008, various biostatistic and bioinformatic tools for data analysis and computational methods have been developed and applied to microbiome studies. In this review and perspective, we discuss the research and statistical hypotheses in gut microbiome studies, focusing on mechanistic concepts that underlie the complex relationships among host, microbiome, and environment. We review the current available statistic tools and highlight recent progress of newly developed statistical methods and models. Given the current challenges and limitations in biostatistic approaches and tools, we discuss the future direction in developing statistical methods and models for the microbiome studies.}, }
@article {pmid30196160, year = {2019}, author = {Dong, TS and Gupta, A}, title = {Influence of Early Life, Diet, and the Environment on the Microbiome.}, journal = {Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association}, volume = {17}, number = {2}, pages = {231-242}, doi = {10.1016/j.cgh.2018.08.067}, pmid = {30196160}, issn = {1542-7714}, support = {K23 DK106528/DK/NIDDK NIH HHS/United States ; T32 DK007180/DK/NIDDK NIH HHS/United States ; }, abstract = {Advances in sequencing technology and bioinformatics have greatly enhanced our ability to understand the human microbiome. Over the last decade, a growing body of literature has linked nutrition and the environment to the microbiome and is now thought to be an important contributor to overall health. This paper reviews the literature from the past 10 years to highlight the influence of environmental factors such as diet, early life adversity and stress in shaping and modifying our microbiome towards health and disease. The review shows that many factors such as the mode of delivery, breast milk, stress, diet and medications can greatly influence the development of our gut microbiome and potentially make us more prone to certain diseases. By incorporating environmental factors into models that study the microbiome in the setting of health and disease, may provide a better understanding of disease and potentially new areas of treatment. To highlight this, we will additionally explore the role of the environment and the microbiome in the development of obesity and functional bowel disorders.}, }
@article {pmid30195150, year = {2018}, author = {Sharma, A and Gilbert, JA}, title = {Microbial exposure and human health.}, journal = {Current opinion in microbiology}, volume = {44}, number = {}, pages = {79-87}, doi = {10.1016/j.mib.2018.08.003}, pmid = {30195150}, issn = {1879-0364}, mesh = {Bacteria/classification/genetics/growth &amp; development/isolation &amp; purification ; Fungi/classification/genetics/growth &amp; development/isolation &amp; purification ; *Gastrointestinal Microbiome ; *Health ; Humans ; Immunity ; *Microbiota ; }, abstract = {The human body comprises of micro-ecosystem made up of trillions of microbes (i.e. bacteria, archaea, fungi, protists and viruses). The total microbial gene content, which is referred to as the human microbiome, is fundamental to human physiology and immunity. There exists an intricate relationship between the surrounding microbial world (i.e. the environment) and the endogenous human microbiome, mediated by the immune system. Disrupting this relationship can a profound effect on human health and disease. Understanding how microbial exposure influences immune response and the feedback on endogenous microbial metabolic activity could have profound implications for the development of novel microbial therapeutics. The term 'microbial exposure' is used generally to refer to exogenous environmental microbial interaction, while 'exposome' accounts for both the environmental exposures and the impact of lifestyle-associated microbial impacts, such as diet influences on endogenous microbial metabolism. In this review, we focus on how environment and lifestyle-associated microbial exposures shape the human immune system and microbiome, and how the resulting changes can shape human health, especially during critical developmental windows, that is prenatal, postnatal and adult. We conclude this review by proposing approaches to characterize the microbial exposome so as to accelerate the development of a precision microbial therapeutics for both practical and clinical intervention.}, }
@article {pmid30189627, year = {2018}, author = {Di Francesco, L and Di Girolamo, F and Mennini, M and Masotti, A and Salvatori, G and Rigon, G and Signore, F and Pietrantoni, E and Scapaticci, M and Lante, I and Goffredo, BM and Mazzina, O and Elbousify, AI and Roncada, P and Dotta, A and Fiocchi, A and Putignani, L}, title = {A MALDI-TOF MS Approach for Mammalian, Human, and Formula Milks' Profiling.}, journal = {Nutrients}, volume = {10}, number = {9}, pages = {}, pmid = {30189627}, issn = {2072-6643}, support = {I Fellowship Program//San Camillo Hospital, Treviso, Italy/ ; }, mesh = {Animals ; Camelus ; Equidae ; Food Contamination ; Humans ; Infant ; Infant Formula/*chemistry ; Infant, Newborn ; *Mammals ; Milk/*chemistry ; Milk Proteins/*analysis ; Milk, Human/chemistry ; Multivariate Analysis ; Peptides/*analysis ; Proteomics/*methods ; Ruminants ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/*methods ; }, abstract = {Human milk composition is dynamic, and substitute formulae are intended to mimic its protein content. The purpose of this study was to investigate the potentiality of matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF MS), followed by multivariate data analyses as a tool to analyze the peptide profiles of mammalian, human, and formula milks. Breast milk samples from women at different lactation stages (2 (n = 5), 30 (n = 6), 60 (n = 5), and 90 (n = 4) days postpartum), and milk from donkeys (n = 4), cows (n = 4), buffaloes (n = 7), goats (n = 4), ewes (n = 5), and camels (n = 2) were collected. Different brands (n = 4) of infant formulae were also analyzed. Protein content (<30 kDa) was analyzed by MS, and data were exported for statistical elaborations. The mass spectra for each milk closely clustered together, whereas different milk samples resulted in well-separated mass spectra. Human samples formed a cluster in which colostrum constituted a well-defined subcluster. None of the milk formulae correlated with animal or human milk, although they were specifically characterized and correlated well with each other. These findings propose MALDI-TOF MS milk profiling as an analytical tool to discriminate, in a blinded way, different milk types. As each formula has a distinct specificity, shifting a baby from one to another formula implies a specific proteomic exposure. These profiles may assist in milk proteomics for easiness of use and minimization of costs, suggesting that the MALDI-TOF MS pipelines may be useful for not only milk adulteration assessments but also for the characterization of banked milk specimens in pediatric clinical settings.}, }
@article {pmid30183502, year = {2019}, author = {Strouse, C and Mangalam, A and Zhang, J}, title = {Bugs in the system: bringing the human microbiome to bear in cancer immunotherapy.}, journal = {Gut microbes}, volume = {10}, number = {2}, pages = {109-112}, doi = {10.1080/19490976.2018.1511665}, pmid = {30183502}, issn = {1949-0984}, support = {P30 CA086862/CA/NCI NIH HHS/United States ; P30 ES005605/ES/NIEHS NIH HHS/United States ; }, mesh = {Anti-Bacterial Agents/pharmacology/therapeutic use ; Antibodies, Monoclonal/therapeutic use ; Dysbiosis/immunology/microbiology/therapy ; Fecal Microbiota Transplantation ; Humans ; *Immunotherapy ; Microbiota/drug effects/genetics/*immunology ; Neoplasms/immunology/*microbiology/*therapy ; }, abstract = {The influence of the composition of the human microbiome on the efficacy of cancer directed immunotherapies, such as antibodies directed against the programmed cell death 1 protein (PD-1) or its ligand (PD-L1), has garnered increasing attention as the role of immunotherapies in the care of cancer has grown. Dysbiosis (altered microbiota) has recently been reported to adversely affect the efficacy of cancer directed immunotherapies, and correction of this dysbiosis has the potential to improve the efficacy of these treatments. However, the exact mechanisms underlying this relationship remains unknown. Current methods for characterizing the microbiome likely capture only a small portion of the highly complex interaction between the microbiome and the immune system. Here we discuss the recent reports of the influence of dysbiosis on cancer immunotherapy, methods to more fully characterize the interaction between the microbiome and the immune system, and methods of modulating the immune system to improve the efficacy of cancer immunotherapy.}, }
@article {pmid30181300, year = {2018}, author = {Neil, JA and Cadwell, K}, title = {The Intestinal Virome and Immunity.}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, volume = {201}, number = {6}, pages = {1615-1624}, pmid = {30181300}, issn = {1550-6606}, support = {R01 AI121244/AI/NIAID NIH HHS/United States ; R01 DK093668/DK/NIDDK NIH HHS/United States ; R01 DK103788/DK/NIDDK NIH HHS/United States ; R01 HL123340/HL/NHLBI NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; Gastrointestinal Microbiome/*immunology ; Homeostasis/*immunology ; Humans ; *Intestines/immunology/virology ; Viruses/*immunology ; }, abstract = {The composition of the human microbiome is considered a major source of interindividual variation in immunity and, by extension, susceptibility to diseases. Intestinal bacteria have been the major focus of research. However, diverse communities of viruses that infect microbes and the animal host cohabitate the gastrointestinal tract and collectively constitute the gut virome. Although viruses are typically investigated as pathogens, recent studies highlight a relationship between the host and animal viruses in the gut that is more akin to host-microbiome interactions and includes both beneficial and detrimental outcomes for the host. These viruses are likely sources of immune variation, both locally and extraintestinally. In this review, we describe the components of the gut virome, in particular mammalian viruses, and their ability to modulate host responses during homeostasis and disease.}, }
@article {pmid30180541, year = {2018}, author = {Hill, AB and Beitelshees, M and Nayerhoda, R and Pfeifer, BA and Jones, CH}, title = {Engineering a Next-Generation Glycoconjugate-Like Streptococcus pneumoniae Vaccine.}, journal = {ACS infectious diseases}, volume = {4}, number = {11}, pages = {1553-1563}, doi = {10.1021/acsinfecdis.8b00100}, pmid = {30180541}, issn = {2373-8227}, abstract = {We detail the development of a next-generation Streptococcus pneumoniae liposomal encapsulation of polysaccharides (LEPS) vaccine, with design characteristics geared toward best-in-class efficacy. The first generation LEPS vaccine, which contained 20 encapsulated pneumococcal capsular polysaccharides (CPSs) and two surface-displayed virulence-associated proteins (GlpO and PncO), enabling prophylactic potency against 70+ serotypes of Streptococcus pneumoniae (the causative agent of pneumococcal disease), was rationally redesigned for advanced clinical readiness and best-in-class coverage. In doing so, the virulent-specific GlpO protein antigen was removed from the final formulation due to off-target immunogenicity toward bacterial species within the human microbiome, while directed protection was maintained by increasing the dose of PncO from 17 to 68 μg. LEPS formulation parameters also readily facilitated an increase in CPS valency (to a total of 24) and systematic variation in protein-liposome attachment mechanisms in anticipation of clinical translation. An additional safety assessment study demonstrated that LEPS does not exhibit appreciable toxicological effects even when administered at ten times the effective dose. In summary, this new design offers the broadest, safest, and most-complete protection while maintaining desirable glycoconjugate-like features, positioning the LEPS vaccine platform for clinical success and a global health impact.}, }
@article {pmid30178250, year = {2018}, author = {Riscuta, G and Xi, D and Pierre-Victor, D and Starke-Reed, P and Khalsa, J and Duffy, L}, title = {Diet, Microbiome, and Epigenetics in the Era of Precision Medicine.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {1856}, number = {}, pages = {141-156}, doi = {10.1007/978-1-4939-8751-1_8}, pmid = {30178250}, issn = {1940-6029}, mesh = {Cell Transformation, Neoplastic/genetics/metabolism ; *Diet ; Disease Susceptibility ; Energy Metabolism ; *Epigenesis, Genetic ; Gene Expression Regulation ; Gene-Environment Interaction ; Host-Pathogen Interactions/genetics ; Humans ; *Microbiota ; Neoplasms/diagnosis/etiology/metabolism ; *Precision Medicine/methods ; }, abstract = {Precision medicine is a revolutionary approach to disease prevention and treatment that takes into account individual differences in lifestyle, environment, and biology. The US National Institutes of Health has recently launched The All of Us Research Program (2016) to extend precision medicine to all diseases by building a national research cohort of one million or more US participants. This review is limited to how the human microbiome factors into precision medicine from the applied aspect of preventing and managing cancer. The Precision Medicine Initiative was established in an effort to address particular characteristics of each person with the aim to increase the effectiveness of medical interventions in terms of prevention and treatment of multiple diseases including cancer. Many factors contribute to the response to an intervention. The microbiome and microbially produced metabolites are capable of epigenetic modulation of gene activity, and can influence the response through these mechanisms. The fact that diet has an impact on microbiome implies that it will also affect the epigenetic mechanisms involving microbiota. In this chapter, we review some major epigenetic mechanisms, notably DNA methylation, chromatin remodeling and histone modification, and noncoding RNA, implicated in cancer prevention and treatment. Several examples of how microbially produced metabolites from food influence cancer risk and treatment response through epigenetic mechanisms will be discussed. Some challenges include the limited understanding of how diet shapes the microbiome and how to best evaluate those changes since both, diet and the microbiota, exhibit daily and seasonal variations. Ongoing research seeks to understand the relationship between the human microbiome and multiple diseases including cancer.}, }
@article {pmid30177740, year = {2018}, author = {Lee, JYH and Monk, IR and Gonçalves da Silva, A and Seemann, T and Chua, KYL and Kearns, A and Hill, R and Woodford, N and Bartels, MD and Strommenger, B and Laurent, F and Dodémont, M and Deplano, A and Patel, R and Larsen, AR and Korman, TM and Stinear, TP and Howden, BP}, title = {Global spread of three multidrug-resistant lineages of Staphylococcus epidermidis.}, journal = {Nature microbiology}, volume = {3}, number = {10}, pages = {1175-1185}, doi = {10.1038/s41564-018-0230-7}, pmid = {30177740}, issn = {2058-5276}, support = {R21 AI125870/AI/NIAID NIH HHS/United States ; }, mesh = {Anti-Bacterial Agents/*pharmacology ; Biological Coevolution ; Drug Resistance, Multiple, Bacterial/drug effects/*genetics ; Genes, Bacterial/genetics ; Genome, Bacterial/genetics ; Mutation ; Phylogeny ; Prevalence ; Rifampin/*pharmacology ; Staphylococcal Infections/*epidemiology/microbiology ; Staphylococcus epidermidis/classification/*drug effects/*genetics/isolation &amp; purification ; }, abstract = {Staphylococcus epidermidis is a conspicuous member of the human microbiome, widely present on healthy skin. Here we show that S. epidermidis has also evolved to become a formidable nosocomial pathogen. Using genomics, we reveal that three multidrug-resistant, hospital-adapted lineages of S. epidermidis (two ST2 and one ST23) have emerged in recent decades and spread globally. These lineages are resistant to rifampicin through acquisition of specific rpoB mutations that have become fixed in the populations. Analysis of isolates from 96 institutions in 24 countries identified dual D471E and I527M RpoB substitutions to be the most common cause of rifampicin resistance in S. epidermidis, accounting for 86.6% of mutations. Furthermore, we reveal that the D471E and I527M combination occurs almost exclusively in isolates from the ST2 and ST23 lineages. By breaching lineage-specific DNA methylation restriction modification barriers and then performing site-specific mutagenesis, we show that these rpoB mutations not only confer rifampicin resistance, but also reduce susceptibility to the last-line glycopeptide antibiotics, vancomycin and teicoplanin. Our study has uncovered the previously unrecognized international spread of a near pan-drug-resistant opportunistic pathogen, identifiable by a rifampicin-resistant phenotype. It is possible that hospital practices, such as antibiotic monotherapy utilizing rifampicin-impregnated medical devices, have driven the evolution of this organism, once trivialized as a contaminant, towards potentially incurable infections.}, }
@article {pmid30175072, year = {2018}, author = {Meng, S and Chen, B and Yang, J and Wang, J and Zhu, D and Meng, Q and Zhang, L}, title = {Study of Microbiomes in Aseptically Collected Samples of Human Breast Tissue Using Needle Biopsy and the Potential Role of in situ Tissue Microbiomes for Promoting Malignancy.}, journal = {Frontiers in oncology}, volume = {8}, number = {}, pages = {318}, pmid = {30175072}, issn = {2234-943X}, abstract = {Mounting evidence suggests that changes in microbiome are linked to development of cancer and its aggressiveness. Microbiome profiles in human breast tissue previously presumed to be sterile, have recently been characterized using high-throughput technologies. Recent findings of microbiome variation between benign and malignant disease provides a rationale for exploring microbiomes associated with cancer during tumor progression. We assessed microbiomes of aseptically collected human breast tissue samples in this study, using needle biopsy from patients with benign and malignant tumors of different histological grading, using 16S rRNA gene amplicon sequencing. This is consistent with previous studies, and our results identified distinct microbiome profiles in breast tissues from women with cancer as compared to women with benign breast disease in Chinese cohorts. The enriched microbial biomarkers in malignant tissue included genus Propionicimonas and families Micrococcaceae, Caulobacteraceae, Rhodobacteraceae, Nocardioidaceae, Methylobacteriaceae, which appeared to be ethno-specific. Further, we compared microbiome profiles in malignant tissues of three different histological grades. The relative abundance of family Bacteroidaceae decreased and that of genus Agrococcus increased with the development of malignancy. KEGG pathways inferred by PICRUSt showed that biotin and glycerophospholipid metabolism had significant differences in all three grades. Glycerophospholipid and ribosome biogenesis increased in grade III tissue as compared to grades I and II. Flavonoid biosynthesis significantly decreased in grade III tissue. The specific correlation of these potential microbial biomarkers and indicated pathways with advanced disease could have broad implications in the diagnosis and staging of breast cancer. Further large-cohort investigation of the breast cancer microbiome and its potential mechanism in breast cancer development are essential.}, }
@article {pmid30169121, year = {2018}, author = {Willis-Owen, SAG and Cookson, WOC and Moffatt, MF}, title = {The Genetics and Genomics of Asthma.}, journal = {Annual review of genomics and human genetics}, volume = {19}, number = {}, pages = {223-246}, doi = {10.1146/annurev-genom-083117-021651}, pmid = {30169121}, issn = {1545-293X}, mesh = {Asthma/*genetics ; Cloning, Molecular ; Epigenesis, Genetic ; Genetic Linkage ; *Genetic Predisposition to Disease ; Genome-Wide Association Study ; Humans ; Lung/metabolism ; Transcription, Genetic ; Transcriptome ; }, abstract = {Asthma is a common, clinically heterogeneous disease with strong evidence of heritability. Progress in defining the genetic underpinnings of asthma, however, has been slow and hampered by issues of inconsistency. Recent advances in the tools available for analysis-assaying transcription, sequence variation, and epigenetic marks on a genome-wide scale-have substantially altered this landscape. Applications of such approaches are consistent with heterogeneity at the level of causation and specify patterns of commonality with a wide range of alternative disease traits. Looking beyond the individual as the unit of study, advances in technology have also fostered comprehensive analysis of the human microbiome and its varied roles in health and disease. In this article, we consider the implications of these technological advances for our current understanding of the genetics and genomics of asthma.}, }
@article {pmid30159882, year = {2018}, author = {Skelly, E and Kapellas, K and Cooper, A and Weyrich, LS}, title = {Consequences of colonialism: A microbial perspective to contemporary Indigenous health.}, journal = {American journal of physical anthropology}, volume = {167}, number = {2}, pages = {423-437}, doi = {10.1002/ajpa.23637}, pmid = {30159882}, issn = {1096-8644}, support = {DE150101574//Australian Research Council/International ; }, abstract = {Nearly all Indigenous populations today suffer from worse health than their non-Indigenous counterparts, and despite interventions against known factors, this health &quot;gap&quot; has not improved. The human microbiome-the beneficial, diverse microbial communities that live on and within the human body-is a crucial component in developing and maintaining normal physiological health. Disrupting this ecosystem has repercussions for microbial functionality, and thus, human health. In this article, we propose that modern-day Indigenous population health may suffer from disrupted microbial ecosystems as a consequence of historical colonialism. Colonialism may have interrupted the established relationships between the environment, traditional lifeways, and microbiomes, altering the Indigenous microbiome with detrimental health consequences.}, }
@article {pmid30155556, year = {2019}, author = {Ma, ZS}, title = {Sketching the Human Microbiome Biogeography with DAR (Diversity-Area Relationship) Profiles.}, journal = {Microbial ecology}, volume = {77}, number = {3}, pages = {821-838}, doi = {10.1007/s00248-018-1245-6}, pmid = {30155556}, issn = {1432-184X}, mesh = {Bacteria/classification/genetics/*isolation &amp; purification ; *Biodiversity ; Humans ; Metagenomics ; *Microbiota ; Models, Biological ; }, abstract = {SAR (species area relationship) is a classic ecological theory that has been extensively investigated and applied in the studies of global biogeography and biodiversity conservation in macro-ecology. It has also found important applications in microbial ecology in recent years thanks to the breakthroughs in metagenomic sequencing technology. Nevertheless, SAR has a serious limitation for practical applications-ignoring the species abundance and treating all species as equally abundant. This study aims to explore the biogeography discoveries of human microbiome over 18 sites of 5 major microbiome habitats, establish the baseline DAR (diversity-area scaling relationship) parameters, and perform comparisons with the classic SAR. The extension from SAR to DAR by adopting the Hill numbers as diversity measures not only overcomes the previously mentioned flaw of SAR but also allows for obtaining a series of important findings on the human microbiome biodiversity and biogeography. Specifically, two types of DAR models were built, the traditional power law (PL) and power law with exponential cutoff (PLEC), using comprehensive datasets from the HMP (human microbiome project). Furthermore, the biogeography &quot;maps&quot; for 18 human microbiome sites using their DAR profiles for assessing and predicting the diversity scaling across individuals, PDO profiles (pair-wise diversity overlap) for measuring diversity overlap (similarity), and MAD profile (for predicting the maximal accrual diversity in a population) were sketched out. The baseline biogeography maps for the healthy human microbiome diversity can offer guidelines for conserving human microbiome diversity and investigating the health implications of the human microbiome diversity and heterogeneity.}, }
@article {pmid30154777, year = {2018}, author = {Westerik, N and Reid, G and Sybesma, W and Kort, R}, title = {The Probiotic Lactobacillus rhamnosus for Alleviation of Helicobacter pylori-Associated Gastric Pathology in East Africa.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {1873}, pmid = {30154777}, issn = {1664-302X}, abstract = {The probiotic Lactobacillus rhamnosus GG (LGG) can play a role in establishing a harmless relationship with Helicobacter pylori and reduce gastric pathology in East African populations. H. pylori has the ability to inhabit the surface of the mucous layer of the human stomach and duodenum. In the developing world, an estimated 51% of the population is carrier of H. pylori, while in some Western countries these numbers dropped below 20%, which is probably associated with improved sanitation and smaller family sizes. Colonization by H. pylori can be followed by inflammation of the gastric mucus layer, and is a risk factor in the development of atrophic gastritis, peptic ulcers and gastric cancer. Notwithstanding the higher prevalence of H. pylori carriers in developing countries, no equal overall increase in gastric pathology is found. This has been attributed to a less pro-inflammatory immune response to H. pylori in African compared to Caucasian populations. In addition, a relatively low exposure to other risk factors in certain African populations may play a role, including the use of non-steroidal anti-inflammatory drugs, smoking, and diets without certain protective factors. A novel approach to the reduction of H. pylori associated gastric pathology is found in the administration of the probiotic bacterium Lactobacillus rhamnosus yoba 2012 (LRY), the generic variant of LGG. This gastro-intestinal isolate inhibits H. pylori by competition for substrate and binding sites as well as production of antimicrobial compounds such as lactic acid. In addition, it attenuates the host's H. pylori-induced apoptosis and inflammation responses and stimulates angiogenesis in the gastric and duodenal epithelium. The probiotic LRY is not able to eradicate H. pylori completely, but its co-supplementation in antibiotic eradication therapy has been shown to relieve side effects of this therapy. In Uganda, unlike other African countries, gastric pathology is relatively common, presumably resulting from the lack of dietary protective factors in the traditional diet. Supplementation with LRY through local production of probiotic yogurt, could be a solution to establish a harmless relationship with H. pylori and reduce gastric pathology and subsequent eradication therapy treatment.}, }
@article {pmid30154767, year = {2018}, author = {Kho, ZY and Lal, SK}, title = {The Human Gut Microbiome - A Potential Controller of Wellness and Disease.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {1835}, pmid = {30154767}, issn = {1664-302X}, abstract = {Interest toward the human microbiome, particularly gut microbiome has flourished in recent decades owing to the rapidly advancing sequence-based screening and humanized gnotobiotic model in interrogating the dynamic operations of commensal microbiota. Although this field is still at a very preliminary stage, whereby the functional properties of the complex gut microbiome remain less understood, several promising findings have been documented and exhibit great potential toward revolutionizing disease etiology and medical treatments. In this review, the interactions between gut microbiota and the host have been focused on, to provide an overview of the role of gut microbiota and their unique metabolites in conferring host protection against invading pathogen, regulation of diverse host physiological functions including metabolism, development and homeostasis of immunity and the nervous system. We elaborate on how gut microbial imbalance (dysbiosis) may lead to dysfunction of host machineries, thereby contributing to pathogenesis and/or progression toward a broad spectrum of diseases. Some of the most notable diseases namely Clostridium difficile infection (infectious disease), inflammatory bowel disease (intestinal immune-mediated disease), celiac disease (multisystemic autoimmune disorder), obesity (metabolic disease), colorectal cancer, and autism spectrum disorder (neuropsychiatric disorder) have been discussed and delineated along with recent findings. Novel therapies derived from microbiome studies such as fecal microbiota transplantation, probiotic and prebiotics to target associated diseases have been reviewed to introduce the idea of how certain disease symptoms can be ameliorated through dysbiosis correction, thus revealing a new scientific approach toward disease treatment. Toward the end of this review, several research gaps and limitations have been described along with suggested future studies to overcome the current research lacunae. Despite the ongoing debate on whether gut microbiome plays a role in the above-mentioned diseases, we have in this review, gathered evidence showing a potentially far more complex link beyond the unidirectional cause-and-effect relationship between them.}, }
@article {pmid30150778, year = {2018}, author = {Xu, W and Luo, Z and Alekseyenko, AV and Martin, L and Wan, Z and Ling, B and Qin, Z and Heath, SL and Maas, K and Cong, X and Jiang, W}, title = {Distinct systemic microbiome and microbial translocation are associated with plasma level of anti-CD4 autoantibody in HIV infection.}, journal = {Scientific reports}, volume = {8}, number = {1}, pages = {12863}, pmid = {30150778}, issn = {2045-2322}, support = {P30 AI027767/AI/NIAID NIH HHS/United States ; U54 CA210962/CA/NCI NIH HHS/United States ; R01 AI091526/AI/NIAID NIH HHS/United States ; R01 AI128864/AI/NIAID NIH HHS/United States ; P51 OD011104/OD/NIH HHS/United States ; U54 GM104940/GM/NIGMS NIH HHS/United States ; R01 CA228166/CA/NCI NIH HHS/United States ; R01 LM012517/LM/NLM NIH HHS/United States ; R01 AI093307/AI/NIAID NIH HHS/United States ; P50 AR070591/AR/NIAMS NIH HHS/United States ; R01 NS104016/NS/NINDS NIH HHS/United States ; K23 NR014674/NR/NINR NIH HHS/United States ; R01 CA164964/CA/NCI NIH HHS/United States ; R01 NR016928/NR/NINR NIH HHS/United States ; }, abstract = {Microbial signals have been linked to autoantibody induction. Recently, we found that purified anti-CD4 autoantibodies from the plasma of chronic HIV-1-infected patients under viral-suppressed antiretroviral therapy (ART) play a pathologic role in poor CD4+ T cell recovery. The purpose of the study was to investigate the association of systemic microbiome and anti-CD4 autoantibody production in HIV. Plasma microbiome from 12 healthy controls and 22 HIV-infected subjects under viral-suppressed ART were analyzed by MiSeq sequencing. Plasma level of autoantibodies and microbial translocation (LPS, total bacterial 16S rDNA, soluble CD14, and LPS binding protein) were analyzed by ELISA, limulus amebocyte assay, and qPCR. We found that plasma level of anti-CD4 IgGs but not anti-CD8 IgGs was increased in HIV+ subjects compared to healthy controls. HIV+ subjects with plasma anti-CD4 IgG > 50 ng/mL (high) had reduced microbial diversity compared to HIV+ subjects with anti-CD4 IgG ≤ 50 ng/mL (low). Moreover, plasma anti-CD4 IgG level was associated with elevated microbial translocation and reduced microbial diversity in HIV+ subjects. The Alphaproteobacteria class was significantly enriched in HIV+ subjects with low anti-CD4 IgG compared to patients with high anti-CD4 IgG even after controlling for false discovery rate (FDR). The microbial components were different from the phylum to genus level in HIV+ subjects with high anti-CD4 IgGs compared to the other two groups, but these differences were not significant after controlling for FDR. These results suggest that systemic microbial translocation and microbiome may associate with anti-CD4 autoantibody production in ART-treated HIV disease.}, }
@article {pmid30146515, year = {2018}, author = {Suda, W and Ogata, Y and Nishijima, S}, title = {[Analysis of human microbiome using NGS.].}, journal = {Clinical calcium}, volume = {28}, number = {9}, pages = {1274-1281}, doi = {CliCa180912741281}, pmid = {30146515}, issn = {0917-5857}, mesh = {DNA ; *High-Throughput Nucleotide Sequencing ; Humans ; *Microbiota ; RNA, Ribosomal, 16S ; Sequence Analysis, DNA ; }, abstract = {Recently, next generation sequencers(NGS)became prevalent and enable us possible to comprehensively analyze the entire human microbiome community structures including difficult-to-culture microbes. In this review, we introduce the NGS-based analytical methods of human microbiome, called &quot;meta-16S analysis&quot; and &quot;metagenomic analysis&quot;, then show several fundamental data basing these analyses. Furthermore, we also introduce the importance of database improvement used for analysis and the DNA preparation method from human samples.}, }
@article {pmid30144429, year = {2018}, author = {Friedman, ES and Li, Y and Shen, TD and Jiang, J and Chau, L and Adorini, L and Babakhani, F and Edwards, J and Shapiro, D and Zhao, C and Carr, RM and Bittinger, K and Li, H and Wu, GD}, title = {FXR-Dependent Modulation of the Human Small Intestinal Microbiome by the Bile Acid Derivative Obeticholic Acid.}, journal = {Gastroenterology}, volume = {155}, number = {6}, pages = {1741-1752.e5}, pmid = {30144429}, issn = {1528-0012}, support = {R01 AA026302/AA/NIAAA NIH HHS/United States ; K08 DK106457/DK/NIDDK NIH HHS/United States ; R01 GM123056/GM/NIGMS NIH HHS/United States ; K08 AA021424/AA/NIAAA NIH HHS/United States ; P30 DK050306/DK/NIDDK NIH HHS/United States ; P30 DK019525/DK/NIDDK NIH HHS/United States ; }, mesh = {Adult ; Animals ; Bile Acids and Salts/*physiology ; Chenodeoxycholic Acid/*analogs &amp; derivatives/pharmacokinetics ; Female ; Gastrointestinal Microbiome/*drug effects ; Healthy Volunteers ; Humans ; Intestine, Small/*microbiology ; Male ; Mice ; Mice, Inbred C57BL ; Receptors, Cytoplasmic and Nuclear/*physiology ; }, abstract = {BACKGROUND &amp; AIMS: Intestinal bacteria can modify the composition of bile acids and bile acids, which are regulated by the farnesoid X receptor, affect the survival and growth of gut bacteria. We studied the effects of obeticholic acid (OCA), a bile acid analogue and farnesoid X receptor agonist, on the intestinal microbiomes of humans and mice.<br><br>METHODS: We performed a phase I study in 24 healthy volunteers given OCA (5, 10, or 25 mg/d for 17 days). Fecal and plasma specimens were collected at baseline (day 0) and on days 17 (end of dosing) and 37 (end of study). The fecal specimens were analyzed by shotgun meta-genomic sequencing. A Uniref90 high-stringency genomic analysis was used to assign specific genes to the taxonomic signature of bacteria whose abundance was associated with OCA. Male C57BL/6 mice were gavage fed daily with water, vehicle, or OCA (10 mg/kg) for 2 weeks. Small intestine luminal contents were collected by flushing with saline and fecal pellets were collected at baseline and day 14. Mouse samples were analyzed by 16S-tagged sequencing. Culture experiments were performed to determine the taxonomic-specific effects of bile acids and OCA on bacterial growth.<br><br>RESULTS: Suppression of endogenous bile acid synthesis by OCA in subjects led to a reversible induction of gram-positive bacteria that are found in the small intestine and are components of the diet and oral microbiota. We found that bile acids decreased proliferation of these bacteria in minimum inhibitory concentration assays. In these organisms, there was an increase in the representation of microbial genomic pathways involved in DNA synthesis and amino acid metabolism with OCA treatment of subjects. Consistent with these findings, mice fed OCA had lower endogenous bile acid levels and an increased proportion of Firmicutes, specifically in the small intestine, compared with mice fed water or vehicle.<br><br>CONCLUSIONS: In studying the effects of OCA in humans and mice, we found evidence for interactions between bile acids and features of the small intestinal microbiome. These findings indicate that farnesoid X receptor activation alters the intestinal microbiota and could provide opportunities for microbiome biomarker discovery or new approaches to engineering the human microbiome. ClinicalTrials.gov, NCT01933503.}, }
@article {pmid30135504, year = {2018}, author = {Hoen, AG and Madan, JC and Li, Z and Coker, M and Lundgren, SN and Morrison, HG and Palys, T and Jackson, BP and Sogin, ML and Cottingham, KL and Karagas, MR}, title = {Sex-specific associations of infants' gut microbiome with arsenic exposure in a US population.}, journal = {Scientific reports}, volume = {8}, number = {1}, pages = {12627}, pmid = {30135504}, issn = {2045-2322}, support = {RD-83459901//U.S. Environmental Protection Agency (EPA)/ ; P01ES022832//U.S. Department of Health &amp; Human Services | NIH | National Institute of Environmental Health Sciences (NIEHS)/ ; UH3 OD023275/OD/NIH HHS/United States ; R01LM012723//U.S. Department of Health &amp; Human Services | NIH | U.S. National Library of Medicine (NLM)/ ; R01 GM123014/GM/NIGMS NIH HHS/United States ; P20GM104416//U.S. Department of Health &amp; Human Services | NIH | National Institute of General Medical Sciences (NIGMS)/ ; R01 LM012723/LM/NLM NIH HHS/United States ; K01 LM011985/LM/NLM NIH HHS/United States ; RD-83544201//U.S. Environmental Protection Agency (EPA)/ ; P20 ES018175/ES/NIEHS NIH HHS/United States ; R01GM123014//U.S. Department of Health &amp; Human Services | NIH | National Institute of General Medical Sciences (NIGMS)/ ; P01 ES022832/ES/NIEHS NIH HHS/United States ; UG3 OD023275/OD/NIH HHS/United States ; P20 GM104416/GM/NIGMS NIH HHS/United States ; }, abstract = {Arsenic is a ubiquitous environmental toxicant with antimicrobial properties that can be found in food and drinking water. The influence of arsenic exposure on the composition of the human microbiome in US populations remains unknown, particularly during the vulnerable infant period. We investigated the relationship between arsenic exposure and gut microbiome composition in 204 infants prospectively followed as part of the New Hampshire Birth Cohort Study. Infant urine was analyzed for total arsenic concentration using inductively coupled plasma mass spectrometry. Stool microbiome composition was determined using sequencing of the bacterial 16S rRNA gene. Infant urinary arsenic related to gut microbiome composition at 6 weeks of life (p = 0.05, adjusted for infant feeding type and urine specific gravity). Eight genera, six within the phylum Firmicutes, were enriched with higher arsenic exposure. Fifteen genera were negatively associated with urinary arsenic concentration, including Bacteroides and Bifidobacterium. Upon stratification by both sex and feeding method, we found detectable associations among formula-fed males (p = 0.008), but not other groups (p > 0.05 for formula-fed females and for breastfed males and females). Our findings from a US population indicate that even moderate arsenic exposure may have meaningful, sex-specific effects on the gut microbiome during a critical window of infant development.}, }
@article {pmid30131772, year = {2018}, author = {Ma, Z and Li, L and Li, W}, title = {Assessing and Interpreting the Within-Body Biogeography of Human Microbiome Diversity.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {1619}, pmid = {30131772}, issn = {1664-302X}, abstract = {A human body hosts a relatively independent microbiome including five major regional biomes (i.e., airway, oral, gut, skin, and urogenital). Each of them may possess different regional characteristics with important implications to our health and diseases (i.e., so-termed microbiome associated diseases). Nevertheless, these regional microbiomes are connected with each other through diffusions and migrations. Here, we investigate the within-body (intra-individual) distribution feature of microbiome diversity via diversity area relationship (DAR) modeling, which, to the best of our knowledge, has not been systematically studied previously. We utilized the Hill numbers for measuring alpha and beta-diversities and built 1,200 within-body DAR models with to date the most comprehensive human microbiome datasets of 18 sites from the human microbiome project (HMP) cohort. We established the intra-DAR profile (z-q pattern: the diversity scaling parameter z of the power law (PL) at diversity order q = 0-3), intra-PDO (pair-wise diversity overlap) profile (g-q), and intra-MAD (maximal accrual diversity) profile (Dmax-q) for the within-body biogeography of the human microbiome. These profiles constitute the &quot;maps&quot; of the within-body biogeography, and offer important insights on the within-body distribution of the human microbiome. Furthermore, we investigated the heterogeneity among individuals in their biogeography parameters and found that there is not an &quot;average Joe&quot; that can represent majority of individuals in a cohort or population. For example, we found that most individuals in the HMP cohort have relatively lower maximal accrual diversity (MAD) or in the &quot;long tail&quot; of the so-termed power law distribution. In the meantime, there are a small number of individuals in the cohort who possess disproportionally higher MAD values. These findings may have important implications for personalized medicine of the human microbiome associated diseases in practice, besides their theoretical significance in microbiome research such as establishing the baseline for the conservation of human microbiome.}, }
@article {pmid30129129, year = {2018}, author = {Heerema-McKenney, A}, title = {Defense and infection of the human placenta.}, journal = {APMIS : acta pathologica, microbiologica, et immunologica Scandinavica}, volume = {126}, number = {7}, pages = {570-588}, doi = {10.1111/apm.12847}, pmid = {30129129}, issn = {1600-0463}, mesh = {Communicable Diseases/*pathology ; Female ; Humans ; Placenta/*immunology/*pathology ; Placenta Diseases/*pathology ; Pregnancy ; Pregnancy Complications, Infectious/*pathology ; }, abstract = {The placenta functions as a shield against infection of the fetus. The innate and adaptive immune defenses of the developing fetus are poorly equipped to fight infections. Infection by bacteria, viruses, and protozoa may cause infertility, spontaneous abortion, stillbirth, growth retardation, anomalies of development, premature delivery, neonatal morbidity, and mortality. However, appreciation of the human microbiome and host cell-microbe interactions must be taken into consideration as we try to determine what interactions are pathologic. Infection is typically recognized histologically by the presence of inflammation. Yet, several factors make comparison of the placenta to other human organs difficult. The placenta comprises tissues from two persons, complicating the role of the immune system. The placenta is a temporary organ. It must be eventually expelled; the processes leading to partuition involve maternal inflammation. What is normal or pathologic may be a function of timing or extent of the process. We now must consider whether bacteria, and even some viruses, are useful commensals or pathogens. Still, recognizing infection of the placenta is one of the most important contributions placental pathologic examination can give to care of the mother and neonate. This review provides a brief overview of placental defense against infection, consideration of the placental microbiome, routes of infection, and the histopathology of amniotic fluid infection and TORCH infections.}, }
@article {pmid30129002, year = {2018}, author = {Lin, J and Kimura, BY and Oikarinen, S and Nykter, M}, title = {Bioinformatics Assembling and Assessment of Novel Coxsackievirus B1 Genome.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {1838}, number = {}, pages = {261-272}, doi = {10.1007/978-1-4939-8682-8_18}, pmid = {30129002}, issn = {1940-6029}, mesh = {*Computational Biology/methods ; Enterovirus B, Human/*genetics ; *Genome, Viral ; *Genomics/methods ; Humans ; Metagenome ; Metagenomics/methods/standards ; Quality Control ; }, abstract = {The human microbiome project via application of metagenomic next-generation sequencing techniques has found surprising large and diverse amounts of microbial sequences across different body sites. There is a wave of investigators studying autoimmune related diseases designing from birth case and control studies to elucidate microbial associations and potential direct triggers. Sequencing analysis, considered big data as it typically includes millions of reads, is challenging but particularly demanding and complex is virome profiling due to its lack of pan-viral genomic signature. Impressively thousands of virus complete genomes have been deposited and these high-quality references are core components of virus profiling pipelines and databases. Still it is commonly known that most viral sequences do not map to known viruses. Moreover human viruses, particularly RNA groups, are notoriously heterogeneous due to high mutation rates. Here, we present the related assembling challenges and a series of bioinformatics steps that were applied in the construction of the complete consensus genome of a novel clinical isolate of Coxsackievirus B1. We further demonstrate our effort in calling mutations between prototype Coxsackievirus B1 sequence from GenBank and serial clinical isolate genome grown in cell culture.}, }
@article {pmid30124405, year = {2018}, author = {Dubourg, G and Baron, S and Cadoret, F and Couderc, C and Fournier, PE and Lagier, JC and Raoult, D}, title = {From Culturomics to Clinical Microbiology and Forward.}, journal = {Emerging infectious diseases}, volume = {24}, number = {9}, pages = {1683-1690}, pmid = {30124405}, issn = {1080-6059}, mesh = {Bacteria/classification/genetics/*isolation &amp; purification ; Bacterial Typing Techniques ; Communicable Disease Control ; DNA, Bacterial ; France/epidemiology ; Gram-Negative Bacterial Infections/*epidemiology/microbiology/prevention &amp; control ; Gram-Positive Bacterial Infections/*epidemiology/microbiology/prevention &amp; control ; Humans ; Sensitivity and Specificity ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; }, abstract = {Culturomics has permitted discovery of hundreds of new bacterial species isolated from the human microbiome. Profiles generated by using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry have been added to the mass spectrometer database used in clinical microbiology laboratories. We retrospectively collected raw data from MALDI-TOF mass spectrometry used routinely in our laboratory in Marseille, France, during January 2012-March 2018 and analyzed 16S rDNA sequencing results from misidentified strains. During the study period, 744 species were identified from clinical specimens, of which 21 were species first isolated from culturomics. This collection involved 105 clinical specimens, accounting for 98 patients. In 64 cases, isolation of the bacteria was considered clinically relevant. MALDI-TOF mass spectrometry was able to identify the species in 95.2% of the 105 specimens. While contributing to the extension of the bacterial repertoire associated with humans, culturomics studies also enlarge the spectrum of prokaryotes involved in infectious diseases.}, }
@article {pmid30111623, year = {2018}, author = {Bisanz, JE and Spanogiannopoulos, P and Pieper, LM and Bustion, AE and Turnbaugh, PJ}, title = {How to Determine the Role of the Microbiome in Drug Disposition.}, journal = {Drug metabolism and disposition: the biological fate of chemicals}, volume = {46}, number = {11}, pages = {1588-1595}, doi = {10.1124/dmd.118.083402}, pmid = {30111623}, issn = {1521-009X}, support = {P30 DK098722/DK/NIDDK NIH HHS/United States ; R01 HL122593/HL/NHLBI NIH HHS/United States ; T32 GM007175/GM/NIGMS NIH HHS/United States ; //CIHR/Canada ; }, mesh = {Animals ; Drug Discovery/methods ; Gastrointestinal Microbiome/*physiology ; Humans ; Inactivation, Metabolic/physiology ; Pharmaceutical Preparations/*metabolism ; }, abstract = {With a paradigm shift occurring in health care toward personalized and precision medicine, understanding the numerous environmental factors that impact drug disposition is of paramount importance. The highly diverse and variant nature of the human microbiome is now recognized as a factor driving interindividual variation in therapeutic outcomes. The purpose of this review is to provide a practical guide on methodology that can be applied to study the effects of microbes on the absorption, distribution, metabolism, and excretion of drugs. We also highlight recent examples of how these methods have been successfully applied to help build the basis for researching the intersection of the microbiome and pharmacology. Although in vitro and in vivo preclinical models are highlighted, these methods are also relevant in late-phase drug development or even as a part of routine after-market surveillance. These approaches will aid in filling major knowledge gaps for both current and upcoming therapeutics with the long-term goal of achieving a new type of knowledge-based medicine that integrates data on the host and the microbiome.}, }
@article {pmid30110974, year = {2018}, author = {Fernández, MF and Reina-Pérez, I and Astorga, JM and Rodríguez-Carrillo, A and Plaza-Díaz, J and Fontana, L}, title = {Breast Cancer and Its Relationship with the Microbiota.}, journal = {International journal of environmental research and public health}, volume = {15}, number = {8}, pages = {}, pmid = {30110974}, issn = {1660-4601}, mesh = {Breast Neoplasms/*microbiology ; Dysbiosis ; Estrogens/biosynthesis ; Female ; Gastrointestinal Microbiome/physiology ; Humans ; Microbiota/*physiology ; }, abstract = {The microorganisms that live symbiotically in human beings are increasingly recognized as important players in health and disease. The largest collection of these microorganisms is found in the gastrointestinal tract. Microbial composition reflects both genetic and lifestyle variables of the host. This microbiota is in a dynamic balance with the host, exerting local and distant effects. Microbial perturbation (dysbiosis) could contribute to the risk of developing health problems. Various bacterial genes capable of producing estrogen-metabolizing enzymes have been identified. Accordingly, gut microbiota is capable of modulating estrogen serum levels. Conversely, estrogen-like compounds may promote the proliferation of certain species of bacteria. Therefore, a crosstalk between microbiota and both endogenous hormones and estrogen-like compounds might synergize to provide protection from disease but also to increase the risk of developing hormone-related diseases. Recent research suggests that the microbiota of women with breast cancer differs from that of healthy women, indicating that certain bacteria may be associated with cancer development and with different responses to therapy. In this review, we discuss recent knowledge about the microbiome and breast cancer, identifying specific characteristics of the human microbiome that may serve to develop novel approaches for risk assessment, prevention and treatment for this disease.}, }
@article {pmid30108246, year = {2018}, author = {Bučević Popović, V and Šitum, M and Chow, CT and Chan, LS and Roje, B and Terzić, J}, title = {The urinary microbiome associated with bladder cancer.}, journal = {Scientific reports}, volume = {8}, number = {1}, pages = {12157}, pmid = {30108246}, issn = {2045-2322}, support = {IP-2014-09-1904//Hrvatska Zaklada za Znanost (Croatian Science Foundation)/ ; }, abstract = {Recent findings suggest that human microbiome can influence the development of cancer, but the role of microorganisms in bladder cancer pathogenesis has not been explored yet. The aim of this study was to characterize and compare the urinary microbiome of bladder cancer patients with those of healthy controls. Bacterial communities present in urine specimens collected from 12 male patients diagnosed with bladder cancer, and from 11 healthy, age-matched individuals were analysed using 16S sequencing. Our results show that the most abundant phylum in both groups was Firmicutes, followed by Actinobacteria, Bacteroidetes and Proteobacteria. While microbial diversity and overall microbiome composition were not significantly different between groups, we could identify operational taxonomic units (OTUs) that were more abundant in either group. Among those that were significantly enriched in the bladder cancer group, we identified an OTU belonging to genus Fusobacterium, a possible protumorigenic pathogen. In an independent sample of 42 bladder cancer tissues, 11 had Fusobacterium nucleatum sequences detected by PCR. Three OTUs from genera Veillonella, Streptococcus and Corynebacterium were more abundant in healthy urines. However, due to the limited number of participants additional studies are needed to determine if urinary microbiome is associated with bladder cancer.}, }
@article {pmid30099552, year = {2019}, author = {Bastiaanssen, TFS and Cowan, CSM and Claesson, MJ and Dinan, TG and Cryan, JF}, title = {Making Sense of … the Microbiome in Psychiatry.}, journal = {The international journal of neuropsychopharmacology}, volume = {22}, number = {1}, pages = {37-52}, doi = {10.1093/ijnp/pyy067}, pmid = {30099552}, issn = {1469-5111}, abstract = {Microorganisms can be found almost anywhere, including in and on the human body. The collection of microorganisms associated with a certain location is called a microbiota, with its collective genetic material referred to as the microbiome. The largest population of microorganisms on the human body resides in the gastrointestinal tract; thus, it is not surprising that the most investigated human microbiome is the human gut microbiome. On average, the gut hosts microbes from more than 60 genera and contains more cells than the human body. The human gut microbiome has been shown to influence many aspects of host health, including more recently the brain.Several modes of interaction between the gut and the brain have been discovered, including via the synthesis of metabolites and neurotransmitters, activation of the vagus nerve, and activation of the immune system. A growing body of work is implicating the microbiome in a variety of psychological processes and neuropsychiatric disorders. These include mood and anxiety disorders, neurodevelopmental disorders such as autism spectrum disorder and schizophrenia, and even neurodegenerative disorders such as Alzheimer's and Parkinson's diseases. Moreover, it is probable that most psychotropic medications have an impact on the microbiome.Here, an overview will be provided for the bidirectional role of the microbiome in brain health, age-associated cognitive decline, and neurological and psychiatric disorders. Furthermore, a primer on the common microbiological and bioinformatics techniques used to interrogate the microbiome will be provided. This review is meant to equip the reader with a primer to this exciting research area that is permeating all areas of biological psychiatry research.}, }
@article {pmid30098679, year = {2018}, author = {Kroon, SJ and Ravel, J and Huston, WM}, title = {Cervicovaginal microbiota, women's health, and reproductive outcomes.}, journal = {Fertility and sterility}, volume = {110}, number = {3}, pages = {327-336}, doi = {10.1016/j.fertnstert.2018.06.036}, pmid = {30098679}, issn = {1556-5653}, support = {U19 AI084044/AI/NIAID NIH HHS/United States ; R01 NR014784/NR/NINR NIH HHS/United States ; R01 NR014826/NR/NINR NIH HHS/United States ; R01 NR014784/NR/NINR NIH HHS/United States ; R01 AI116799/AI/NIAID NIH HHS/United States ; }, mesh = {Cervix Uteri/microbiology/*physiology ; Dysbiosis/complications/diagnosis/microbiology ; Female ; Humans ; Infertility, Female/diagnosis/etiology/microbiology ; Lactobacillus/isolation &amp; purification/physiology ; Microbiota/*physiology ; Pregnancy ; Reproduction/*physiology ; Vagina/microbiology/*physiology ; *Women's Health/trends ; }, abstract = {The human microbiome project has shown a remarkable diversity of microbial ecology within the human body. The vaginal microbiota is unique in that in many women it is most often dominated by Lactobacillus species. However, in some women it lacks Lactobacillus spp. and is comprised of a wide array of strict and facultative anaerobes, a state that broadly correlates with increased risk for infection, disease, and poor reproductive and obstetric outcomes. Interestingly, the level of protection against infection can also vary by species and strains of Lactobacillus, and some species although dominant are not always optimal. This factors into the risk of contracting sexually transmitted infections and possibly influences the occurrence of resultant adverse reproductive outcomes such as tubal factor infertility. The composition and function of the vaginal microbiota appear to play an important role in pregnancy and fertility treatment outcomes and future research in this field will shed further translational mechanistic understanding onto the interplay of the vaginal microbiota with women's health and reproduction.}, }
@article {pmid30082394, year = {2018}, author = {Shrivastava, A and Patel, VK and Tang, Y and Yost, SC and Dewhirst, FE and Berg, HC}, title = {Cargo transport shapes the spatial organization of a microbial community.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {34}, pages = {8633-8638}, pmid = {30082394}, issn = {1091-6490}, support = {K99 DE026826/DE/NIDCR NIH HHS/United States ; R01 AI016478/AI/NIAID NIH HHS/United States ; R37 DE016937/DE/NIDCR NIH HHS/United States ; }, mesh = {Capnocytophaga/*physiology ; Humans ; Microbial Consortia/*physiology ; Microbiota/*physiology ; Mouth/*microbiology ; }, abstract = {The human microbiome is an assemblage of diverse bacteria that interact with one another to form communities. Bacteria in a given community are arranged in a 3D matrix with many degrees of freedom. Snapshots of the community display well-defined structures, but the steps required for their assembly are not understood. Here, we show that this construction is carried out with the help of gliding bacteria. Gliding is defined as the motion of cells over a solid or semisolid surface without the necessity of growth or the aid of pili or flagella. Genomic analysis suggests that gliding bacteria are present in human microbial communities. We focus on Capnocytophaga gingivalis, which is present in abundance in the human oral microbiome. Tracking of fluorescently labeled single cells and of gas bubbles carried by fluid flow shows that swarms of C. gingivalis are layered, with cells in the upper layers moving more rapidly than those in the lower layers. Thus, cells also glide on top of one another. Cells of nonmotile bacterial species attach to the surface of C. gingivalis and are propelled as cargo. The cargo cell moves along the length of a C. gingivalis cell, looping from one pole to the other. Multicolor fluorescent spectral imaging of cells of different live but nonmotile bacterial species reveals their long-range transport in a polymicrobial community. A swarm of C. gingivalis transports some nonmotile bacterial species more efficiently than others and helps to shape the spatial organization of a polymicrobial community.}, }
@article {pmid30078138, year = {2018}, author = {Martin, TC and Visconti, A and Spector, TD and Falchi, M}, title = {Conducting metagenomic studies in microbiology and clinical research.}, journal = {Applied microbiology and biotechnology}, volume = {102}, number = {20}, pages = {8629-8646}, pmid = {30078138}, issn = {1432-0614}, support = {//Wellcome Trust/United Kingdom ; }, mesh = {Bacteria/classification/genetics/*isolation &amp; purification ; Bacterial Infections/*microbiology ; Clinical Protocols ; High-Throughput Nucleotide Sequencing ; Humans ; *Metagenomics/methods ; Microbiology ; }, abstract = {Owing to the increased cost-effectiveness of high-throughput technologies, the number of studies focusing on the human microbiome and its connections to human health and disease has recently surged. However, best practices in microbiology and clinical research have yet to be clearly established. Here, we present an overview of the challenges and opportunities involved in conducting a metagenomic study, with a particular focus on data processing and analytical methods.}, }
@article {pmid30074108, year = {2019}, author = {Bicknell, B and Liebert, A and Johnstone, D and Kiat, H}, title = {Photobiomodulation of the microbiome: implications for metabolic and inflammatory diseases.}, journal = {Lasers in medical science}, volume = {34}, number = {2}, pages = {317-327}, doi = {10.1007/s10103-018-2594-6}, pmid = {30074108}, issn = {1435-604X}, mesh = {Animals ; Feces/microbiology ; Humans ; Inflammation/*radiotherapy ; *Low-Level Light Therapy ; Male ; Metabolic Diseases/*radiotherapy ; Mice, Inbred BALB C ; Microbiota/genetics/*radiation effects ; Phylogeny ; Principal Component Analysis ; RNA, Ribosomal, 16S/genetics ; }, abstract = {The human microbiome is intimately associated with human health, with a role in obesity, metabolic diseases such as type 2 diabetes, and divergent diseases such as cardiovascular and neurodegenerative diseases. The microbiome can be changed by diet, probiotics, and faecal transplants, which has flow-on effects to health outcomes. Photobiomodulation has a therapeutic effect on inflammation and neurological disorders (amongst others) and has been reported to influence metabolic disorders and obesity. The aim of this study was to examine the possibility that PBM could influence the microbiome of mice. Mice had their abdomen irradiated with red (660 nm) or infrared (808 nm) low-level laser, either as single or multiple doses, over a 2-week period. Genomic DNA extracted from faecal pellets was pyrosequenced for the 16S rRNA gene. There was a significant (p < 0.05) difference in microbial diversity between PBM- and sham-treated mice. One genus of bacterium (Allobaculum) significantly increased (p < 0.001) after infrared (but not red light) PBM by day 14. Despite being a preliminary trial with small experimental numbers, we have demonstrated for the first time that PBM can alter microbiome diversity in healthy mice and increase numbers of Allobaculum, a bacterium associated with a healthy microbiome. This change is most probably a result of PBMt affecting the host, which in turn influenced the microbiome. If this is confirmed in humans, the possibility exists for PBMt to be used as an adjunct therapy in treatment of obesity and other lifestyle-related disorders, as well as cardiovascular and neurodegenerative diseases. The clinical implications of altering the microbiome using PBM warrants further investigation.}, }
@article {pmid30071492, year = {2018}, author = {Hanssen, EN and Liland, KH and Gill, P and Snipen, L}, title = {Optimizing body fluid recognition from microbial taxonomic profiles.}, journal = {Forensic science international. Genetics}, volume = {37}, number = {}, pages = {13-20}, doi = {10.1016/j.fsigen.2018.07.012}, pmid = {30071492}, issn = {1878-0326}, mesh = {Bacteria/*genetics ; Discriminant Analysis ; Feces/*microbiology ; Female ; Forensic Genetics/methods ; High-Throughput Nucleotide Sequencing ; Humans ; Least-Squares Analysis ; Microbiota ; Mouth/*microbiology ; Nasal Cavity/*microbiology ; *RNA, Ribosomal, 16S ; Sensitivity and Specificity ; Sequence Analysis, DNA ; Skin/*microbiology ; Vagina/*microbiology ; }, abstract = {In forensics the DNA-profile is used to identify the person who left a biological trace, but information on body fluid can also be essential in the evidence evaluation process. Microbial composition data could potentially be used for body fluid recognition as an improved alternative to the currently used presumptive tests. We have developed a customized workflow for interpretation of bacterial 16S sequence data based on a model composed of Partial Least Squares (PLS) in combination with Linear Discriminant Analysis (LDA). Large data sets from the Human Microbiome Project (HMP) and the American Gut Project (AGP) were used to test different settings in order to optimize performance. From the initial cross-validation of body fluid recognition within the HMP data, the optimal overall accuracy was close to 98%. Sensitivity values for the fecal and oral samples were ≥0.99, followed by the vaginal samples with 0.98 and the skin and nasal samples with 0.96 and 0.81 respectively. Specificity values were high for all 5 categories, mostly >0.99. This optimal performance was achieved by using the following settings: Taxonomic profiles based on operational taxonomic units (OTUs) with 0.98 identity (OTU98), Aitchisons simplex transform with C = 1 pseudo-count and no regularization (r = 1) in the PLS step. Variable selection did not improve the performance further. To test for robustness across sequencing platforms, we also trained the classifier on HMP data and tested on the AGP data set. In this case, the standard OTU based approach showed moderately decline in accuracy. However, by using taxonomic profiles made by direct assignment of reads to a genus, we were able to nearly maintain the high accuracy levels. The optimal combination of settings was still used, except the taxonomic level being genus instead of OTU98. The performance may be improved even further by using higher resolution taxonomic bins.}, }
@article {pmid30069974, year = {2018}, author = {Mert, I and Walther-Antonio, M and Mariani, A}, title = {Case for a role of the microbiome in gynecologic cancers: Clinician's perspective.}, journal = {The journal of obstetrics and gynaecology research}, volume = {44}, number = {9}, pages = {1693-1704}, doi = {10.1111/jog.13701}, pmid = {30069974}, issn = {1447-0756}, support = {P50 CA136393/CA/NCI NIH HHS/United States ; }, mesh = {Dysbiosis/*complications ; Endometrial Neoplasms/*etiology ; Female ; Humans ; *Microbiota ; Ovarian Neoplasms/*etiology ; }, abstract = {In this review, we aimed to provide insight into the microbiome and its association with endometrial and ovarian cancer and their risk factors. We reviewed the literature focusing on the relationship between the microbiome and cancer, as well as the relationship between gynecologic diseases and cancers. The human body contains different kinds of microorganisms in various body parts, which is termed the microbiome. The number of microorganisms that live in and on the human body is greater than that of the human germ and somatic cells by 10-fold. The relationship between a human and their microbiome is complex; it is also one of the most important components of homeostasis. Impairment of microbiome-host homeostasis has been associated with obesity, several cancers, preterm labor, inflammatory and allergic conditions and neurodevelopmental disorders. Direct and strong causal relationships have been established for several cancers and microorganisms, such as gastric lymphoma and Helicobacter pylori infection. Interestingly, eradication of the infectious agents has also been shown to be therapeutic. The association between cancer and the microbiome, however, is more complicated than a 1 bacteria-1 cancer model, and a shift in a healthy microbiome can result in various cancers via inflammation, change in microenvironment or DNA-damaging toxins. The human microbiome is an integral part of homeostasis. Understanding the mechanisms that cause dysbiosis will enable us to elucidate the pathways that result in malignancy and investigate new treatment modalities.}, }
@article {pmid30066739, year = {2018}, author = {Costa, AN and Costa, FMD and Campos, SV and Salles, RK and Athanazio, RA}, title = {The pulmonary microbiome: challenges of a new paradigm.}, journal = {Jornal brasileiro de pneumologia : publicacao oficial da Sociedade Brasileira de Pneumologia e Tisilogia}, volume = {44}, number = {5}, pages = {424-432}, doi = {10.1590/S1806-37562017000000209}, pmid = {30066739}, issn = {1806-3756}, mesh = {Dysbiosis/*immunology ; Humans ; Immune System/*microbiology ; Lung/*microbiology ; Lung Diseases/*microbiology ; Microbiota/*physiology ; }, abstract = {The study of the human microbiome-and, more recently, that of the respiratory system-by means of sophisticated molecular biology techniques, has revealed the immense diversity of microbial colonization in humans, in human health, and in various diseases. Apparently, contrary to what has been believed, there can be nonpathogenic colonization of the lungs by microorganisms such as bacteria, fungi, and viruses. Although this physiological lung microbiome presents low colony density, it presents high diversity. However, some pathological conditions lead to a loss of that diversity, with increasing concentrations of some bacterial genera, to the detriment of others. Although we possess qualitative knowledge of the bacteria present in the lungs in different states of health or disease, that knowledge has advanced to an understanding of the interaction of this microbiota with the local and systemic immune systems, through which it modulates the immune response. Given this intrinsic relationship between the microbiota and the lungs, studies have put forth new concepts about the pathophysiological mechanisms of homeostasis in the respiratory system and the potential dysbiosis in some diseases, such as cystic fibrosis, COPD, asthma, and interstitial lung disease. This departure from the paradigm regarding knowledge of the lung microbiota has made it imperative to improve understanding of the role of the microbiome, in order to identify possible therapeutic targets and to develop innovative clinical approaches. Through this new leap of knowledge, the results of preliminary studies could translate to benefits for our patients.}, }
@article {pmid30058389, year = {2018}, author = {Greco, V and Piras, C and Pieroni, L and Ronci, M and Putignani, L and Roncada, P and Urbani, A}, title = {Applications of MALDI-TOF mass spectrometry in clinical proteomics.}, journal = {Expert review of proteomics}, volume = {15}, number = {8}, pages = {683-696}, doi = {10.1080/14789450.2018.1505510}, pmid = {30058389}, issn = {1744-8387}, mesh = {Body Fluids/metabolism ; Drug Discovery ; Humans ; Neoplasm, Residual/metabolism ; *Proteomics ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/*methods ; }, abstract = {INTRODUCTION: The development of precision medicine requires advanced technologies to address the multifactorial disease stratification and to support personalized treatments. Among omics techniques, proteomics based on Mass Spectrometry (MS) is becoming increasingly relevant in clinical practice allowing a phenotypic characterization of the dynamic functional status of the organism. From this perspective, Matrix Assisted Laser Desorption Ionization Time of Flight (MALDI-TOF) MS is a suitable platform for providing a high-throughput support to clinics. Areas covered: This review aims to provide an updated overview of MALDI-TOF MS applications in clinical proteomics. The most relevant features of this analysis have been discussed, highlighting both pre-analytical and analytical factors that are crucial in proteomics studies. Particular emphasis is placed on biofluids proteomics for biomarkers discovery and on recent progresses in clinical microbiology, drug monitoring, and minimal residual disease (MRD). Expert commentary: Despite some analytical limitations, the latest technological advances together with the easiness of use, the low time and low cost consuming and the high throughput are making MALDI-TOF MS instruments very attractive for the clinical practice. These features offer a significant potential for the routine of the clinical laboratory and ultimately for personalized medicine.}, }
@article {pmid30056862, year = {2018}, author = {Rosa, CP and Brancaglion, GA and Miyauchi-Tavares, TM and Corsetti, PP and de Almeida, LA}, title = {Antibiotic-induced dysbiosis effects on the murine gastrointestinal tract and their systemic repercussions.}, journal = {Life sciences}, volume = {207}, number = {}, pages = {480-491}, doi = {10.1016/j.lfs.2018.06.030}, pmid = {30056862}, issn = {1879-0631}, mesh = {Animals ; Anti-Bacterial Agents/*adverse effects ; Cytokines/metabolism ; Disease Models, Animal ; Dysbiosis/*drug therapy ; Fatty Acids, Volatile/chemistry ; Gastrointestinal Microbiome/*drug effects ; Gastrointestinal Tract/*drug effects/microbiology ; Homeostasis ; Humans ; Inflammation ; Mice ; T-Lymphocyte Subsets ; T-Lymphocytes/cytology ; }, abstract = {The gastrointestinal tract has become a focus of study recently. The crosstalk between microbiota, especially bacteria, and the intestinal mucosa has to be accurately balanced in order to maintain physiological homeostasis in the human body. This dynamic interaction results in different levels of short-chain fatty acids (SCFAs), IgA, and T cell lymphocyte subsets, which could lead the human body towards health or disease. The disruption of this microbiome characterises gut dysbiosis. Antibiotics are usually prescribed to fight against bacterial infection. They can also modulate the human microbiome, since it acts directly over organisational taxonomic units (OTUs) when taken orally. As a result, these pharmaceuticals enable gut dysbiosis and its systemic effects due to microbiome disturbance. Here, current data have been gathered from mice model experiments and epidemiological studies in an antibiotic-centred perspective. The presented data suggest the importance of translational studies in a murine model focusing on GIT homeostasis with bacterial groups since any changes to the GIT-microbiota have systemic repercussions in human health and disease.}, }
@article {pmid30052903, year = {2018}, author = {Frey, AM and Ansbro, K and Kamble, NS and Pham, TK and Stafford, GP}, title = {Characterisation and pure culture of putative health-associated oral bacterium BU063 (Tannerella sp. HOT-286) reveals presence of a potentially novel glycosylated S-layer.}, journal = {FEMS microbiology letters}, volume = {365}, number = {17}, pages = {}, doi = {10.1093/femsle/fny180}, pmid = {30052903}, issn = {1574-6968}, support = {BB/K501098/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, abstract = {Tannerella HOT-286 (phylotype BU063) is a recently identified novel filamentous Gram-negative anaerobic oral bacterium cultured for the first time recently in co-culture with Propionibacterium acnes. In contrast to the related periodontal disease-associated pathobiont Tannerella forsythia, it is considered a putative health-associated bacterium. In this paper, we identified that this organism could be grown in pure culture if N-acetyl muramic acid (NAM) was provided in the media, although surprisingly the genetic basis of this phenomenon is not likely to be due to a lack of NAM synthesis genes. During further microbiological investigations, we showed for the first time that T. HOT-286 possesses a prominent extracellular S-layer with a novel morphology putatively made up of two proteins modified with an unknown glycan. These data further our knowledge of this poorly understood organism and genus that is an important part of the oral and human microbiome.}, }
@article {pmid30052094, year = {2018}, author = {Laing, B and Barnett, MPG and Marlow, G and Nasef, NA and Ferguson, LR}, title = {An update on the role of gut microbiota in chronic inflammatory diseases, and potential therapeutic targets.}, journal = {Expert review of gastroenterology &amp; hepatology}, volume = {12}, number = {10}, pages = {969-983}, doi = {10.1080/17474124.2018.1505497}, pmid = {30052094}, issn = {1747-4132}, mesh = {Age Factors ; Diet ; Dysbiosis/*complications/*therapy ; Environment ; Exercise ; Fatty Acids, Volatile/metabolism ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/genetics/immunology/*physiology ; Humans ; Inflammation/*microbiology ; Intestinal Mucosa/immunology/*physiology ; Probiotics/therapeutic use ; }, abstract = {INTRODUCTION: The human microbiome plays a critical role in human health, having metabolic, protective, and trophic functions, depending upon its' exact composition. This composition is affected by a number of factors, including the genetic background of the individual, early life factors (including method of birth, length of breastfeeding) and nature of the diet and other environmental exposures (including cigarette smoking) and general life habits. It plays a key role in the control of inflammation, and in turn, its' composition is significantly influenced by inflammation. Areas covered: We consider metabolic, protective, and trophic functions of the microbiome and influences through the lifespan from post-partum effects, to diet later in life in healthy older adults, the effects of aging on both its' composition, and influence on health and potential therapeutic targets that may have anti-inflammatory effects. Expert commentary: The future will see the growth of more effective therapies targeting the microbiome particularly with respect to the use of specific nutrients and diets personalized to the individual.}, }
@article {pmid30042747, year = {2018}, author = {Westerik, N and Kort, R and Sybesma, W and Reid, G}, title = {Lactobacillus rhamnosus Probiotic Food as a Tool for Empowerment Across the Value Chain in Africa.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {1501}, pmid = {30042747}, issn = {1664-302X}, abstract = {Perhaps by serendipity, but Lactobacillus rhamnosus has emerged from the 1980s as the most researched probiotic species. The many attributes of the two main probiotic strains of the species, L. rhamnosus GG and GR-1, have made them suitable for applications to developing countries in Africa and beyond. Their use with a Streptococcus thermophilus starter strain C106, in the fermentation of milk, millet, and juices has provided a means to reach over 250,000 consumers of the first probiotic food on the continent. The social and economical implications for this translational research are significant, and especially pertinent for people living in poverty, with malnutrition and exposure to environmental toxins and infectious diseases including HIV and malaria. This example of probiotic applications illustrates the power of microbes in positively impacting the lives of women, men, and children, right across the food value chain.}, }
@article {pmid30039798, year = {2018}, author = {Zhang, XS and Li, J and Krautkramer, KA and Badri, M and Battaglia, T and Borbet, TC and Koh, H and Ng, S and Sibley, RA and Li, Y and Pathmasiri, W and Jindal, S and Shields-Cutler, RR and Hillmann, B and Al-Ghalith, GA and Ruiz, VE and Livanos, A and van 't Wout, AB and Nagalingam, N and Rogers, AB and Sumner, SJ and Knights, D and Denu, JM and Li, H and Ruggles, KV and Bonneau, R and Williamson, RA and Rauch, M and Blaser, MJ}, title = {Antibiotic-induced acceleration of type 1 diabetes alters maturation of innate intestinal immunity.}, journal = {eLife}, volume = {7}, number = {}, pages = {}, pmid = {30039798}, issn = {2050-084X}, support = {T35 DK007421/DK/NIDDK NIH HHS/United States ; R01 DK110014/DK/NIDDK NIH HHS/United States ; R01DK110014/NH/NIH HHS/United States ; T32 GM008692/GM/NIGMS NIH HHS/United States ; T32 GM007308/GM/NIGMS NIH HHS/United States ; 5T35DK007421/NH/NIH HHS/United States ; F30 DK108494/DK/NIDDK NIH HHS/United States ; R37GM059785/NH/NIH HHS/United States ; 15-A0-00-00-0039-29-01//Janssen Research and Development/International ; -33.17CVD01//Fondation Leducq/International ; R37 GM059785/GM/NIGMS NIH HHS/United States ; F30DK108494/NH/NIH HHS/United States ; 15-A0-00-00-0039-29-01//Janssen Labs London/International ; }, mesh = {Adaptive Immunity/drug effects ; Animals ; Anti-Bacterial Agents/*adverse effects/immunology ; Diabetes Mellitus, Type 1/*immunology/microbiology/pathology ; Female ; Gastrointestinal Microbiome/drug effects/*immunology ; Ileum/immunology/microbiology ; Immunity, Innate/*drug effects/immunology ; Intestines/microbiology ; Mice ; Mice, Inbred NOD ; Microbiota/drug effects/immunology ; }, abstract = {The early-life intestinal microbiota plays a key role in shaping host immune system development. We found that a single early-life antibiotic course (1PAT) accelerated type 1 diabetes (T1D) development in male NOD mice. The single course had deep and persistent effects on the intestinal microbiome, leading to altered cecal, hepatic, and serum metabolites. The exposure elicited sex-specific effects on chromatin states in the ileum and liver and perturbed ileal gene expression, altering normal maturational patterns. The global signature changes included specific genes controlling both innate and adaptive immunity. Microbiome analysis revealed four taxa each that potentially protect against or accelerate T1D onset, that were linked in a network model to specific differences in ileal gene expression. This simplified animal model reveals multiple potential pathways to understand pathogenesis by which early-life gut microbiome perturbations alter a global suite of intestinal responses, contributing to the accelerated and enhanced T1D development.}, }
@article {pmid30021103, year = {2018}, author = {Proal, AD and Marshall, TG}, title = {Re-framing the theory of autoimmunity in the era of the microbiome: persistent pathogens, autoantibodies, and molecular mimicry.}, journal = {Discovery medicine}, volume = {25}, number = {140}, pages = {299-308}, pmid = {30021103}, issn = {1944-7930}, mesh = {Autoantibodies/*immunology ; *Autoimmunity ; Dysbiosis/immunology/microbiology ; Humans ; *Microbiota ; *Models, Immunological ; Molecular Mimicry/*immunology ; }, abstract = {The theory of autoimmunity was developed at a time when the human body was regarded as largely sterile. Antibodies in patients with chronic inflammatory disease could consequently not be tied to persistent human pathogens. The concept of the &quot;autoantibody&quot; was created to reconcile this phenomenon. Today, however, the discovery of the human microbiome has revolutionized our understanding of human biology. Humans are superorganisms that harbor trillions of persistent microbial cells. Indeed, vast human microbiomes have been detected in human tissue and blood. These microbial ecosystems harbor thousands of newly identified bacteria, viruses, and other microorganisms -- most of which can act as pathogens under conditions of immunosuppression. The theory of autoimmunity must be revised to account for the human microbiome. Here, we propose a model in which &quot;autoantibodies&quot; are created in response to chronic, persistent microbiome pathogens. The structural homology (molecular mimicry) between pathogen and host proteins can result in &quot;collateral damage&quot; to surrounding human tissue. This calls for a paradigm shift in autoimmune disease treatment. Immunosuppressive medications palliate inflammatory symptoms at the expense of microbiome health and balance. In contrast, treatments that support the immune system in autoimmune disease could allow patients to target pathogens at the root of the disease process.}, }
@article {pmid30019906, year = {2018}, author = {Wang, AY and Thuy-Boun, PS and Stupp, GS and Su, AI and Wolan, DW}, title = {Triflic Acid Treatment Enables LC-MS/MS Analysis of Insoluble Bacterial Biomass.}, journal = {Journal of proteome research}, volume = {17}, number = {9}, pages = {2978-2986}, doi = {10.1021/acs.jproteome.8b00166}, pmid = {30019906}, issn = {1535-3907}, support = {U54 GM114833/GM/NIGMS NIH HHS/United States ; }, mesh = {Bacillus subtilis/*chemistry/genetics/metabolism ; Bacterial Proteins/*isolation &amp; purification ; Chromatography, Liquid ; Complex Mixtures/chemistry ; Gastrointestinal Microbiome/genetics ; Humans ; Jurkat Cells ; Membrane Proteins/*isolation &amp; purification ; Mesylates/*chemistry ; Metagenome ; Proteomics/*methods ; Pseudomonas aeruginosa/*chemistry/genetics/metabolism ; Sonication/methods ; Tandem Mass Spectrometry ; }, abstract = {The lysis and extraction of soluble bacterial proteins from cells is a common practice for proteomics analyses, but insoluble bacterial biomasses are often left behind. Here, we show that with triflic acid treatment, the insoluble bacterial biomass of Gram- and Gram+ bacteria can be rendered soluble. We use LC-MS/MS shotgun proteomics to show that bacterial proteins in the soluble and insoluble postlysis fractions differ significantly. Additionally, in the case of Gram- Pseudomonas aeruginosa, triflic acid treatment enables the enrichment of cell-envelope-associated proteins. Finally, we apply triflic acid to a human microbiome sample to show that this treatment is robust and enables the identification of a new, complementary subset of proteins from a complex microbial mixture.}, }
@article {pmid30017599, year = {2018}, author = {Chanyi, RM and Alzubaidi, R and Leung, EJY and Wilcox, HB and Brock, GB and Burton, JP}, title = {Inflatable Penile Prostheses Implantation: Does Antibiotic Exposure Matter?.}, journal = {Sexual medicine}, volume = {6}, number = {3}, pages = {248-254}, pmid = {30017599}, issn = {2050-1161}, abstract = {BACKGROUND: Inflatable penile prosthetic (IPP) infections are unusual but carry high patient morbidity and healthcare costs.<br><br>AIM: To increase the bactericidal effect of IPP tubing material to prevent future bacterial infections and to determine whether this effect is time-dependent.<br><br>METHODS: A modified disk diffusion assay was developed to measure the zones of inhibition against Escherichia coli, Proteus mirabilis, Staphylococcus aureus, and Staphylococcus epidermidis when tubing was immersed in gentamycin, ampicillin, tetracycline, kanamycin, erythromycin, or ciprofloxacin. To further assess the efficacy of this approach, IPP tubing was exposed to ampicillin or ciprofloxacin for 30 seconds, 2 minutes, 10 minutes, or 60 minutes.<br><br>OUTCOMES: Bacterial zones of inhibition against IPP tubing material exposed to various treatments.<br><br>RESULTS: IPP tubing was more effective against Gram-positive bacteria (S aureus and S epidermidis) then Gram-negative bacteria (E coli and P mirabilis). Immersing IPP tubing material in ampicillin or ciprofloxacin increased bactericidal effect of tubing material against Gram-positive and Gram-negative bacteria, respectively. The observed inhibitory effect was time dependent.<br><br>CLINICAL TRANSLATION: Exposing IPP to a specific antimicrobial directly before implantation increases the bactericidal properties of the material, potentially decreasing the likelihood of infection.<br><br>STRENGTHS &amp; LIMITATIONS: This study is limited in that it is in vitro experimentation observing the effect of a single strain of each bacterium. Although the strains used were clinically relevant, further analysis is required to determine whether these results were strain specific.<br><br>CONCLUSION: Immersing IPP material into an antibiotic solution, such as ampicillin or ciprofloxacin, increases the bactericidal properties and may aid in the prevention of infection. Chanyi RM, Alzubaidi R, Leung EJY, Wilcox HB, Brock GB, Burton JP. Inflatable Penile Prostheses Implantation: Does Antibiotic Exposure Matter? Sex Med 2018;6;248-254.}, }
@article {pmid30015225, year = {2018}, author = {Schnorr, SL}, title = {Meanings, measurements, and musings on the significance of patterns in human microbiome variation.}, journal = {Current opinion in genetics &amp; development}, volume = {53}, number = {}, pages = {43-52}, doi = {10.1016/j.gde.2018.06.014}, pmid = {30015225}, issn = {1879-0380}, mesh = {Bacteria/classification/*genetics ; Gastrointestinal Microbiome/*genetics ; Humans ; *Metagenomics ; Microbiota/*genetics ; Transcriptome/genetics ; }, abstract = {Variation of the human microbiome is a multidimensional value depending on the question of interest. Unlike traditional human genetics, which most often deals with variation at the level of genes or genetic sequences, microbiome variation may be most relevant at the functional level and can be interrogated a number of ways. Most common methods are marker gene metataxonomic surveys or shotgun metagenomic sequencing, however more direct indicators of microbial activity that are gaining popularity include metabolomic and metatranscriptomic surveys. With all these data and promise in human microbiome research, it requires that we reassess what is meant by variation of the human microbiome and how its significance impacts the ability of microbiome research to be informative on a range of topics from evolutionary theory to clinical outcomes. Learning from mistakes is essential to advancing the field, and new sophisticated analysis tools are helping to crystallize associations between microbiome variation and its drivers so that firm ground supports future explorations of mechanism. However, the body of current data suggests that these may be highly individualized due to the array of interactions between the host, the microbiome, and the environment. As a result, microbiome researchers need to be cognizant of population contexts and the limits these impose on conclusive outcomes.}, }
@article {pmid30014852, year = {2018}, author = {Yao, L and Seaton, SC and Ndousse-Fetter, S and Adhikari, AA and DiBenedetto, N and Mina, AI and Banks, AS and Bry, L and Devlin, AS}, title = {A selective gut bacterial bile salt hydrolase alters host metabolism.}, journal = {eLife}, volume = {7}, number = {}, pages = {}, pmid = {30014852}, issn = {2050-084X}, support = {P30DK034854/NH/NIH HHS/United States ; U2C DK059637/DK/NIDDK NIH HHS/United States ; P30 DK034854/DK/NIDDK NIH HHS/United States ; P30 DK020593/DK/NIDDK NIH HHS/United States ; P30 CA006516/CA/NCI NIH HHS/United States ; U24 DK059637/DK/NIDDK NIH HHS/United States ; }, mesh = {Amidohydrolases/genetics/*metabolism ; Animals ; Bacteroides thetaiotaomicron/*enzymology/genetics/isolation &amp; purification ; Body Weight ; Circadian Rhythm ; Gastrointestinal Tract/*microbiology ; Gene Expression Profiling ; Germ-Free Life ; *Host Microbial Interactions ; Immunity ; Intestines/physiology ; Liver/physiology ; Metabolism ; Mice ; Respiration ; Taurocholic Acid/*analogs &amp; derivatives/metabolism ; }, abstract = {The human gut microbiota impacts host metabolism and has been implicated in the pathophysiology of obesity and metabolic syndromes. However, defining the roles of specific microbial activities and metabolites on host phenotypes has proven challenging due to the complexity of the microbiome-host ecosystem. Here, we identify strains from the abundant gut bacterial phylum Bacteroidetes that display selective bile salt hydrolase (BSH) activity. Using isogenic strains of wild-type and BSH-deleted Bacteroides thetaiotaomicron, we selectively modulated the levels of the bile acid tauro-β-muricholic acid in monocolonized gnotobiotic mice. B. thetaiotaomicron BSH mutant-colonized mice displayed altered metabolism, including reduced weight gain and respiratory exchange ratios, as well as transcriptional changes in metabolic, circadian rhythm, and immune pathways in the gut and liver. Our results demonstrate that metabolites generated by a single microbial gene and enzymatic activity can profoundly alter host metabolism and gene expression at local and organism-level scales.}, }
@article {pmid30014616, year = {2018}, author = {Rands, CM and Starikova, EV and Brüssow, H and Kriventseva, EV and Govorun, VM and Zdobnov, EM}, title = {ACI-1 beta-lactamase is widespread across human gut microbiomes in Negativicutes due to transposons harboured by tailed prophages.}, journal = {Environmental microbiology}, volume = {20}, number = {6}, pages = {2288-2300}, doi = {10.1111/1462-2920.14276}, pmid = {30014616}, issn = {1462-2920}, support = {IZLRZ3_163863 16-54-21012//Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung/International ; //Russian Foundation for Basic Research/International ; }, abstract = {Antibiotic resistance is increasing among pathogens, and the human microbiome contains a reservoir of antibiotic resistance genes. Acidaminococcus intestini is the first Negativicute bacterium (Gram-negative Firmicute) shown to be resistant to beta-lactam antibiotics. Resistance is conferred by the aci1 gene, but its evolutionary history and prevalence remain obscure. We discovered that ACI-1 proteins are phylogenetically distinct from beta-lactamases of Gram-positive Firmicutes and that aci1 occurs in bacteria scattered across the Negativicute clade, suggesting lateral gene transfer. In the reference A. intestini RyC-MR95 genome, we found transposons residing within a tailed prophage context are likely vehicles for aci1's mobility. We found aci1 in 56 (4.4%) of 1,267 human gut metagenomes, mostly hosted within A. intestini, and, where could be determined, mostly within a consistent mobile element constellation. These samples are from Europe, China and the USA, showing that aci1 is distributed globally. We found that for most Negativicute assemblies with aci1, the prophage observed in A. instestini is absent, but in all cases aci1 is flanked by varying transposons. The chimeric mobile elements we identify here likely have a complex evolutionary history and potentially provide multiple complementary mechanisms for antibiotic resistance gene transfer both within and between cells.}, }
@article {pmid30010322, year = {2018}, author = {Stauber, RH and Siemer, S and Becker, S and Ding, GB and Strieth, S and Knauer, SK}, title = {Small Meets Smaller: Effects of Nanomaterials on Microbial Biology, Pathology, and Ecology.}, journal = {ACS nano}, volume = {12}, number = {7}, pages = {6351-6359}, doi = {10.1021/acsnano.8b03241}, pmid = {30010322}, issn = {1936-086X}, abstract = {As functionalities and levels of complexity in nanomaterials have increased, unprecedented control over microbes has been enabled, as well. In addition to being pathogens and relevant to the human microbiome, microbes are key players for sustainable biotechnology. To overcome current constraints, mechanistic understanding of nanomaterials' physicochemical characteristics and parameters at the nano-bio interface affecting nanomaterial-microbe crosstalk is required. In this Perspective, we describe key nanomaterial parameters and biological outputs that enable controllable microbe-nanomaterial interactions while minimizing design complexity. We discuss the role of biomolecule coronas, including the problem of nanoantibiotic resistance, and speculate on the effects of nanomaterial-microbe complex formation on the outcomes and fates of microbial pathogens. We close by summarizing our current knowledge and noting areas that require further exploration to overcome current limitations for next-generation practical applications of nanotechnology in medicine and agriculture.}, }
@article {pmid30009382, year = {2018}, author = {Ceccarelli, F and Orrù, G and Pilloni, A and Bartosiewicz, I and Perricone, C and Martino, E and Lucchetti, R and Fais, S and Vomero, M and Olivieri, M and di Franco, M and Priori, R and Riccieri, V and Scrivo, R and Shoenfeld, Y and Alessandri, C and Conti, F and Polimeni, A and Valesini, G}, title = {Porphyromonas gingivalis in the tongue biofilm is associated with clinical outcome in rheumatoid arthritis patients.}, journal = {Clinical and experimental immunology}, volume = {194}, number = {2}, pages = {244-252}, pmid = {30009382}, issn = {1365-2249}, mesh = {Adult ; Aged ; Arthritis, Rheumatoid/epidemiology/*immunology ; Bacteroidaceae Infections/epidemiology/*immunology ; Biofilms ; Case-Control Studies ; Cohort Studies ; Disease Progression ; Female ; Humans ; Italy/epidemiology ; Male ; Microbiota/*immunology ; Middle Aged ; Periodontitis/*immunology ; Porphyromonas gingivalis/*physiology ; Prevalence ; Tongue/microbiology/*pathology ; }, abstract = {Several studies have suggested a link between human microbiome and rheumatoid arthritis (RA) development. Porphyromonas gingivalis seems involved in RA initiation and progression, as supported by the high occurrence of periodontitis. In this case-control study, we analysed tongue P. gingivalis presence and quantification in a large healthy and RA cohort. We enrolled 143 RA patients [male/female (M/F) 32/111, mean ± standard deviation (s.d.), age 57·5 ± 19·8 years, mean ± s.d. disease duration 155·9 ± 114·7 months); 36 periodontitis patients (M/F 11/25, mean ± s.d., age 56 ± 9·9 years, mean ± s.d. disease duration 25·5 ± 20·9 months); and 57 patients (M/F 12/45, mean ± s.d., age 61·4 ± 10·9 years, mean ± s.d. disease duration 62·3 ± 66·9 months) with knee osteoarthritis or fibromyalgia. All subjects underwent a standard cytological swab to identify the rate of P. gingivalis/total bacteria by using quantitative real-time polymerase chain reaction. The prevalence of P. gingivalis resulted similarly in RA and periodontitis patients (48·9 versus 52·7%, P = not significant). Moreover, the prevalence of this pathogen was significantly higher in RA and periodontitis patients in comparison with control subjects (P = 0·01 and P = 0·003, respectively). We found a significant correlation between P. gingivalis rate in total bacteria genomes and disease activity score in 28 joints (DAS28) (erythrocyte sedimentation rate) (r = 0·4, P = 0·01). RA patients in remission showed a significantly lower prevalence of P. gingivalis in comparison with non-remission (P = 0·02). We demonstrated a significant association between the percentage of P. gingivalis on the total tongue biofilm and RA disease activity (DAS28), suggesting that the oral cavity microbiological status could play a role in the pathogenic mechanisms of inflammation, leading to more active disease.}, }
@article {pmid30007202, year = {2018}, author = {Stegen, JC and Bottos, EM and Jansson, JK}, title = {A unified conceptual framework for prediction and control of microbiomes.}, journal = {Current opinion in microbiology}, volume = {44}, number = {}, pages = {20-27}, doi = {10.1016/j.mib.2018.06.002}, pmid = {30007202}, issn = {1879-0364}, mesh = {Bacteria/classification/genetics/*growth &amp; development/isolation &amp; purification ; Ecosystem ; Humans ; *Microbiota ; }, abstract = {Microbiomes impact nearly all systems on Earth, and despite vast differences among systems, we contend that it is possible and highly beneficial to develop a unified conceptual framework for understanding microbiome dynamics that is applicable across systems. The ability to robustly predict and control environmental and human microbiomes would provide impactful opportunities to sustain and improve the health of ecosystems and humans alike. Doing so requires understanding the processes governing microbiome temporal dynamics, which currently presents an enormous challenge. We contend, however, that new opportunities can emerge by placing studies of both environmental and human microbiome temporal dynamics in the context of a unified conceptual framework. Our conceptual framework poses that factors influencing the temporal dynamics of microbiomes can be grouped into three broad categories: biotic and abiotic history, internal dynamics, and external forcing factors. Both environmental and human microbiome science study these factors, but not in a coordinated or consistent way. Here we discuss opportunities for greater crosstalk across these domains, such as leveraging specific ecological concepts from environmental microbiome science to guide optimization of strategies to manipulate human microbiomes towards improved health. To achieve unified understanding, it is necessary to have a common body of theory developed from explicit iteration between models and molecular-based characterization of microbiome dynamics across systems. Only through such model-experiment iteration will we eventually achieve prediction and control across microbiomes that impact ecosystem sustainability and human health.}, }
@article {pmid30003599, year = {2019}, author = {Lorimer, J}, title = {Hookworms Make Us Human: The Microbiome, Eco-immunology, and a Probiotic Turn in Western Health Care.}, journal = {Medical anthropology quarterly}, volume = {33}, number = {1}, pages = {60-79}, doi = {10.1111/maq.12466}, pmid = {30003599}, issn = {0745-5194}, mesh = {Ancylostomatoidea ; Animals ; Anthropology, Medical ; *Ecology ; *Hookworm Infections ; Humans ; Infectious Disease Medicine ; *Microbiota ; Probiotics/*therapeutic use ; }, abstract = {Historians of science have identified an ecological turn underway in immunology, driven by the mapping of the human microbiome and wider environmentalist anxieties. A figure is emerging of the human as a holobiont, composed of microbes and threatened by both microbial excess and microbial absence. Antimicrobial approaches to germ warfare are being supplemented by probiotic approaches to restoring microbial life. This article examines the political ecology of this probiotic turn in Western health care. It focuses on Necator americanus-a species of human hookworm-and its relations with immunologists. The analysis moves from a history of human disentanglement from hookworm, to contemporary anxieties about their absence. It examines the reintroduction of worms for helminthic therapy and explores emerging trajectories for probiotic health care involving the synthesis, modification, and/or restoration of worms and their salutary ecologies. The conclusion differentiates these trajectories and identifies an emerging model of &quot;post-paleo&quot; microbiopolitics.}, }
@article {pmid30001289, year = {2018}, author = {Archibugi, L and Signoretti, M and Capurso, G}, title = {The Microbiome and Pancreatic Cancer: An Evidence-based Association?.}, journal = {Journal of clinical gastroenterology}, volume = {52 Suppl 1, Proceedings from the 9th Probiotics, Prebiotics and New Foods, Nutraceuticals and Botanicals for Nutrition &amp; Human and Microbiota Health Meeting, held in Rome, Italy from September 10 to 12, 2017}, number = {}, pages = {S82-S85}, doi = {10.1097/MCG.0000000000001092}, pmid = {30001289}, issn = {1539-2031}, abstract = {Many risk factors for pancreatic cancer are related with microbiome alteration. In the past few years, the human microbiome and its relation with the immune system have been linked with carcinogenesis of different organs distant from the gut, including the pancreas. Patterns of oral microbiome associated with periodontitis are associated with an increased risk of pancreatic cancer, possibly because of the increased systemic inflammatory response, or to the capacity of some specific bacteria to alter the host immune response, making it more favorable to cancer cells. Helicobacter pylori infection when affecting the gastric body mucosa with subsequent hypochlorhydria also seems associated with an increased risk of pancreatic cancer. The composition of the intestinal microbiome is different in animal models and in humans with pancreatic cancer who have a distinct microbiome population compared with controls. Some specific bacteria can migrate from the intestine to the pancreas, and their ablation restores the immune system activity through its reprogramming with a switch toward a Th1 response and displays a protective effect toward tumor growth. More research in this area might lead to progress in terms of pancreatic cancer prevention and treatment, possibly in association with immunotherapy.}, }
@article {pmid29997602, year = {2018}, author = {Xiao, J and Chen, L and Johnson, S and Yu, Y and Zhang, X and Chen, J}, title = {Predictive Modeling of Microbiome Data Using a Phylogeny-Regularized Generalized Linear Mixed Model.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {1391}, pmid = {29997602}, issn = {1664-302X}, abstract = {Recent human microbiome studies have revealed an essential role of the human microbiome in health and disease, opening up the possibility of building microbiome-based predictive models for individualized medicine. One unique characteristic of microbiome data is the existence of a phylogenetic tree that relates all the microbial species. It has frequently been observed that a cluster or clusters of bacteria at varying phylogenetic depths are associated with some clinical or biological outcome due to shared biological function (clustered signal). Moreover, in many cases, we observe a community-level change, where a large number of functionally interdependent species are associated with the outcome (dense signal). We thus develop &quot;glmmTree,&quot; a prediction method based on a generalized linear mixed model framework, for capturing clustered and dense microbiome signals. glmmTree uses the similarity between microbiomes, which is defined based on the microbiome composition and the phylogenetic tree, to predict the outcome. The effects of other predictive variables (e.g., age, sex) can be incorporated readily in the regression framework. Additional tuning parameters enable a data-adaptive approach to capture signals at different phylogenetic depth and abundance level. Simulation studies and real data applications demonstrated that &quot;glmmTree&quot; outperformed existing methods in the dense and clustered signal scenarios.}, }
@article {pmid29988721, year = {2018}, author = {Lourenςo, TGB and Spencer, SJ and Alm, EJ and Colombo, APV}, title = {Defining the gut microbiota in individuals with periodontal diseases: an exploratory study.}, journal = {Journal of oral microbiology}, volume = {10}, number = {1}, pages = {1487741}, pmid = {29988721}, issn = {2000-2297}, abstract = {Background: This exploratory study aimed to characterize the gut microbiome of individuals with different periodontal conditions, and correlate it with periodontal inflammation and tissue destruction. Methods: Stool samples were obtained from individuals presenting periodontal health (PH = 7), gingivitis (G = 14) and chronic periodontitis (CP = 23). The intestinal microbiome composition was determined by Illumina MiSeq sequencing. Results: A lower alpha-diversity in the gut microbiome of individuals with CP was observed, although no significant difference among groups was found (p > 0.01). Firmicutes, Proteobacteria, Verrucomicrobia and Euryarchaeota were increased, whereas Bacteroidetes were decreased in abundance in patients with periodontitis compared to PH. Prevotella (genus), Comamonadaceae (family) and Lactobacillales (order) were detected in higher numbers in G, while Bacteroidales (order) was predominant in PH (p < 0.01). Significant correlations (rho = 0.337-0.468, p < 0.01) were found between OTUs representative of periodontal pathogens and attachment loss. Mogibacteriaceae, Ruminococcaceae and Prevotella were able to discriminate individuals with periodontal diseases from PH (overall accuracy = 84%). Oral taxa were detected in high numbers in all stool samples. Conclusions: Individuals with periodontal diseases present a less diverse gut microbiome consistent with other systemic inflammatory diseases. High numbers of oral taxa related to periodontal destruction and inflammation were detected in the gut microbiome of individuals regardless of periodontal status.}, }
@article {pmid29984938, year = {2018}, author = {Li, BL and Cheng, L and Zhou, XD and Peng, X}, title = {[Research progress on the relationship between oral microbes and digestive system diseases].}, journal = {Hua xi kou qiang yi xue za zhi = Huaxi kouqiang yixue zazhi = West China journal of stomatology}, volume = {36}, number = {3}, pages = {331-335}, doi = {10.7518/hxkq.2018.03.019}, pmid = {29984938}, issn = {2618-0456}, mesh = {*Dental Caries/microbiology ; *Digestive System Diseases/microbiology ; Humans ; *Microbiota ; *Mouth Diseases/microbiology ; *Periodontal Diseases ; }, abstract = {The human microbiome project promoted further understanding on human oral microbes. Besides oral diseases such as dental caries, periodontal disease, and oral cancer, oral microbes are closely associated with systematic diseases. They have a close connection with digestive system diseases and even contribute to the origination and progression of colorectal cancer. By reviewing recent studies involving oral microbe-related digestive systemic diseases, we aim to propose the considerable role of oral microbes in relation to digestive systemic diseases and the way of oral microbes to multiple organs of digestive system.}, }
@article {pmid29983746, year = {2018}, author = {Tipton, L and Cuenco, KT and Huang, L and Greenblatt, RM and Kleerup, E and Sciurba, F and Duncan, SR and Donahoe, MP and Morris, A and Ghedin, E}, title = {Measuring associations between the microbiota and repeated measures of continuous clinical variables using a lasso-penalized generalized linear mixed model.}, journal = {BioData mining}, volume = {11}, number = {}, pages = {12}, pmid = {29983746}, issn = {1756-0381}, support = {K24 HL123342/HL/NHLBI NIH HHS/United States ; U01 AI035042/AI/NIAID NIH HHS/United States ; U01 AI037984/AI/NIAID NIH HHS/United States ; U01 HL098962/HL/NHLBI NIH HHS/United States ; UL1 RR024153/RR/NCRR NIH HHS/United States ; U01 AI031834/AI/NIAID NIH HHS/United States ; U01 AI035004/AI/NIAID NIH HHS/United States ; U01 AI034989/AI/NIAID NIH HHS/United States ; UL1 TR000124/TR/NCATS NIH HHS/United States ; U01 AI037613/AI/NIAID NIH HHS/United States ; M01 RR000722/RR/NCRR NIH HHS/United States ; U01 AI035041/AI/NIAID NIH HHS/United States ; UM1 AI035043/AI/NIAID NIH HHS/United States ; U01 AI034994/AI/NIAID NIH HHS/United States ; K24 HL087713/HL/NHLBI NIH HHS/United States ; UL1 TR000424/TR/NCATS NIH HHS/United States ; R01 HL090339/HL/NHLBI NIH HHS/United States ; U01 AI035043/AI/NIAID NIH HHS/United States ; U01 AI035040/AI/NIAID NIH HHS/United States ; U01 AI034993/AI/NIAID NIH HHS/United States ; UL1 TR000004/TR/NCATS NIH HHS/United States ; U01 AI103408/AI/NIAID NIH HHS/United States ; U01 AI035039/AI/NIAID NIH HHS/United States ; U01 HD032632/HD/NICHD NIH HHS/United States ; U01 AI042590/AI/NIAID NIH HHS/United States ; }, abstract = {Background: Human microbiome studies in clinical settings generally focus on distinguishing the microbiota in health from that in disease at a specific point in time. However, microbiome samples may be associated with disease severity or continuous clinical health indicators that are often assessed at multiple time points. While the temporal data from clinical and microbiome samples may be informative, analysis of this type of data can be problematic for standard statistical methods.<br><br>Results: To identify associations between microbiota and continuous clinical variables measured repeatedly in two studies of the respiratory tract, we adapted a statistical method, the lasso-penalized generalized linear mixed model (LassoGLMM). LassoGLMM can screen for associated clinical variables, incorporate repeated measures of individuals, and address the large number of species found in the microbiome. As is common in microbiome studies, when the number of variables is an order of magnitude larger than the number of samples LassoGLMM can be imperfect in its variable selection. We overcome this limitation by adding a pre-screening step to reduce the number of variables evaluated in the model. We assessed the use of this adapted two-stage LassoGLMM for its ability to determine which microbes are associated with continuous repeated clinical measures.We found associations (retaining a non-zero coefficient in the LassoGLMM) between 10 laboratory measurements and 43 bacterial genera in the oral microbiota, and between 2 cytokines and 3 bacterial genera in the lung. We compared our associations with those identified by the Wilcoxon test after dichotomizing our outcomes and identified a non-significant trend towards differential abundance between high and low outcomes. Our two-step LassoGLMM explained more of the variance seen in the outcome of interest than other variants of the LassoGLMM method.<br><br>Conclusions: We demonstrated a method that can account for the large number of genera detected in microbiome studies and repeated measures of clinical or longitudinal studies, allowing for the detection of strong associations between microbes and clinical measures. By incorporating the design strengths of repeated measurements and a prescreening step to aid variable selection, our two-step LassoGLMM will be a useful analytic method for investigating relationships between microbes and repeatedly measured continuous outcomes.}, }
@article {pmid29976412, year = {2018}, author = {George Kerry, R and Patra, JK and Gouda, S and Park, Y and Shin, HS and Das, G}, title = {Benefaction of probiotics for human health: A review.}, journal = {Journal of food and drug analysis}, volume = {26}, number = {3}, pages = {927-939}, doi = {10.1016/j.jfda.2018.01.002}, pmid = {29976412}, issn = {1021-9498}, abstract = {Humans are a unique reservoir of heterogeneous and vivacious group of microbes, which together forms the human-microbiome superorganism. Human gut serves as a home to over 100-1000 microbial species, which primarily modulate the host internal environment and thereby, play a major role in host health. This spectacular symbiotic relationship has attracted extensive research in this field. More specifically, these organisms play key roles in defense function, eupepsia along with catabolism and anabolism, and impact brain-gut responses. The emergence of microbiota with resistance and tolerance to existing conventional drugs and antibiotics has decreased the drug efficacies. Furthermore, the modern biotechnology mediated nano-encapsulated multiplex supplements appear to be high cost and inconvenient. Henceforth, a simple, low-cost, receptive and intrinsic approach to achieve health benefits is vital in the present era. Supplementation with probiotics, prebiotics, and synbiotics has shown promising results against various enteric pathogens due to their unique ability to compete with pathogenic microbiota for adhesion sites, to alienate pathogens or to stimulate, modulate and regulate the host's immune response by initiating the activation of specific genes in and outside the host intestinal tract. Probiotics have also been shown to regulate fat storage and stimulate intestinal angiogenesis. Hence, this study aims to underline the possible beneficial impact of probiotics for human health and medical sectors and for better lifestyle.}, }
@article {pmid29974051, year = {2018}, author = {Fankhauser, M and Moser, C and Nyfeler, T}, title = {Patents as Early Indicators of Technology and Investment Trends: Analyzing the Microbiome Space as a Case Study.}, journal = {Frontiers in bioengineering and biotechnology}, volume = {6}, number = {}, pages = {84}, pmid = {29974051}, issn = {2296-4185}, abstract = {The human microbiome is the collective of microbes living in symbiosis on and within humans. Modulating its composition and function has become an attractive means for the prevention and treatment of a variety of diseases including cancer. Since the initiation of the human microbiome project in 2007, the number of academic publications and active patent families around the microbiome has grown exponentially. Screening patent databases can be useful for the early detection and the tracking of new technology trends. However, it is not sufficient to assess portfolio sizes because emerging players with small but high-quality patent portfolios will be missed within the noise of large but low-quality portfolio owners. Here we used the consolidated database and software tool PatentSight to benchmark patent portfolios, and to analyze key patent owners and innovators in the microbiome space. Our study shows how in-depth patent analyses combining qualitative and quantitative parameters can identify actionable early indicators of technology and investment trends from large patent datasets.}, }
@article {pmid29973493, year = {2018}, author = {Castilla, IA and Woods, DF and Reen, FJ and O'Gara, F}, title = {Harnessing Marine Biocatalytic Reservoirs for Green Chemistry Applications through Metagenomic Technologies.}, journal = {Marine drugs}, volume = {16}, number = {7}, pages = {}, pmid = {29973493}, issn = {1660-3397}, mesh = {Animals ; Aquatic Organisms/*metabolism ; Biocatalysis ; Esterases/metabolism ; Humans ; Lipase/metabolism ; Metagenomics/methods ; }, abstract = {In a demanding commercial world, large-scale chemical processes have been widely utilised to satisfy consumer related needs. Chemical industries are key to promoting economic growth and meeting the requirements of a sustainable industrialised society. The market need for diverse commodities produced by the chemical industry is rapidly expanding globally. Accompanying this demand is an increased threat to the environment and to human health, due to waste produced by increased industrial production. This increased demand has underscored the necessity to increase reaction efficiencies, in order to reduce costs and increase profits. The discovery of novel biocatalysts is a key method aimed at combating these difficulties. Metagenomic technology, as a tool for uncovering novel biocatalysts, has great potential and applicability and has already delivered many successful achievements. In this review we discuss, recent developments and achievements in the field of biocatalysis. We highlight how green chemistry principles through the application of biocatalysis, can be successfully promoted and implemented in various industrial sectors. In addition, we demonstrate how two novel lipases/esterases were mined from the marine environment by metagenomic analysis. Collectively these improvements can result in increased efficiency, decreased energy consumption, reduced waste and cost savings for the chemical industry.}, }
@article {pmid29963639, year = {2018}, author = {Nieves-Ramírez, ME and Partida-Rodríguez, O and Laforest-Lapointe, I and Reynolds, LA and Brown, EM and Valdez-Salazar, A and Morán-Silva, P and Rojas-Velázquez, L and Morien, E and Parfrey, LW and Jin, M and Walter, J and Torres, J and Arrieta, MC and Ximénez-García, C and Finlay, BB}, title = {Asymptomatic Intestinal Colonization with Protist Blastocystis Is Strongly Associated with Distinct Microbiome Ecological Patterns.}, journal = {mSystems}, volume = {3}, number = {3}, pages = {}, pmid = {29963639}, issn = {2379-5077}, abstract = {Blastocystis is the most prevalent protist of the human intestine, colonizing approximately 20% of the North American population and up to 100% in some nonindustrialized settings. Blastocystis is associated with gastrointestinal and systemic disease but can also be an asymptomatic colonizer in large populations. While recent findings in humans have shown bacterial microbiota changes associated with this protist, it is unknown whether these occur due to the presence of Blastocystis or as a result of inflammation. To explore this, we evaluated the fecal bacterial and eukaryotic microbiota in 156 asymptomatic adult subjects from a rural population in Xoxocotla, Mexico. Colonization with Blastocystis was strongly associated with an increase in bacterial alpha diversity and broad changes in beta diversity and with more discrete changes to the microbial eukaryome. More than 230 operational taxonomic units (OTUs), including those of dominant species Prevotella copri and Ruminococcus bromii, were differentially abundant in Blastocystis-colonized individuals. Large functional changes accompanied these observations, with differential abundances of 202 (out of 266) predicted metabolic pathways (PICRUSt), as well as lower fecal concentrations of acetate, butyrate, and propionate in colonized individuals. Fecal calprotectin was markedly decreased in association with Blastocystis colonization, suggesting that this ecological shift induces subclinical immune consequences to the asymptomatic host. This work is the first to show a direct association between the presence of Blastocystis and shifts in the gut bacterial and eukaryotic microbiome in the absence of gastrointestinal disease or inflammation. These results prompt further investigation of the role Blastocystis and other eukaryotes play within the human microbiome. IMPORTANCE Given the results of our study and other reports of the effects of the most common human gut protist on the diversity and composition of the bacterial microbiome, Blastocystis and, possibly, other gut protists should be studied as ecosystem engineers that drive community diversity and composition.}, }
@article {pmid29963028, year = {2018}, author = {Petrova, MI and Macklaim, JM and Wuyts, S and Verhoeven, T and Vanderleyden, J and Gloor, GB and Lebeer, S and Reid, G}, title = {Comparative Genomic and Phenotypic Analysis of the Vaginal Probiotic Lactobacillus rhamnosus GR-1.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {1278}, pmid = {29963028}, issn = {1664-302X}, abstract = {Lactobacillus represents a versatile bacterial genus, which can adapt to a wide variety of ecological niches, including human body sites such as the intestinal and urogenital tract. In this study, the complete genome sequence of the vaginal probiotic Lactobacillus rhamnosus GR-1 was determined and compared to other L. rhamnosus strains at genomic and phenotypic level. The strain GR-1 was originally isolated from a female urethra, and was assessed with L. rhamnosus GG from a feces sample of a healthy male, and L. rhamnosus LC705 from a dairy product. A key difference is the absence in GR-1 and LC705 of the spaCBA locus required for pili-mediated intestinal epithelial adhesion. In addition, the L. rhamnosus GR-1 genome contains a unique cluster for exopolysaccharide production, which is postulated to synthesize glucose-rich, rhamnose-lacking exopolysaccharide molecules that are different from the galactose-rich extracellular polysaccharide of L. rhamnosus GG. Compared to L. rhamnosus GG, L. rhamnosus GR-1 was also genetically predicted and experimentally shown to better metabolize lactose and maltose, and to better withstand oxidative stress, which is of relevance in the vagina. This study could thus provide a molecular framework for the selection of the optimal probiotic strain for each targeted niche and condition, but further substantiation of niche adaptation mechanisms of lactobacilli is warranted.}, }
@article {pmid29962006, year = {2018}, author = {Jakobsen, TH and Eickhardt, SR and Gheorghe, AG and Stenqvist, C and Sønderholm, M and Stavnsberg, C and Jensen, PØ and Odgaard, A and Whiteley, M and Moser, C and Hvolris, J and Hougen, HP and Bjarnsholt, T}, title = {Implants induce a new niche for microbiomes.}, journal = {APMIS : acta pathologica, microbiologica, et immunologica Scandinavica}, volume = {126}, number = {8}, pages = {685-692}, doi = {10.1111/apm.12862}, pmid = {29962006}, issn = {1600-0463}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Bacteria/classification/*isolation &amp; purification ; Bacterial Typing Techniques ; Bone Regeneration/physiology ; Case-Control Studies ; Female ; Foreign Bodies/*microbiology ; Fractures, Bone/microbiology/surgery ; Fungi/classification/*isolation &amp; purification ; Humans ; Male ; Middle Aged ; Mycological Typing Techniques ; Prostheses and Implants/*microbiology ; Prosthesis Failure ; Prosthesis-Related Infections/*microbiology ; }, abstract = {Although much work is being done to develop new treatments, research and knowledge regarding factors underlying implant-related microbial colonization leading to infection are less comprehensive. Presence of microorganisms in and around implants clinically characterized as uninfected remains unknown. The objective of this study was to detect and identify bacteria and fungi on implants from various groups of patients with no prior indications of implant related infections. Patient samples (implants and tissue) were collected from five different hospitals in the Capital region of Denmark. By in-depth microbiological detection methods, we examined the prevalence of bacteria and fungi on 106 clinically uninfected implants from four patient groups (aseptic loosening, healed fractures, craniofacial complications and recently deceased). Of 106 clinically uninfected implants and 39 negative controls investigated, 66% were colonized by bacteria and 40% were colonized by fungi (p < 0.0001 compared to negative controls). A large number of microbes were found to colonize the implants, however, the most prevalent microbes present were not common aetiological agents of implant infections. The findings indicate that implants provide a distinct niche for microbial colonization. These data have broad implications for medical implant recipients, as well as for supporting the idea that the presence of foreign objects in the body alters the human microbiome by providing new colonization niches.}, }
@article {pmid29960810, year = {2019}, author = {Primec, M and Klemenak, M and Di Gioia, D and Aloisio, I and Bozzi Cionci, N and Quagliariello, A and Gorenjak, M and Mičetić-Turk, D and Langerholc, T}, title = {Clinical intervention using Bifidobacterium strains in celiac disease children reveals novel microbial modulators of TNF-α and short-chain fatty acids.}, journal = {Clinical nutrition (Edinburgh, Scotland)}, volume = {38}, number = {3}, pages = {1373-1381}, doi = {10.1016/j.clnu.2018.06.931}, pmid = {29960810}, issn = {1532-1983}, abstract = {BACKGROUND &amp; AIMS: Celiac disease (CD) is an immune-mediated systemic disease, caused by ingestion of gluten in genetically predisposed individuals. Gut microbiota dysbiosis might play a significant role in pathogenesis of chronic enteropathies and its modulation can be used as an intervention strategy in CD as well. In this study, we aimed to identify correlations between fecal microbiota, serum tumor necrosis factor alpha (TNF-α) and fecal short-chain fatty acids (SCFAs) in healthy children and children with CD after administration of probiotic Bifidobacterium breve BR03 and B632.<br><br>METHODS: A double-blind placebo-controlled study enrolled 40 children with CD (CD) and 16 healthy children (HC). CD children were randomly allocated into two groups, of which 20 belonged to the placebo (PL) group and 20 to the Probiotic (PR) group. The PR group received a probiotic formulation containing a mixture of 2 strains, B. breve BR03 (DSM 16604) and B. breve B632 (DSM 24706) in 1:1 ratio for 3 months. Subsequently, for statistical analysis, blood and fecal samples from CD children (on enrolment - T0 and after 3 months, at the end of intervention with probiotic/placebo - T1) and HC children were used. The HC group was sampled only once (T0).<br><br>RESULTS: Verrucomicrobia, Parcubacteria and some yet unknown phyla of Bacteria and Archaea may be involved in the disease, indicated by a strong correlation to TNF-α. Likewise, Proteobacteria strongly correlated with fecal SCFAs concentration. The effect of probiotic administration has disclosed a negative correlation between Verrucomicrobia, some unknown phyla of Bacteria, Synergistetes, Euryarchaeota and some SCFAs, turning them into an important target in microbiome restoration process. Synergistetes and Euryarchaeota may have a role in the anti-inflammatory process in healthy human gut.<br><br>CONCLUSIONS: Our results highlight new phyla, which may have an important relation to disease-related parameters, CD itself and health.}, }
@article {pmid29951378, year = {2018}, author = {Scapaticci, M and Bartolini, A and Del Chierico, F and Accardi, C and Di Girolamo, F and Masotti, A and Muraca, M and Putignani, L}, title = {Phenotypic typing and epidemiological survey of antifungal resistance of Candida species detected in clinical samples of Italian patients in a 17 months' period.}, journal = {Germs}, volume = {8}, number = {2}, pages = {58-66}, pmid = {29951378}, issn = {2248-2997}, abstract = {Introduction: Yeast pathogens are emerging agents of nosocomial as well as community-acquired infections and their rapid and accurate identification is crucial for a better management of high-risk patients and for an adequate treatment.<br><br>Methods: We performed a retrospective review of 156 yeast isolates collected during a 17 months' period of regular clinical practice at the Microbiology Department of San Camillo Hospital in Treviso, Italy and analyzed by the traditional culture-based method combined with matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS).<br><br>Results: Out of all the samples collected MALDI-TOF MS was able to characterize with a MT score ≥1.7 (accurate result at species level) 12 different yeast and yeast-like species from 140 samples: Candida albicans (63.7%), Candida glabrata (13.6%), Saccharomyces cerevisiae (6.5%), Candida parapsilosis (5.7%), Candida tropicalis (2.1%), Candida pararugosa (2.1%), Candida guilliermondii (2.1%), Candida kefyr (1.4%), Candida lusitaniae (0.7%), Candida palmioleophila (0.7%), Geotrichum silvicola (0.7%), Rhodotorula mucilaginosa (0.7%). Susceptibility testing toward seven common antifungal agents showed a characteristic MIC distribution of C. albicans isolates for echinocandins: particularly we noticed that 72% and 46% of C. albicans showed an MIC value close to clinical breakpoint as defined by EUCAST, respectively for anidulafungin and micafungin.<br><br>Conclusion: Accurate identification of microorganisms and the study of their antifungal susceptibility allow to understand the epidemiology of a particular area, permitting the choice of the most appropriate early antifungal treatment.}, }
@article {pmid29951086, year = {2018}, author = {Hadrich, D}, title = {Microbiome Research Is Becoming the Key to Better Understanding Health and Nutrition.}, journal = {Frontiers in genetics}, volume = {9}, number = {}, pages = {212}, pmid = {29951086}, issn = {1664-8021}, abstract = {The human microbiome has emerged as the crucial moderator in the interactions between food and our body. It is increasingly recognised that the microbiome can change our mind and health status, or switch on a wide range of diseases including cancer, cardio-metabolic diseases, allergies, and obesity. The causes of diseases are often only partially understood. However, nutrients, metabolites, and microbes are increasingly regarded as key players, even where the complete disease mechanisms remain unclear. The key to progress in the future will be to use and exploit additional, newly emerging disciplines such as metagenomics to complement patient information and to bring our understanding of diseases and the interrelation and effects of nutritional molecules to the next level. The EU has already funded 216 projects under the 7th Framework Programme and Horizon 2020 programmes to promote metagenomics and to advance our knowledge of microbes. This support started with the catalysing MetaHIT project that has produced a catalogue of gut microbes, and has arrived now at the very multi-disciplinary SYSCID action looking at how the microbiome is driving its resilience potential and our health. Together, these projects involve an investment of more than €498 M. However, in Horizon 2020, the new EU Health and Food Work Programmes for 2018-2020 go even further by setting new goals to find applications and to generate more knowledge on the microbiome, nutrition, various hosts of microbes, and their relation to health and disease. The big vision is to modulate health and diseases via the microbiome and nutrition, while at the same time other factors such as omics, molecular signatures, and lifestyle are constant. In this way, microbiome and nutrition research is moving from an isolated and despised offside position to a beacon of hope with a lot of potential and possibilities.}, }
@article {pmid29943448, year = {2018}, author = {Marchesi, JR}, title = {Advancing microbiome research.}, journal = {Immunology}, volume = {}, number = {}, pages = {}, pmid = {29943448}, issn = {1365-2567}, }
@article {pmid29942682, year = {2018}, author = {Paul, C and Bayrychenko, Z and Junier, T and Filippidou, S and Beck, K and Bueche, M and Greub, G and Bürgmann, H and Junier, P}, title = {Dissemination of antibiotic resistance genes associated with the sporobiota in sediments impacted by wastewater.}, journal = {PeerJ}, volume = {6}, number = {}, pages = {e4989}, pmid = {29942682}, issn = {2167-8359}, abstract = {Aquatic ecosystems serve as a dissemination pathway and a reservoir of both antibiotic resistant bacteria (ARB) and antibiotic resistance genes (ARG). In this study, we investigate the role of the bacterial sporobiota to act as a vector for ARG dispersal in aquatic ecosystems. The sporobiota was operationally defined as the resilient fraction of the bacterial community withstanding a harsh extraction treatment eliminating the easily lysed fraction of the total bacterial community. The sporobiota has been identified as a critical component of the human microbiome, and therefore potentially a key element in the dissemination of ARG in human-impacted environments. A region of Lake Geneva in which the accumulation of ARG in the sediments has been previously linked to the deposition of treated wastewater was selected to investigate the dissemination of tet(W) and sul1, two genes conferring resistance to tetracycline and sulfonamide, respectively. Analysis of the abundance of these ARG within the sporobiome (collection of genes of the sporobiota) and correlation with community composition and environmental parameters demonstrated that ARG can spread across the environment with the sporobiota being the dispersal vector. A highly abundant OTU affiliated with the genus Clostridium was identified as a potential specific vector for the dissemination of tet(W), due to a strong correlation with tet(W) frequency (ARG copy numbers/ng DNA). The high dispersal rate, long-term survival, and potential reactivation of the sporobiota constitute a serious concern in terms of dissemination and persistence of ARG in the environment.}, }
@article {pmid29941067, year = {2018}, author = {Marchesi, JR}, title = {Advancing microbiome research.}, journal = {Microbiology (Reading, England)}, volume = {164}, number = {8}, pages = {1005-1006}, doi = {10.1099/mic.0.000688}, pmid = {29941067}, issn = {1465-2080}, mesh = {Biomedical Research/*methods ; High-Throughput Nucleotide Sequencing ; Humans ; Microbiota/*physiology ; }, }
@article {pmid29937405, year = {2018}, author = {Chang, CY and Yan, X and Crnovcic, I and Annaval, T and Chang, C and Nocek, B and Rudolf, JD and Yang, D and Hindra,  and Babnigg, G and Joachimiak, A and Phillips, GN and Shen, B}, title = {Resistance to Enediyne Antitumor Antibiotics by Sequestration.}, journal = {Cell chemical biology}, volume = {25}, number = {9}, pages = {1075-1085.e4}, pmid = {29937405}, issn = {2451-9448}, support = {R01 GM115575/GM/NIGMS NIH HHS/United States ; U01 GM098248/GM/NIGMS NIH HHS/United States ; R01 CA204484/CA/NCI NIH HHS/United States ; R01 CA078747/CA/NCI NIH HHS/United States ; U54 GM094585/GM/NIGMS NIH HHS/United States ; R01 GM109456/GM/NIGMS NIH HHS/United States ; }, mesh = {Anthraquinones/*chemistry/metabolism/*pharmacology ; Antibiotics, Antineoplastic/*chemistry/metabolism/*pharmacology ; Drug Resistance, Bacterial ; Enediynes/*chemistry/metabolism/*pharmacology ; Genes, Bacterial ; Humans ; Models, Molecular ; Multigene Family ; Streptomyces/drug effects/*genetics/metabolism ; }, abstract = {The enediynes, microbial natural products with extraordinary cytotoxicities, have been translated into clinical drugs. Two self-resistance mechanisms are known in the enediyne producers-apoproteins for the nine-membered enediynes and self-sacrifice proteins for the ten-membered enediyne calicheamicin. Here we show that: (1) tnmS1, tnmS2, and tnmS3 encode tiancimycin (TNM) resistance in its producer Streptomyces sp. CB03234, (2) tnmS1, tnmS2, and tnmS3 homologs are found in all anthraquinone-fused enediyne producers, (3) TnmS1, TnmS2, and TnmS3 share a similar β barrel-like structure, bind TNMs with nanomolar KD values, and confer resistance by sequestration, and (4) TnmS1, TnmS2, and TnmS3 homologs are widespread in nature, including in the human microbiome. These findings unveil an unprecedented resistance mechanism for the enediynes. Mechanisms of self-resistance in producers serve as models to predict and combat future drug resistance in clinical settings. Enediyne-based chemotherapies should now consider the fact that the human microbiome harbors genes encoding enediyne resistance.}, }
@article {pmid29931340, year = {2018}, author = {van Dijkhuizen, EHP and Aidonopoulos, O and Ter Haar, NM and Pires Marafon, D and Magni-Manzoni, S and Ioannidis, YE and Putignani, L and Vastert, SJ and Malattia, C and De Benedetti, F and Martini, A}, title = {Prediction of inactive disease in juvenile idiopathic arthritis: a multicentre observational cohort study.}, journal = {Rheumatology (Oxford, England)}, volume = {57}, number = {10}, pages = {1752-1760}, doi = {10.1093/rheumatology/key148}, pmid = {29931340}, issn = {1462-0332}, mesh = {*Algorithms ; Arthritis, Juvenile/*pathology ; Child ; Child, Preschool ; Female ; Humans ; Male ; Predictive Value of Tests ; Prognosis ; Prospective Studies ; *Severity of Illness Index ; }, abstract = {Objectives: To predict the occurrence of inactive disease in JIA in the first 2 years of disease.<br><br>Methods: An inception cohort of 152 treatment-naïve JIA patients with disease duration <6 months was analysed. Potential predictors were baseline clinical variables, joint US, gut microbiota composition and a panel of inflammation-related compounds in blood plasma. Various algorithms were employed to predict inactive disease according to Wallace criteria at 6-month intervals in the first 2 years. Performance of the models was evaluated using the split-cohort technique. The cohort was analysed in its entirety, and separate models were developed for oligoarticular patients, polyarticular RF negative patients and ANA positive patients.<br><br>Results: All models analysing the cohort as a whole showed poor performance in test data [area under the curve (AUC): <0.65]. The subgroup models performed better. Inactive disease was predicted by lower baseline juvenile arthritis DAS (JADAS)-71 and lower relative abundance of the operational taxonomic unit Mogibacteriaceae for oligoarticular patients (AUC in test data: 0.69); shorter duration of morning stiffness, higher haemoglobin and lower CXCL-9 levels at baseline for polyarticular RF negative patients (AUC in test data: 0.69); and shorter duration of morning stiffness and higher baseline haemoglobin for ANA positive patients (AUC in test data: 0.72).<br><br>Conclusion: Inactive disease could not be predicted with satisfactory accuracy in the whole cohort, likely due to disease heterogeneity. Interesting predictors were found in more homogeneous subgroups. These need to be validated in future studies.}, }
@article {pmid29927545, year = {2018}, author = {Bäumel, S and Tytgat, HLP and Nemec, B and Schmidt, R and Chia, LW and Smidt, H}, title = {Fifty Percent Human - how art brings us in touch with our microbial cohabitants.}, journal = {Microbial biotechnology}, volume = {11}, number = {4}, pages = {571-574}, pmid = {29927545}, issn = {1751-7915}, mesh = {*Art ; Creativity ; Ecosystem ; Humans ; *Microbiota ; Philosophy ; }, abstract = {The Human Microbiome, as well as the exploration of the microorganisms inhabiting the human body, are not only integral to the field of microbiology but represent an intrinsic part of all human beings. Consequently, along with scientists, artists have been inspired by the microbiome: transforming it in to tangible artefacts in order to critically question, reflect on and break down the barrier between humans and their microcohabitants. By artistic means, artists help us to understand how microbial research topics are inevitably affected by societal influences, including (health) politics, economics and the arts. Fifty Percent Human is a multidisciplinary artistic research project that aims to reshape our understanding of the human body and its environment as well as to explore possibilities for conscious coexistence in order to bridge the gap between science and society.}, }
@article {pmid29922272, year = {2018}, author = {Del Chierico, F and Abbatini, F and Russo, A and Quagliariello, A and Reddel, S and Capoccia, D and Caccamo, R and Ginanni Corradini, S and Nobili, V and De Peppo, F and Dallapiccola, B and Leonetti, F and Silecchia, G and Putignani, L}, title = {Gut Microbiota Markers in Obese Adolescent and Adult Patients: Age-Dependent Differential Patterns.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {1210}, pmid = {29922272}, issn = {1664-302X}, abstract = {Obesity levels, especially in children, have dramatically increased over the last few decades. Recently, several studies highlighted the involvement of gut microbiota in the pathophysiology of obesity. We investigated the composition of gut microbiota in obese adolescents and adults compared to age-matched normal weight (NW) volunteers in order to assemble age- and obesity-related microbiota profiles. The composition of gut microbiota was analyzed by 16S rRNA-based metagenomics. Ecological representations of microbial communities were computed, and univariate, multivariate, and correlation analyses performed on bacterial profiles. The prediction of metagenome functional content from 16S rRNA gene surveys was carried out. Ecological analyses revealed a dissimilarity among the subgroups, and resultant microbiota profiles differed between obese adolescents and adults. Using statistical analyses, we assigned, as microbial markers, Faecalibacterium prausnitzii and Actinomyces to the microbiota of obese adolescents, and Parabacteroides, Rikenellaceae, Bacteroides caccae, Barnesiellaceae, and Oscillospira to the microbiota of NW adolescents. The predicted metabolic profiles resulted different in adolescent groups. Particularly, biosynthesis of primary bile acid and steroid acids, metabolism of fructose, mannose, galactose, butanoate, and pentose phosphate and glycolysis/gluconeogenesis were for the majority associated to obese, while biosynthesis and metabolism of glycan, biosynthesis of secondary bile acid, metabolism of steroid hormone and lipoic acid were associated to NW adolescents. Our study revealed unique features of gut microbiota in terms of ecological patterns, microbial composition and metabolism in obese patients. The assignment of novel obesity bacterial markers may open avenues for the development of patient-tailored treatments dependent on age-related microbiota profiles.}, }
@article {pmid29917039, year = {2019}, author = {Noguera-Julian, M and González-Beiras, C and Parera, M and Ubals, M and Kapa, A and Paredes, R and Mitjà, O}, title = {Etiological Characterization of the Cutaneous Ulcer Syndrome in Papua New Guinea Using Shotgun Metagenomics.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {68}, number = {3}, pages = {482-489}, doi = {10.1093/cid/ciy502}, pmid = {29917039}, issn = {1537-6591}, abstract = {Background: Treponema pallidum subsp pertenue and Haemophilus ducreyi are causative agents of cutaneous ulcer (CU) in yaws-endemic regions in the tropics. However, a significant proportion of CU patients remain polymerase chain reaction (PCR) negative for both bacterial agents. We aimed to identify potential additional etiological agents of CU in a yaws-endemic region.<br><br>Methods: This population-based cohort study included children in Lihir Island (Papua New Guinea) examined during a yaws eradication campaign in October 2013-October 2014. All consenting patients with atraumatic exudative ulcers of >1 cm diameter were enrolled. Lesional swabs were collected for real-time PCR testing for T. pallidum subsp pertenue and H. ducreyi. We then performed shotgun whole DNA metagenomics sequencing on extracted DNA and taxonomically assigned shotgun sequences using a human microbiome reference.<br><br>Results: Sequence data were available for 122 samples. Shotgun sequencing showed high classification agreement relative to PCR testing (area under the curve for T. pallidum/H. ducreyi was 0.92/0.85, respectively). Clustering analysis of shotgun data revealed compositional clusters where the dominant species (median relative abundance ranged from 32% to 66%) was H. ducreyi (23% of specimens), T. pallidum subsp pertenue (16%), Streptococcus dysgalactiae (12%), Arcanobacterium haemolyticum (8%), and Corynebacterium diphtheriae (8%). Sample clustering derived from ulcer microbial composition did not show geographical patterns.<br><br>Conclusions: These data suggest a diverse etiology of skin ulcers in yaws-endemic areas, which may help design more accurate diagnostic tools and more effective antimicrobial treatment approaches to the cutaneous ulcer syndrome.}, }
@article {pmid29915115, year = {2018}, author = {Shen, M and Yang, Y and Shen, W and Cen, L and McLean, JS and Shi, W and Le, S and He, X}, title = {A Linear Plasmid-Like Prophage of Actinomyces odontolyticus Promotes Biofilm Assembly.}, journal = {Applied and environmental microbiology}, volume = {84}, number = {17}, pages = {}, pmid = {29915115}, issn = {1098-5336}, support = {R01 DE020102/DE/NIDCR NIH HHS/United States ; R01 DE023810/DE/NIDCR NIH HHS/United States ; R01 DE026186/DE/NIDCR NIH HHS/United States ; }, abstract = {The human oral cavity is home to a large number of bacteria and bacteriophages (phages). However, the biology of oral phages as members of the human microbiome is not well understood. Recently, we isolated Actinomyces odontolyticus subsp. actinosynbacter strain XH001 from the human oral cavity, and genomic analysis revealed the presence of an intact prophage named xhp1. Here, we demonstrated that xhp1 is a linear plasmid-like prophage, which is a newly identified phage of A. odontolyticus The prophage xhp1 genome is a 35-kb linear double-stranded DNA with 10-bp single-stranded, 3' cohesive ends. xhp1 exists extrachromosomally, with an estimated copy number of 5. Annotation of xhp1 revealed 54 open reading frames, while phylogenetic analysis suggests that it has limited similarity with other phages. xhp1 phage particles can be induced by mitomycin C and belong to the Siphoviridae family, according to transmission electron microscopic examination. The released xhp1 particles can reinfect the xhp1-cured XH001 strain and result in tiny blurry plaques. Moreover, xhp1 promotes XH001 biofilm formation through spontaneous induction and the release of host extracellular DNA (eDNA). In conclusion, we identified a linear plasmid-like prophage of A. odontolyticus, which enhances bacterial host biofilm assembly and could be beneficial to the host for its persistence in the oral cavity.IMPORTANCE The biology of phages as members of the human oral microbiome is understudied. Here, we report the characterization of xhp1, a novel linear plasmid-like prophage identified from a human oral isolate, Actinomyces odontolyticus subsp. actinosynbacter strain XH001. xhp1 can be induced and reinfect xhp1-cured XH001. The spontaneous induction of xhp1 leads to the lysis of a subpopulation of bacterial hosts and the release of eDNA that promotes biofilm assembly, thus potentially contributing to the persistence of A. odontolyticus within the oral cavity.}, }
@article {pmid29913479, year = {2018}, author = {Ismail, T and Fatima, N and Muhammad, SA and Zaidi, SS and Rehman, N and Hussain, I and Tariq, NUS and Amirzada, I and Mannan, A}, title = {Prioritizing and modelling of putative drug target proteins of Candida albicans by systems biology approach.}, journal = {Acta biochimica Polonica}, volume = {65}, number = {2}, pages = {209-218}, doi = {10.18388/abp.2017_2327}, pmid = {29913479}, issn = {1734-154X}, mesh = {Antifungal Agents/pharmacology ; Candida albicans/*chemistry/drug effects ; Fungal Proteins/analysis/*genetics ; Humans ; Models, Molecular ; Molecular Docking Simulation ; Subcellular Fractions/chemistry ; Systems Biology/*methods ; }, abstract = {Candida albicans (Candida albicans) is one of the major sources of nosocomial infections in humans which may prove fatal in 30% of cases. The hospital acquired infection is very difficult to treat affectively due to the presence of drug resistant pathogenic strains, therefore there is a need to find alternative drug targets to cure this infection. In silico and computational level frame work was used to prioritize and establish antifungal drug targets of Candida albicans. The identification of putative drug targets was based on acquiring 5090 completely annotated genes of Candida albicans from available databases which were categorized into essential and non-essential genes. The result indicated that 9% of proteins were essential and could become potential candidates for intervention which might result in pathogen eradication. We studied cluster of orthologs and the subtractive genomic analysis of these essential proteins against human genome was made as a reference to minimize the side effects. It was seen that 14% of Candida albicans proteins were evolutionary related to the human proteins while 86% are non-human homologs. In the next step of compatible drug target selections, the non-human homologs were sequentially compared to the human microbiome data to minimize the potential effects against gut flora which accumulated to 38% of the essential genome. The sub-cellular localization of these candidate proteins in fungal cellular systems indicated that 80% of them are cytoplasmic, 10% are mitochondrial and the remaining 10% are associated with the cell wall. The role of these non-human and non-gut flora putative target proteins in Candida albicans biological pathways was studied. Due to their integrated and critical role in Candida albicans replication cycle, four proteins were selected for molecular modeling. For drug designing and development, four high quality and reliable protein models with more than 70% sequence identity were constructed. These proteins are used for the docking studies of the known and new ligands (unpublished data). Our study will be an effective framework for drug target identifications of pathogenic microbial strains and development of new therapies against the infections they cause.}, }
@article {pmid29913309, year = {2018}, author = {Schirmer, M and Kumar, V and Netea, MG and Xavier, RJ}, title = {The causes and consequences of variation in human cytokine production in health.}, journal = {Current opinion in immunology}, volume = {54}, number = {}, pages = {50-58}, doi = {10.1016/j.coi.2018.05.012}, pmid = {29913309}, issn = {1879-0372}, mesh = {B-Lymphocytes/immunology ; Cytokines/*biosynthesis/*immunology ; *Health ; Humans ; Immune System Diseases/immunology ; T-Lymphocytes, Regulatory/immunology ; }, abstract = {Cytokines are important cell-signaling molecules that activate and modulate immune responses. Major factors influencing cytokine variation in healthy individuals are host genetics, non-heritable factors and the microbiome. Genetic variation accounts for a significant part of heterogeneity in cytokine production by peripheral blood mononuclear cells. Variation in cytokines such as IL-6 and IL-6Ra is strongly influenced by heritability, suggesting an evolutionarily pressure for their genetic regulation that potentially contributes to differences in immune responsiveness between human populations. Non-heritable factors, including age, body weight and environmental variables such as seasonality, drive variation in baseline cytokine levels. Age further affects pathogen-induced lymphocyte-derived cytokine responses, whereas seasonality affects monocyte-derived cytokine production in response to influenza virus, Coxiella burnetti or Cryptococcus neoformans. Another influential factor that shapes the immune system is the human microbiome. Microbes and microbial products (e.g. short-chain fatty acids and tryptophan metabolites) possess strong immunomodulatory effects, induce regulatory T cells and lead to the diversification of B cells and the production of specific antibodies. In particular, differential TNFα and IFNγ production is associated with the gut microbiome. Understanding causes of variation in the healthy human immune system can reveal factors that lead to aberrant cytokine production in immune-related disorders.}, }
@article {pmid29912913, year = {2018}, author = {McMillan, A and Rulisa, S and Gloor, GB and Macklaim, JM and Sumarah, M and Reid, G}, title = {Pilot assessment of probiotics for pregnant women in Rwanda.}, journal = {PloS one}, volume = {13}, number = {6}, pages = {e0195081}, pmid = {29912913}, issn = {1932-6203}, support = {227328//Canadian Institute Health Research/International ; }, mesh = {Adolescent ; Adult ; Female ; Humans ; *Lactobacillus rhamnosus ; *Microbiota ; Middle Aged ; Pilot Projects ; Pregnancy ; Probiotics/*administration &amp; dosage ; Rwanda ; Vagina/*microbiology ; }, abstract = {BACKGROUND: While the global market for probiotics is soon to reach in excess of US$50 billion, the continent of Africa has been largely ignored, despite these products having the ability to reduce the burden of disease and death.<br><br>TRIAL DESIGN: The present randomised, blinded, placebo-controlled clinical trial was undertaken in Rwanda, a country devoid of well-documented probiotics. The primary outcome aim was to examine receptivity and compliance for orally administered probiotic capsules containing Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 in pregnant women and assess any initial side effects or changes to the vaginal microbiome.<br><br>METHODS: Pregnant women between the ages of 18 and 55 were recruited from the Nyamata District Hospital in Rwanda and randomly assigned to receive probiotic or placebo capsules for one month. Clinicians were blinded to the treatments.<br><br>RESULTS: The drop-out rate was 21%, with 13 of 18 women in the placebo group and 17 of 20 in the probiotic group completing the study. Only 13 women returned for birthing and additional sample collection. No side effects of either treatment group were reported. Microbiota and metabolomics data showed similar findings to those reported in the literature, with low bacterial diversity and Lactobacillus dominance associated with a healthy vagina, and birthing associated with high diversity. Despite the small sample size and lack of changes in the microbiota, women in the placebo arm were significantly more likely to give birth pre-term.<br><br>CONCLUSION: Overall women were receptive to the probiotic concept, but the lack of information on such products and logistical and economical challenges pose problems for wider population engagement.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov NCT02150655.}, }
@article {pmid29910789, year = {2018}, author = {Pannaraj, PS and Ly, M and Cerini, C and Saavedra, M and Aldrovandi, GM and Saboory, AA and Johnson, KM and Pride, DT}, title = {Shared and Distinct Features of Human Milk and Infant Stool Viromes.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {1162}, pmid = {29910789}, issn = {1664-302X}, support = {K23 HD072774/HD/NICHD NIH HHS/United States ; }, abstract = {Infants acquire many of their microbes from their mothers during the birth process. The acquisition of these microbes is believed to be critical in the development of the infant immune system. Bacteria also are transmitted to the infant through breastfeeding, and help to form the microbiome of the infant gastrointestinal (GI) tract; it is unknown whether viruses in human milk serve to establish an infant GI virome. We examined the virome contents of milk and infant stool in a cohort of mother-infant pairs to discern whether milk viruses colonize the infant GI tract. We observed greater viral alpha diversity in milk than in infant stool, similar to the trend we found for bacterial communities from both sites. When comparing beta diversity, viral communities were mostly distinguishable between milk and infant stool, but each was quite distinct from adult stool, urine, and salivary viromes. There were significant differences in viral families in the infant stool (abundant bacteriophages from the family Siphoviridae) compared to milk (abundant bacteriophages from the family Myoviridae), which may reflect significant differences in the bacterial families identified from both sites. Despite the differences in viral taxonomy, we identified a significant number of shared viruses in the milk and stool from all mother-infant pairs. Because of the significant proportion of bacteriophages transmitted in these mother-infant pairs, we believe the transmission of milk phages to the infant GI tract may help to shape the infant GI microbiome.}, }
@article {pmid29908759, year = {2018}, author = {Qiu, B and Al, K and Pena-Diaz, AM and Athwal, GS and Drosdowech, D and Faber, KJ and Burton, JP and O'Gorman, DB}, title = {Cutibacterium acnes and the shoulder microbiome.}, journal = {Journal of shoulder and elbow surgery}, volume = {27}, number = {10}, pages = {1734-1739}, doi = {10.1016/j.jse.2018.04.019}, pmid = {29908759}, issn = {1532-6500}, mesh = {Acinetobacter/*isolation &amp; purification ; Adolescent ; Adult ; Aged ; Cartilage, Articular/microbiology ; DNA, Bacterial/*analysis ; Gram-Positive Bacterial Infections/microbiology ; Humans ; Ligaments, Articular/microbiology ; Microbiota ; Middle Aged ; Propionibacterium acnes/*isolation &amp; purification ; RNA, Ribosomal, 16S/*analysis ; Rotator Cuff/microbiology ; Shoulder/*microbiology ; Shoulder Joint/surgery ; Skin/microbiology ; Subcutaneous Fat/microbiology ; Young Adult ; }, abstract = {BACKGROUND: Advances in DNA sequencing technologies have made it possible to detect microbial genome sequences (microbiomes) within tissues once thought to be sterile. We used this approach to gain insights into the likely sources of Cutibacterium acnes (formerly Propionibacterium acnes) infections within the shoulder.<br><br>METHODS: Tissue samples were collected from the skin, subcutaneous fat, anterior supraspinatus tendon, middle glenohumeral ligament, and humeral head cartilage of 23 patients (14 male and 9 female patients) during primary arthroplasty surgery. Total DNA was extracted and microbial 16S ribosomal RNA sequencing was performed using an Illumina MiSeq system. Data analysis software was used to generate operational taxonomic units for quantitative and statistical analyses.<br><br>RESULTS: After stringent removal of contamination, genomic DNA from various Acinetobacter species and from the Oxalobacteraceae family was identified in 74% of rotator cuff tendon tissue samples. C acnes DNA was detected in the skin of 1 male patient but not in any other shoulder tissues.<br><br>CONCLUSION: Our findings indicate the presence of a low-abundance microbiome in the rotator cuff and, potentially, in other shoulder tissues. The absence of C acnes DNA in all shoulder tissues assessed other than the skin is consistent with the hypothesis that C acnes infections are derived from skin contamination during surgery and not from opportunistic expansion of a resident C acnes population in the shoulder joint.}, }
@article {pmid29908580, year = {2018}, author = {Ely, PH}, title = {Is psoriasis a bowel disease? Successful treatment with bile acids and bioflavonoids suggests it is.}, journal = {Clinics in dermatology}, volume = {36}, number = {3}, pages = {376-389}, doi = {10.1016/j.clindermatol.2018.03.011}, pmid = {29908580}, issn = {1879-1131}, mesh = {Animals ; Anti-Bacterial Agents/therapeutic use ; Bacterial Translocation ; Bile Acids and Salts/*therapeutic use ; Biological Variation, Individual ; Diet ; Endotoxemia/complications/drug therapy ; Endotoxins/*metabolism ; Flavonoids/*therapeutic use ; *Gastrointestinal Microbiome ; Gastrointestinal Tract/immunology ; Helicobacter Infections/complications/drug therapy ; Helicobacter pylori ; Humans ; Peptidoglycan/*metabolism ; Psoriasis/*drug therapy/*microbiology ; }, abstract = {The gut is the largest lymphoid organ in the body. The human microbiome is composed of trillions of bacteria. The DNA of these bacteria dwarfs the human genome. Diet and ethanol can cause rapid shifts in the number and types of bacteria in the gut. The psoriatic microbiome is similar to that seen in alcoholics; there is a decrease in bacterial diversity and overgrowth of bacteria in the small bowel. Psoriatics often have liver disease and deficiencies in bile acids. Psoriasis is a disease characterized by a leaky gut. All of the comorbidities of this disease are due to systemic endotoxemia. Bacterial peptidoglycans absorbed from the gut have direct toxic effects on the liver and skin. Their absorption, as well as endotoxin absorption, must be eliminated to treat psoriasis successfully. Endotoxin absorption is markedly increased by ethanol and peppers. Bioflavonoids, such as quercetin and citrus bioflavonoids, prevent this absorption. Bile acids, given orally, break up endotoxin in the intestinal lumen. Pathogens, including Helicobacter pylori and Streptococcus pyogenes, must be eliminated with antimicrobial therapy for any treatment to work. A complete protocol for curing psoriasis is provided.}, }
@article {pmid29902438, year = {2018}, author = {Milshteyn, A and Colosimo, DA and Brady, SF}, title = {Accessing Bioactive Natural Products from the Human Microbiome.}, journal = {Cell host &amp; microbe}, volume = {23}, number = {6}, pages = {725-736}, doi = {10.1016/j.chom.2018.05.013}, pmid = {29902438}, issn = {1934-6069}, support = {R01 AT009562/AT/NCCIH NIH HHS/United States ; }, mesh = {Anti-Bacterial Agents/metabolism ; Bacteria/genetics/metabolism ; Biological Products/*metabolism/*pharmacology ; Humans ; Indoles/metabolism ; Metabolomics ; Metagenomics ; Microbial Interactions ; Microbiota/genetics/*physiology ; Multigene Family ; Peptides, Cyclic/metabolism ; Pyrrolidonecarboxylic Acid/metabolism ; Thiazolidines/metabolism ; }, abstract = {Natural products have long played a pivotal role in the development of therapeutics for a variety of diseases. Traditionally, soil and marine environments have provided a rich reservoir from which diverse chemical scaffolds could be discovered. Recently, the human microbiome has been recognized as a promising niche from which secondary metabolites with therapeutic potential have begun to be isolated. In this Review, we address how the expansive history of identifying bacterial natural products in other environments is informing the approaches being brought to bear on the study of the human microbiota. We also touch on how these tools can lead to insights about microbe-microbe and host-microbe interactions and help generate biological hypotheses that may lead to developments of new therapeutic modalities.}, }
@article {pmid29900563, year = {2018}, author = {Coleman, M and Elkins, C and Gutting, B and Mongodin, E and Solano-Aguilar, G and Walls, I}, title = {Microbiota and Dose Response: Evolving Paradigm of Health Triangle.}, journal = {Risk analysis : an official publication of the Society for Risk Analysis}, volume = {38}, number = {10}, pages = {2013-2028}, doi = {10.1111/risa.13121}, pmid = {29900563}, issn = {1539-6924}, mesh = {Animals ; *Bacteria ; *Dysbiosis ; *Gastrointestinal Microbiome ; Genomics ; Humans ; Immunity, Innate ; Immunity, Mucosal ; Intestines/immunology/microbiology ; Mice ; Models, Biological ; Prebiotics ; Probiotics/*analysis ; Risk Assessment/*methods ; }, abstract = {SRA Dose-Response and Microbial Risk Analysis Specialty Groups jointly sponsored symposia that addressed the intersections between the &quot;microbiome revolution&quot; and dose response. Invited speakers presented on innovations and advances in gut and nasal microbiota (normal microbial communities) in the first decade after the Human Microbiome Project began. The microbiota and their metabolites are now known to influence health and disease directly and indirectly, through modulation of innate and adaptive immune systems and barrier function. Disruption of healthy microbiota is often associated with changes in abundance and diversity of core microbial species (dysbiosis), caused by stressors including antibiotics, chemotherapy, and disease. Nucleic-acid-based metagenomic methods demonstrated that the dysbiotic host microbiota no longer provide normal colonization resistance to pathogens, a critical component of innate immunity of the superorganism. Diverse pathogens, probiotics, and prebiotics were considered in human and animal models (in vivo and in vitro). Discussion included approaches for design of future microbial dose-response studies to account for the presence of the indigenous microbiota that provide normal colonization resistance, and the absence of the protective microbiota in dysbiosis. As NextGen risk analysis methodology advances with the &quot;microbiome revolution,&quot; a proposed new framework, the Health Triangle, may replace the old paradigm based on the Disease Triangle (focused on host, pathogen, and environment) and germophobia. Collaborative experimental designs are needed for testing hypotheses about causality in dose-response relationships for pathogens present in our environments that clearly compete in complex ecosystems with thousands of bacterial species dominating the healthy superorganism.}, }
@article {pmid29899737, year = {2018}, author = {Xun, Z and Zhang, Q and Xu, T and Chen, N and Chen, F}, title = {Dysbiosis and Ecotypes of the Salivary Microbiome Associated With Inflammatory Bowel Diseases and the Assistance in Diagnosis of Diseases Using Oral Bacterial Profiles.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {1136}, pmid = {29899737}, issn = {1664-302X}, abstract = {Inflammatory bowel diseases (IBDs) are chronic, idiopathic, relapsing disorders of unclear etiology affecting millions of people worldwide. Aberrant interactions between the human microbiota and immune system in genetically susceptible populations underlie IBD pathogenesis. Despite extensive studies examining the involvement of the gut microbiota in IBD using culture-independent techniques, information is lacking regarding other human microbiome components relevant to IBD. Since accumulated knowledge has underscored the role of the oral microbiota in various systemic diseases, we hypothesized that dissonant oral microbial structure, composition, and function, and different community ecotypes are associated with IBD; and we explored potentially available oral indicators for predicting diseases. We examined the 16S rRNA V3-V4 region of salivary bacterial DNA from 54 ulcerative colitis (UC), 13 Crohn's disease (CD), and 25 healthy individuals using Illumina sequencing. Distinctive sample clusters were driven by disease or health based on principal coordinate analysis (PCoA) of both the Operational Taxonomic Unit profile and Kyoto Encyclopedia of Genes and Genomes pathways. Comparisons of taxa abundances revealed enrichment of Streptococcaceae (Streptococcus) and Enterobacteriaceae in UC and Veillonellaceae (Veillonella) in CD, accompanied by depletion of Lachnospiraceae and [Prevotella] in UC and Neisseriaceae (Neisseria) and Haemophilus in CD, most of which have been demonstrated to exhibit the same variation tendencies in the gut of IBD patients. IBD-related oral microorganisms were associated with white blood cells, reduced basic metabolic processes, and increased biosynthesis and transport of substances facilitating oxidative stress and virulence. Furthermore, UC and CD communities showed robust sub-ecotypes that were not demographic or severity-specific, suggesting their value for future applications in precision medicine. Additionally, indicator species analysis revealed several genera indicative of UC and CD, which were confirmed in a longitudinal cohort. Collectively, this study demonstrates evident salivary dysbiosis and different ecotypes in IBD communities and provides an option for identifying at-risk populations, not only enhancing our understanding of the IBD microbiome apart from the gut but also offering a clinically useful strategy to track IBD as saliva can be sampled conveniently and non-invasively.}, }
@article {pmid29898981, year = {2018}, author = {Bansal, S and Nguyen, JP and Leligdowicz, A and Zhang, Y and Kain, KC and Ricciuto, DR and Coburn, B}, title = {Rectal and Naris Swabs: Practical and Informative Samples for Analyzing the Microbiota of Critically Ill Patients.}, journal = {mSphere}, volume = {3}, number = {3}, pages = {}, pmid = {29898981}, issn = {2379-5042}, support = {FDN-14839//CIHR/Canada ; }, mesh = {Cluster Analysis ; *Critical Illness ; DNA, Ribosomal/chemistry/genetics ; Feces/microbiology ; Humans ; Intensive Care Units ; *Microbiota ; Nose/*microbiology ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Rectum/*microbiology ; Sequence Analysis, DNA ; Skin/microbiology ; }, abstract = {Commensal microbiota are immunomodulatory, and their pathological perturbation can affect the risk and outcomes of infectious and inflammatory diseases. Consequently, the human microbiota is an emerging diagnostic and therapeutic target in critical illness. In this study, we compared four sample types-rectal, naris, and antecubital swabs and stool samples-for 16S rRNA gene microbiota sequencing in intensive care unit (ICU) patients. Stool samples were obtained in only 31% of daily attempts, while swabs were reliably obtained (≥97% of attempts). Swabs were compositionally distinct by anatomical site, and rectal swabs identified within-patient temporal trends in microbiota composition. Rectal swabs from ICU patients demonstrated differences from healthy stool similar to those observed in comparing stool samples from ICU patients to those from the same healthy controls. Rectal swabs are a useful complement to other sample types for analysis of the intestinal microbiota in critical illness, particularly when obtaining stool may not be feasible or practical.IMPORTANCE Perturbation of the microbiome has been correlated with various infectious and inflammatory diseases and is common in critically ill patients. Stool is typically used to sample the microbiota in human observational studies; however, it is often unavailable for collection from critically ill patients, reducing its utility as a sample type to study this population. Our research identified alternatives to stool for sampling the microbiota during critical illness. Rectal and naris swabs were practical alternatives for use in these patients, as they were observed to be more reliably obtained than stool, were suitable for culture-independent analysis, and successfully captured within- and between-patient microbiota differences.}, }
@article {pmid29896176, year = {2018}, author = {Elbehery, AHA and Feichtmayer, J and Singh, D and Griebler, C and Deng, L}, title = {The Human Virome Protein Cluster Database (HVPC): A Human Viral Metagenomic Database for Diversity and Function Annotation.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {1110}, pmid = {29896176}, issn = {1664-302X}, abstract = {Human virome, including those of bacteria (bacteriophages) have received an increasing attention recently, owing to the rapid developments in human microbiome research and the awareness of the far-reaching influence of microbiomes on health and disease. Nevertheless, human viromes are still underrepresented in literature making viruses a virtually untapped resource of diversity, functional and physiological information. Here we present the human virome protein cluster database as an effort to improve functional annotation and characterization of human viromes. The database was built out of hundreds of virome datasets from six different body sites. We also show the utility of this database through its use for the characterization of three bronchoalveolar lavage (BAL) viromes from one healthy control in addition to one moderate and one severe chronic obstructive pulmonary disease (COPD) patients. The use of the database allowed for a better functional annotation, which were otherwise poorly characterized when limited to annotation using sequences from full-length viral genomes. In addition, our BAL samples gave a first insight into viral communities of COPD patients and confirm a state of dysbiosis for viruses that increases with disease progression. Moreover, they shed light on the potential role of phages in the horizontal gene transfer of bacterial virulence factors, a phenomenon that highlights a possible contribution of phages to etiopathology.}, }
@article {pmid29895255, year = {2019}, author = {Katsi, V and Didagelos, M and Skevofilax, S and Armenis, I and Kartalis, A and Vlachopoulos, C and Karvounis, H and Tousoulis, D}, title = {GUT Microbiome-GUT Dysbiosis-Arterial Hypertension: New Horizons.}, journal = {Current hypertension reviews}, volume = {15}, number = {1}, pages = {40-46}, doi = {10.2174/1573402114666180613080439}, pmid = {29895255}, issn = {1875-6506}, mesh = {Animals ; Antihypertensive Agents/therapeutic use ; *Arterial Pressure/drug effects ; Bacteria/drug effects/*growth &amp; development ; Disease Models, Animal ; Dysbiosis ; *Gastrointestinal Microbiome/drug effects ; Host-Pathogen Interactions ; Humans ; Hypertension/drug therapy/epidemiology/*microbiology/*physiopathology ; Intestines/*microbiology ; Probiotics/therapeutic use ; Risk Factors ; }, abstract = {Arterial hypertension is a progressive cardiovascular syndrome arising from complex and interrelated etiologies. The human microbiome refers to the community of microorganisms that live in or on the human body. They influence human physiology by interfering in several processes such as providing nutrients and vitamins in Phase I and Phase II drug metabolism. The human gut microbiota is represented mainly by Firmicutes and Bacteroidetes and to a lesser degree by Actinobacteria and Proteobacteria, with each individual harbouring at least 160 such species. Gut microbiota contributes to blood pressure homeostasis and the pathogenesis of arterial hypertension through production, modification, and degradation of a variety of microbial-derived bioactive metabolites. Animal studies and to a lesser degree human research has unmasked relative mechanisms, mainly through the effect of certain microbiome metabolites and their receptors, outlining this relationship. Interventions to utilize these pathways, with probiotics, prebiotics, antibiotics and fecal microbiome transplantation have shown promising results. Personalized microbiome-based disease prediction and treatment responsiveness seem futuristic. Undoubtedly, a long way of experimental and clinical research should be pursued to elucidate this novel, intriguing and very promising horizon.}, }
@article {pmid29881381, year = {2018}, author = {Tsigalou, C and Stavropoulou, E and Bezirtzoglou, E}, title = {Current Insights in Microbiome Shifts in Sjogren's Syndrome and Possible Therapeutic Interventions.}, journal = {Frontiers in immunology}, volume = {9}, number = {}, pages = {1106}, pmid = {29881381}, issn = {1664-3224}, mesh = {Clinical Decision-Making ; Combined Modality Therapy ; Diet Therapy ; Disease Management ; Humans ; Microbiota/*immunology ; Probiotics ; Sjogren's Syndrome/etiology/metabolism/*therapy ; Treatment Outcome ; }, abstract = {Sjogren's syndrome (SS) is an autoimmune disease, among the most common ones, that targets mainly the exocrine glands as well as extra-glandular epithelial tissues. Their lymphocytic infiltration leads to manifestations from other organs (e.g., kidneys, lungs, liver, or thyroid), apart from sicca symptoms (xerostomia and keratoconjunctivitis). SS is more prevalent in women than in men (9:1). Moreover, p.SS patients are in increased risk to develop lymphoma. Certain autoantibodies (e.g., antibodies against ribonucleoprotein autoantigens Ro-SSA and La-SSB) are ultimate hallmarks for the disease. It was not known until recently that culture-independent techniques like next-generation sequencing (NGS) facilitate the study of the microbe communities in humans and scientists achieved to define the outlines of the microbiome contribution in health and disease. Researchers have started to investigate the alterations in diversity of the oral, ocular, or intestinal microbiota in SS. Recent studies indicate that dysbiosis may play a significant role in SS pathogenesis. At the same time, the cause or effect is not clear yet because the dysfunction of salivary glands induces alterations in oral and intestinal microbiome which is linked to worsen of symptoms and disease severity. If the human microbiome proves to play a key role in pathogenesis and manifestation of SS, the next step could be new and promising therapeutic approaches such as probiotics or prebiotics. This mini review focuses on the alterations of microbiome of SS patients, their connection with immune tolerance and new therapeutic strategies involving diet manipulation toward future personalized medicine.}, }
@article {pmid29878050, year = {2018}, author = {Albayrak, L and Khanipov, K and Golovko, G and Fofanov, Y}, title = {Detection of multi-dimensional co-exclusion patterns in microbial communities.}, journal = {Bioinformatics (Oxford, England)}, volume = {34}, number = {21}, pages = {3695-3701}, doi = {10.1093/bioinformatics/bty414}, pmid = {29878050}, issn = {1367-4811}, abstract = {Motivation: Identification of complex relationships among members of microbial communities is key to understand and control the microbiota. Co-exclusion is arguably one of the most important patterns reflecting micro-organisms' intolerance to each other's presence. Knowing these relations opens an opportunity to manipulate microbiotas, personalize anti-microbial and probiotic treatments as well as guide microbiota transplantation. The co-exclusion pattern however, cannot be appropriately described by a linear function nor its strength be estimated using covariance or (negative) Pearson and Spearman correlation coefficients. This manuscript proposes a way to quantify the strength and evaluate the statistical significance of co-exclusion patterns between two, three or more variables describing a microbiota and allows one to extend analysis beyond micro-organism abundance by including other microbiome associated measurements such as, pH, temperature etc., as well as estimate the expected numbers of false positive co-exclusion patterns in a co-exclusion network.<br><br>Results: The implemented computational pipeline (CoEx) tested against 2380 microbial profiles (samples) from The Human Microbiome Project resulted in body-site specific pairwise co-exclusion patterns.<br><br>C++ source code for calculation of the score and P-value for two, three and four dimensional co-exclusion patterns as well as source code and executable files for the CoEx pipeline are available at https://scsb.utmb.edu/labgroups/fofanov/co-exclusion_in_microbial_communities.asp.<br><br>Supplementary information: Supplementary data are available at Bioinformatics online.}, }
@article {pmid29875143, year = {2018}, author = {Wandro, S and Osborne, S and Enriquez, C and Bixby, C and Arrieta, A and Whiteson, K}, title = {The Microbiome and Metabolome of Preterm Infant Stool Are Personalized and Not Driven by Health Outcomes, Including Necrotizing Enterocolitis and Late-Onset Sepsis.}, journal = {mSphere}, volume = {3}, number = {3}, pages = {}, pmid = {29875143}, issn = {2379-5042}, support = {U24 DK097154/DK/NIDDK NIH HHS/United States ; }, mesh = {Cluster Analysis ; DNA, Bacterial/chemistry/genetics ; DNA, Ribosomal/chemistry/genetics ; Enterocolitis, Necrotizing/*microbiology ; Feces/*chemistry/*microbiology ; Gas Chromatography-Mass Spectrometry ; *Gastrointestinal Microbiome ; Humans ; Infant ; Infant, Newborn ; *Infant, Premature ; Infant, Very Low Birth Weight ; Late Onset Disorders ; *Metabolome ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sepsis/*microbiology ; Sequence Analysis, DNA ; }, abstract = {The assembly and development of the gut microbiome in infants have important consequences for immediate and long-term health. Preterm infants represent an abnormal case for bacterial colonization because of early exposure to bacteria and frequent use of antibiotics. To better understand the assembly of the gut microbiota in preterm infants, fecal samples were collected from 32 very low birth weight preterm infants over the first 6 weeks of life. Infant health outcomes included health, late-onset sepsis, and necrotizing enterocolitis (NEC). We characterized bacterial compositions by 16S rRNA gene sequencing and metabolomes by untargeted gas chromatography-mass spectrometry. Preterm infant fecal samples lacked beneficial Bifidobacterium spp. and were dominated by Enterobacteriaceae, Enterococcus, and Staphylococcus organisms due to nearly uniform antibiotic administration. Most of the variance between the microbial community compositions could be attributed to the baby from which the sample derived (permutational multivariate analysis of variance [PERMANOVA] R2 = 0.48, P < 0.001), while clinical status (health, NEC, or late-onset sepsis) and overlapping times in the neonatal intensive care unit (NICU) did not explain a significant amount of variation in bacterial composition. Fecal metabolomes were also found to be unique to the individual (PERMANOVA R2 = 0.43, P < 0.001) and weakly associated with bacterial composition (Mantel statistic r = 0.23 ± 0.05, P < 0.05). No measured metabolites were found to be associated with necrotizing enterocolitis, late-onset sepsis, or a healthy outcome. Overall, preterm infant gut microbial communities were personalized and reflected antibiotic usage.IMPORTANCE Preterm infants face health problems likely related to microbial exposures, including sepsis and necrotizing enterocolitis. However, the role of the gut microbiome in preterm infant health is poorly understood. Microbial colonization differs from that of healthy term babies because it occurs in the NICU and is often perturbed by antibiotics. We measured bacterial compositions and metabolomic profiles of 77 fecal samples from 32 preterm infants to investigate the differences between microbiomes in health and disease. Rather than finding microbial signatures of disease, we found that both the preterm infant microbiome and the metabolome were personalized and that the preterm infant gut microbiome is enriched in microbes that commonly dominate in the presence of antibiotics. These results contribute to the growing knowledge of the preterm infant microbiome and emphasize that a personalized view will be important to disentangle the health consequences of the preterm infant microbiome.}, }
@article {pmid29870114, year = {2018}, author = {Chin-Yee, B and Subramanian, SV and Verma, AA and Laupacis, A and Razak, F}, title = {Emerging Trends in Clinical Research: With Implications for Population Health and Health Policy.}, journal = {The Milbank quarterly}, volume = {96}, number = {2}, pages = {369-401}, pmid = {29870114}, issn = {1468-0009}, mesh = {Clinical Nursing Research/*trends ; Clinical Trials as Topic/*statistics &amp; numerical data ; Forecasting ; Health Equity/*trends ; Health Policy/*trends ; Humans ; Population Health/*statistics &amp; numerical data ; }, abstract = {Policy Points: Significant advances in clinical medicine that have broader societal relevance may be less accessible to population health researchers and policymakers because of increased specialization within fields. We describe important recent clinical advances and discuss their broader societal impact. These advances include more expansive strategies for disease prevention, the rise of precision medicine, applications of human microbiome research, and new and highly successful treatments for hepatitis C infection. These recent developments in clinical research raise important issues surrounding health care costs and equitable resource allocation that necessitate an ongoing dialogue among the fields of clinical medicine, population health, and health policy.<br><br>CONTEXT: Developments in clinical medicine have important implications for population health, and there is a need for interdisciplinary engagement among clinical medicine, the social sciences, and public health research. The aim of this article is to help bridge the divide between these fields by exploring major recent advances in clinical medicine that have important implications for population health.<br><br>METHODS: We reviewed the most cited articles published from 2010 to 2015 in 5 high-impact clinical journals and selected 5 randomized controlled trials and 2 related clinical practice guidelines that are broadly relevant to population health and policy.<br><br>FINDINGS: We discuss the following themes: (1) expanding indications for drug therapy and the inherent medicalization of the population as highlighted by studies and clinical guidelines supporting lower blood pressure targets or widespread statin use; (2) the tension in nutritional research between quantifying the impact of isolated nutrients and studying specific foods and dietary patterns, for example, the role of the Mediterranean diet in the primary prevention of cardiovascular disease; (3) the issue of high medication costs and the challenge of providing equitable access raised by the development of new and effective treatments for hepatitis C infection; (4) emerging clinical applications of research on the human microbiome as illustrated by fecal transplant to treat Clostridium difficile infections; and (5) the promise and limitations of precision medicine as demonstrated by the rise of novel targeted therapies in oncology.<br><br>CONCLUSIONS: These developments in clinical science hold promise for improving individual and population health and raise important questions about resource allocation, the role of prevention, and health disparities.}, }
@article {pmid29868846, year = {2018}, author = {Sankaran, K and Holmes, SP}, title = {Latent variable modeling for the microbiome.}, journal = {Biostatistics (Oxford, England)}, volume = {}, number = {}, pages = {}, doi = {10.1093/biostatistics/kxy018}, pmid = {29868846}, issn = {1468-4357}, support = {R01 AI112401/AI/NIAID NIH HHS/United States ; }, abstract = {The human microbiome is a complex ecological system, and describing its structure and function under different environmental conditions is important from both basic scientific and medical perspectives. Viewed through a biostatistical lens, many microbiome analysis goals can be formulated as latent variable modeling problems. However, although probabilistic latent variable models are a cornerstone of modern unsupervised learning, they are rarely applied in the context of microbiome data analysis, in spite of the evolutionary, temporal, and count structure that could be directly incorporated through such models. We explore the application of probabilistic latent variable models to microbiome data, with a focus on Latent Dirichlet allocation, Non-negative matrix factorization, and Dynamic Unigram models. To develop guidelines for when different methods are appropriate, we perform a simulation study. We further illustrate and compare these techniques using the data of Dethlefsen and Relman (2011, Incomplete recovery and individualized responses of the human distal gut microbiota to repeated antibiotic perturbation. Proceedings of the National Academy of Sciences108, 4554-4561), a study on the effects of antibiotics on bacterial community composition. Code and data for all simulations and case studies are available publicly.}, }
@article {pmid29868514, year = {2018}, author = {Chai, Q and Zhang, Y and Liu, CH}, title = {Mycobacterium tuberculosis: An Adaptable Pathogen Associated With Multiple Human Diseases.}, journal = {Frontiers in cellular and infection microbiology}, volume = {8}, number = {}, pages = {158}, pmid = {29868514}, issn = {2235-2988}, mesh = {Autoimmune Diseases/complications ; Granuloma/immunology ; Host-Pathogen Interactions/*immunology ; Humans ; *Immune System ; Metabolic Syndrome/complications ; Microbial Interactions/immunology ; Microbiota ; Mycobacterium tuberculosis/*pathogenicity ; Recurrence ; Tuberculosis/complications/*immunology/microbiology ; Tuberculosis, Pulmonary/complications ; }, abstract = {Mycobacterium tuberculosis, the etiological agent of tuberculosis (TB), is an extremely successful pathogen that adapts to survive within the host. During the latency phase of infection, M. tuberculosis employs a range of effector proteins to be cloud the host immune system and shapes its lifestyle to reside in granulomas, sophisticated, and organized structures of immune cells that are established by the host in response to persistent infection. While normally being restrained in immunocompetent hosts, M. tuberculosis within granulomas can cause the recrudescence of TB when host immunity is compromised. Aside from causing TB, accumulating evidence suggests that M. tuberculosis is also associated with multiple other human diseases, such as pulmonary complications, autoimmune diseases, and metabolic syndromes. Furthermore, it has been recently appreciated that M. tuberculosis infection can also reciprocally interact with the human microbiome, which has a strong link to immune balance and health. In this review, we highlight the adaptive survival of M. tuberculosis within the host and provide an overview for regulatory mechanisms underlying interactions between M. tuberculosis infection and multiple important human diseases. A better understanding of how M. tuberculosis regulates the host immune system to cause TB and reciprocally regulates other human diseases is critical for developing rational treatments to better control TB and help alleviate its associated comorbidities.}, }
@article {pmid29844606, year = {2018}, author = {Reid, G}, title = {What are bacteria doing in the bladder?.}, journal = {Nature reviews. Urology}, volume = {15}, number = {8}, pages = {469-470}, doi = {10.1038/s41585-018-0032-y}, pmid = {29844606}, issn = {1759-4820}, mesh = {Bacteria ; Female ; Humans ; *Microbiota ; *Urinary Bladder ; Urogenital System ; }, }
@article {pmid29802603, year = {2018}, author = {Stefano, GB and Pilonis, N and Ptacek, R and Raboch, J and Vnukova, M and Kream, RM}, title = {Gut, Microbiome, and Brain Regulatory Axis: Relevance to Neurodegenerative and Psychiatric Disorders.}, journal = {Cellular and molecular neurobiology}, volume = {38}, number = {6}, pages = {1197-1206}, pmid = {29802603}, issn = {1573-6830}, mesh = {Animals ; Brain/*metabolism/physiopathology ; Dysbiosis/*genetics ; Gastrointestinal Microbiome/*genetics ; Humans ; Mental Disorders/genetics/physiopathology ; Microbiota/*genetics ; Parkinson Disease/*genetics/physiopathology ; }, abstract = {It has become apparent that the molecular and biochemical integrity of interactive families, genera, and species of human gut microflora is critically linked to maintaining complex metabolic and behavioral processes mediated by peripheral organ systems and central nervous system neuronal groupings. Relatively recent studies have established intrinsic ratios of enterotypes contained within the human microbiome across demographic subpopulations and have empirically linked significant alterations in the expression of bacterial enterotypes with the initiation and persistence of several major metabolic and psychiatric disorders. Accordingly, the goal of our review is to highlight potential thematic/functional linkages of pathophysiological alterations in gut microbiota and bidirectional gut-brain signaling pathways with special emphasis on the potential roles of gut dysbiosis on the pathophysiology of psychiatric illnesses. We provide critical discussion of putative thematic linkages of Parkinson's disease (PD) data sets to similar pathophysiological events as potential causative factors in the development and persistence of diverse psychiatric illnesses. Finally, we include a concise review of preclinical paradigms that involve immunologically-induced GI deficits and dysbiosis of maternal microflora that are functionally linked to impaired neurodevelopmental processes leading to affective behavioral syndromes in the offspring.}, }
@article {pmid29795809, year = {2018}, author = {McDonald, D and Hyde, E and Debelius, JW and Morton, JT and Gonzalez, A and Ackermann, G and Aksenov, AA and Behsaz, B and Brennan, C and Chen, Y and DeRight Goldasich, L and Dorrestein, PC and Dunn, RR and Fahimipour, AK and Gaffney, J and Gilbert, JA and Gogul, G and Green, JL and Hugenholtz, P and Humphrey, G and Huttenhower, C and Jackson, MA and Janssen, S and Jeste, DV and Jiang, L and Kelley, ST and Knights, D and Kosciolek, T and Ladau, J and Leach, J and Marotz, C and Meleshko, D and Melnik, AV and Metcalf, JL and Mohimani, H and Montassier, E and Navas-Molina, J and Nguyen, TT and Peddada, S and Pevzner, P and Pollard, KS and Rahnavard, G and Robbins-Pianka, A and Sangwan, N and Shorenstein, J and Smarr, L and Song, SJ and Spector, T and Swafford, AD and Thackray, VG and Thompson, LR and Tripathi, A and Vázquez-Baeza, Y and Vrbanac, A and Wischmeyer, P and Wolfe, E and Zhu, Q and ,  and Knight, R}, title = {American Gut: an Open Platform for Citizen Science Microbiome Research.}, journal = {mSystems}, volume = {3}, number = {3}, pages = {}, pmid = {29795809}, issn = {2379-5077}, support = {//Wellcome Trust/United Kingdom ; P30 DK042086/DK/NIDDK NIH HHS/United States ; P30 DK043351/DK/NIDDK NIH HHS/United States ; }, abstract = {Although much work has linked the human microbiome to specific phenotypes and lifestyle variables, data from different projects have been challenging to integrate and the extent of microbial and molecular diversity in human stool remains unknown. Using standardized protocols from the Earth Microbiome Project and sample contributions from over 10,000 citizen-scientists, together with an open research network, we compare human microbiome specimens primarily from the United States, United Kingdom, and Australia to one another and to environmental samples. Our results show an unexpected range of beta-diversity in human stool microbiomes compared to environmental samples; demonstrate the utility of procedures for removing the effects of overgrowth during room-temperature shipping for revealing phenotype correlations; uncover new molecules and kinds of molecular communities in the human stool metabolome; and examine emergent associations among the microbiome, metabolome, and the diversity of plants that are consumed (rather than relying on reductive categorical variables such as veganism, which have little or no explanatory power). We also demonstrate the utility of the living data resource and cross-cohort comparison to confirm existing associations between the microbiome and psychiatric illness and to reveal the extent of microbiome change within one individual during surgery, providing a paradigm for open microbiome research and education. IMPORTANCE We show that a citizen science, self-selected cohort shipping samples through the mail at room temperature recaptures many known microbiome results from clinically collected cohorts and reveals new ones. Of particular interest is integrating n = 1 study data with the population data, showing that the extent of microbiome change after events such as surgery can exceed differences between distinct environmental biomes, and the effect of diverse plants in the diet, which we confirm with untargeted metabolomics on hundreds of samples.}, }
@article {pmid29795140, year = {2018}, author = {Porter, CM and Shrestha, E and Peiffer, LB and Sfanos, KS}, title = {The microbiome in prostate inflammation and prostate cancer.}, journal = {Prostate cancer and prostatic diseases}, volume = {21}, number = {3}, pages = {345-354}, doi = {10.1038/s41391-018-0041-1}, pmid = {29795140}, issn = {1476-5608}, mesh = {Disease Progression ; Humans ; Male ; Microbiota/*physiology ; Prostate/*microbiology/pathology ; Prostatic Hyperplasia/immunology/*microbiology/pathology ; Prostatic Neoplasms/immunology/*microbiology/pathology ; Prostatitis/immunology/*microbiology/pathology ; Xenobiotics/immunology/metabolism ; }, abstract = {BACKGROUND: The human microbiome may influence prostate cancer initiation and/or progression through both direct and indirect interactions. To date, the majority of studies have focused on direct interactions including the influence of prostate infections on prostate cancer risk and, more recently, on the composition of the urinary microbiome in relation to prostate cancer. Less well understood are indirect interactions of the microbiome with prostate cancer, such as the influence of the gastrointestinal or oral microbiota on pro- or anti-carcinogenic xenobiotic metabolism, and treatment response.<br><br>METHODS: We review the literature to date on direct and indirect interactions of the microbiome with prostate inflammation and prostate cancer.<br><br>RESULTS: Emerging studies indicate that the microbiome can influence prostate inflammation in relation to benign prostate conditions such as prostatitis/chronic pelvic pain syndrome and benign prostatic hyperplasia, as well as in prostate cancer. We provide evidence that the human microbiome present at multiple anatomic sites (urinary tract, gastrointestinal tract, oral cavity, etc.) may play an important role in prostate health and disease.<br><br>CONCLUSIONS: In health, the microbiome encourages homeostasis and helps educate the immune system. In dysbiosis, a systemic inflammatory state may be induced, predisposing remote anatomical sites to disease, including cancer. The microbiome's ability to affect systemic hormone levels may also be important, particularly in a disease such as prostate cancer that is dually affected by estrogen and androgen levels. Due to the complexity of the potential interconnectedness between prostate cancer and the microbiome, it is vital to further explore and understand the relationships that are involved.}, }
@article {pmid29789680, year = {2018}, author = {Banerjee, S and Schlaeppi, K and van der Heijden, MGA}, title = {Keystone taxa as drivers of microbiome structure and functioning.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {9}, pages = {567-576}, doi = {10.1038/s41579-018-0024-1}, pmid = {29789680}, issn = {1740-1534}, mesh = {Animals ; Bacteria/classification/isolation &amp; purification/metabolism ; *Environmental Microbiology ; Humans ; *Microbiota ; }, abstract = {Microorganisms have a pivotal role in the functioning of ecosystems. Recent studies have shown that microbial communities harbour keystone taxa, which drive community composition and function irrespective of their abundance. In this Opinion article, we propose a definition of keystone taxa in microbial ecology and summarize over 200 microbial keystone taxa that have been identified in soil, plant and marine ecosystems, as well as in the human microbiome. We explore the importance of keystone taxa and keystone guilds for microbiome structure and functioning and discuss the factors that determine their distribution and activities.}, }
@article {pmid29786923, year = {2019}, author = {Bandara, HMHN and Panduwawala, CP and Samaranayake, LP}, title = {Biodiversity of the human oral mycobiome in health and disease.}, journal = {Oral diseases}, volume = {25}, number = {2}, pages = {363-371}, doi = {10.1111/odi.12899}, pmid = {29786923}, issn = {1601-0825}, mesh = {*Biodiversity ; Humans ; Immunocompromised Host ; Mouth/*microbiology/physiology ; Mouth Diseases/*microbiology ; *Mycobiome ; Mycological Typing Techniques ; Mycoses/*microbiology ; Saliva/microbiology ; }, abstract = {The organisms that colonize the human body over a lifetime are diverse, extensive and gargantuan. A fair proportion of the microbiota that constitutes this human microbiome live within our oral cavities mostly as harmonious associates causing only sporadic disease. An important core constituent of the microbiome is the mycobiome, representing various fungal genera. Up until recently, only a few species of fungi, mainly Candida species, were thought to constitute the human oral mycobiome. The reasons for this are manifold, although the uncultivable nature of many fungi in conventional laboratory media, and their complex genetic composition seem to be the major factors which eluded their detection over the years. Nevertheless, recent advances in computing and high-throughput sequencing such as next-generation sequencing (NGS) platforms have provided us a panoramic view of a totally new world of fungi that are human oral cohabitués. Their diversity is perplexing, and functionality yet to be deciphered. Here, we provide a glimpse of what is currently known of the oral mycobiome, in health and disease, with some future perspectives.}, }
@article {pmid29781826, year = {2018}, author = {Swami, U and Zakharia, Y and Zhang, J}, title = {Understanding Microbiome Effect on Immune Checkpoint Inhibition in Lung Cancer: Placing the Puzzle Pieces Together.}, journal = {Journal of immunotherapy (Hagerstown, Md. : 1997)}, volume = {41}, number = {8}, pages = {359-360}, doi = {10.1097/CJI.0000000000000232}, pmid = {29781826}, issn = {1537-4513}, support = {P30 CA086862/CA/NCI NIH HHS/United States ; }, abstract = {Over the past couple of years, human microbiome has received increasing attention as a regulator and predictor of response to the therapies of various diseases. It is speculated that manipulating gut microbiome can modify response to cancer immunotherapies as well. Through this review, we have critically analyzed our current understanding of gut microbiome as a modulator of immunotherapies in lung cancer, explained conflicting data, evaluated current gaps and extrapolated our present knowledge to generate directions for future investigations.}, }
@article {pmid29773467, year = {2018}, author = {Daliri, EB and Tango, CN and Lee, BH and Oh, DH}, title = {Human microbiome restoration and safety.}, journal = {International journal of medical microbiology : IJMM}, volume = {308}, number = {5}, pages = {487-497}, doi = {10.1016/j.ijmm.2018.05.002}, pmid = {29773467}, issn = {1618-0607}, mesh = {Anti-Bacterial Agents ; Bacteria/classification/isolation &amp; purification ; Diet ; Dysbiosis/*therapy ; Fecal Microbiota Transplantation/*adverse effects/methods ; Gastrointestinal Microbiome/*physiology ; Humans ; Probiotics/*administration &amp; dosage ; }, abstract = {The human gut microbiome consists of many bacteria which are in symbiotic relationship with human beings. The gut microbial metabolism, as well as the microbial-host co-metabolism, has been found to greatly influence health and disease. Factors such as diet, antibiotic use and lifestyle have been associated with alterations in the gut microbial community and may result in several pathological conditions. For this reason, several strategies including fecal microbiota transplant and probiotic administration have been applied and proven to be feasible and effective in restoring the gut microbiota in humans. Yet, safety concerns such as potential health risks that may arise from such interventions and how these strategies are regulated need to be addressed. Also, it will be important to know if these microbiome restoration strategies can have a profound impact on health. This review provides an overview of our current knowledge of the microbiome restoration strategies and safety issues on how these strategies are regulated.}, }
@article {pmid29765359, year = {2018}, author = {Ingala, MR and Simmons, NB and Wultsch, C and Krampis, K and Speer, KA and Perkins, SL}, title = {Comparing Microbiome Sampling Methods in a Wild Mammal: Fecal and Intestinal Samples Record Different Signals of Host Ecology, Evolution.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {803}, pmid = {29765359}, issn = {1664-302X}, abstract = {The gut microbiome is a community of host-associated symbiotic microbes that fulfills multiple key roles in host metabolism, immune function, and tissue development. Given the ability of the microbiome to impact host fitness, there is increasing interest in studying the microbiome of wild animals to better understand these communities in the context of host ecology and evolution. Human microbiome research protocols are well established, but wildlife microbiome research is still a developing field. Currently, there is no standardized set of best practices guiding the collection of microbiome samples from wildlife. Gut microflora are typically sampled either by fecal collection, rectal swabbing, or by destructively sampling the intestinal contents of the host animal. Studies rarely include more than one sampling technique and no comparison of these methods currently exists for a wild mammal. Although some studies have hypothesized that the fecal microbiome is a nested subset of the intestinal microbiome, this hypothesis has not been formally tested. To address these issues, we examined guano (feces) and distal intestinal mucosa from 19 species of free-ranging bats from Lamanai, Belize, using 16S rRNA amplicon sequencing to compare microbial communities across sample types. We found that the diversity and composition of intestine and guano samples differed substantially. In addition, we conclude that signatures of host evolution are retained by studying gut microbiomes based on mucosal tissue samples, but not fecal samples. Conversely, fecal samples retained more signal of host diet than intestinal samples. These results suggest that fecal and intestinal sampling methods are not interchangeable, and that these two microbiotas record different information about the host from which they are isolated.}, }
@article {pmid29760467, year = {2018}, author = {Xian, P and Xuedong, Z and Xin, X and Yuqing, L and Yan, L and Jiyao, L and Xiaoquan, S and Shi, H and Jian, X and Ga, L}, title = {The Oral Microbiome Bank of China.}, journal = {International journal of oral science}, volume = {10}, number = {2}, pages = {16}, pmid = {29760467}, issn = {2049-3169}, mesh = {China ; Humans ; *Microbiota ; Mouth/*microbiology ; }, abstract = {The human microbiome project (HMP) promoted further understanding of human oral microbes. However, research on the human oral microbiota has not made as much progress as research on the gut microbiota. Currently, the causal relationship between the oral microbiota and oral diseases remains unclear, and little is known about the link between the oral microbiota and human systemic diseases. To further understand the contribution of the oral microbiota in oral diseases and systemic diseases, a Human Oral Microbiome Database (HOMD) was established in the US. The HOMD includes 619 taxa in 13 phyla, and most of the microorganisms are from American populations. Due to individual differences in the microbiome, the HOMD does not reflect the Chinese oral microbial status. Herein, we established a new oral microbiome database-the Oral Microbiome Bank of China (OMBC, http://www.sklod.org/ombc). Currently, the OMBC includes information on 289 bacterial strains and 720 clinical samples from the Chinese population, along with lab and clinical information. The OMBC is the first curated description of a Chinese-associated microbiome; it provides tools for use in investigating the role of the oral microbiome in health and diseases, and will give the community abundant data and strain information for future oral microbial studies.}, }
@article {pmid29756665, year = {2018}, author = {Watson, E and Reid, G}, title = {Metabolomics as a clinical testing method for the diagnosis of vaginal dysbiosis.}, journal = {American journal of reproductive immunology (New York, N.Y. : 1989)}, volume = {80}, number = {2}, pages = {e12979}, doi = {10.1111/aji.12979}, pmid = {29756665}, issn = {1600-0897}, abstract = {Microbes play an important role in vaginal health, with lactobacilli a particularly abundant species. When dysbiosis occurs, the tools to determine whether it is a condition such as bacterial vaginosis, and whether it warrants antibiotic treatment, are currently suboptimal. We propose that standardization and implementation of an affordable metabolomics-based diagnostic technique could reduce instances of false positives, stress associated with misdiagnosis, and potentially save time and money. Basing diagnosis on the detection of pH elevated above 4.5 and specific polyamines could provide a better method to assist a physician determine whether treatment is warranted.}, }
@article {pmid29756604, year = {2018}, author = {Stefano, GB and Kream, RM}, title = {Alkaloids, Nitric Oxide, and Nitrite Reductases: Evolutionary Coupling as Key Regulators of Cellular Bioenergetics with Special Relevance to the Human Microbiome.}, journal = {Medical science monitor : international medical journal of experimental and clinical research}, volume = {24}, number = {}, pages = {3153-3158}, pmid = {29756604}, issn = {1643-3750}, mesh = {Alkaloids/*metabolism ; *Biological Evolution ; *Energy Metabolism ; Humans ; *Microbiota ; Nitric Oxide/*metabolism ; Nitrite Reductases/*metabolism ; }, abstract = {Typical alkaloids expressed by prokaryotic and eukaryotic cells are small heterocyclic compounds containing weakly basic nitrogen groups that are critically important for mediating essential biological activities. The prototype opiate alkaloid morphine represents a low molecular mass heterocyclic compound that has been evolutionarily fashioned from a relatively restricted role as a secreted antimicrobial phytoalexin into a broad spectrum regulatory molecule. As an essential corollary, positive evolutionary pressure has driven the development of a cognate 6-transmembrane helical (TMH) domain μ3 opiate receptor that is exclusively responsive to morphine and related opiate alkaloids. A key aspect of &quot;morphinergic&quot; signaling mediated by μ3 opiate receptor activation is its functional coupling with regulatory pathways utilizing constitutive nitric oxide (NO) as a signaling molecule. Importantly, tonic and phasic intra-mitochondrial NO production exerts profound inhibitory effects on the rate of electron transport, H+ pumping, and O2 consumption. Given the pluripotent role of NO as a selective, temporally-defined chemical regulator of mitochondrial respiration and cellular bioenergetics, the expansion of prokaryotic denitrification systems into mitochondrial NO/nitrite cycling complexes represents a series of evolutionary modifications of existential proportions. Presently, our short review provides selective discussion of evolutionary development of morphine, opiate alkaloids, μ3 opiate receptors, and NO systems, within the perspectives of enhanced mitochondrial function, cellular bioenergetics, and the human microbiome.}, }
@article {pmid29753695, year = {2018}, author = {Chu, DM and Seferovic, M and Pace, RM and Aagaard, KM}, title = {The microbiome in preterm birth.}, journal = {Best practice &amp; research. Clinical obstetrics &amp; gynaecology}, volume = {52}, number = {}, pages = {103-113}, doi = {10.1016/j.bpobgyn.2018.03.006}, pmid = {29753695}, issn = {1532-1932}, mesh = {Female ; Humans ; Lactobacillus/metabolism ; Longitudinal Studies ; *Microbiota ; Placenta/microbiology ; Pregnancy ; Premature Birth/*microbiology ; Vagina/microbiology ; }, abstract = {The microbiome is thought to play a role in the maintenance of a healthy pregnancy and thus may either contribute to or protect from preterm birth. Study of the human microbiome has been aided by metagenomic sequencing approaches, providing greater insight into the commensal bacteria that coexist in and on our bodies. The vaginal microbiome has been the most widely studied, though there have been recent efforts to explore the gut, cervical-vaginal, placental and oral microbiomes in the further search of etiologies of preterm birth. To date, a specific microbiome community or microorganism has yet to be reliably associated with preterm birth. This is partly due to the fact that the 'normal' constituents' microbiome can vary widely between healthy individuals. Before our knowledge of the microbiome can be utilized and applied in clinical practice, a greater understanding of the 'healthy' microbiome must be achieved. In particular, we must first appreciate how our microbes influence our biology to promote a healthy pregnancy or alternately render preterm birth.}, }
@article {pmid29747892, year = {2018}, author = {Valentine, G and Chu, DM and Stewart, CJ and Aagaard, KM}, title = {Relationships Between Perinatal Interventions, Maternal-Infant Microbiomes, and Neonatal Outcomes.}, journal = {Clinics in perinatology}, volume = {45}, number = {2}, pages = {339-355}, doi = {10.1016/j.clp.2018.01.008}, pmid = {29747892}, issn = {1557-9840}, support = {F32 DK101179/DK/NIDDK NIH HHS/United States ; }, mesh = {Adult ; Female ; Fetal Diseases/*microbiology ; Humans ; *Infant Health ; Infant, Newborn ; Infant, Newborn, Diseases/*microbiology/therapy ; Male ; *Maternal Health ; Microbiota/immunology/*physiology ; Perinatal Care/methods ; Pregnancy ; Premature Birth/*microbiology ; Prenatal Care/methods ; Probiotics/administration &amp; dosage ; }, abstract = {The human microbiome acquires its vastness and diversity over a relatively short time period during development. Much is unknown, however, about the precise prenatal versus postnatal timing or its sources and determinants. Given early evidence of a role for influences during pregnancy and early neonatal and infant life on the microbiome and subsequent metabolic health, research investigating the development and shaping of the microbiome in the fetus and neonate is an important arena for study. This article reviews the relevant available literature and future questions on what shapes the microbiome during early development and mechanisms for doing so.}, }
@article {pmid29743478, year = {2018}, author = {Olde Loohuis, LM and Mangul, S and Ori, APS and Jospin, G and Koslicki, D and Yang, HT and Wu, T and Boks, MP and Lomen-Hoerth, C and Wiedau-Pazos, M and Cantor, RM and de Vos, WM and Kahn, RS and Eskin, E and Ophoff, RA}, title = {Transcriptome analysis in whole blood reveals increased microbial diversity in schizophrenia.}, journal = {Translational psychiatry}, volume = {8}, number = {1}, pages = {96}, pmid = {29743478}, issn = {2158-3188}, support = {R01 MH090553/MH/NIMH NIH HHS/United States ; R01 NS058980/NS/NINDS NIH HHS/United States ; R01 MH078075/MH/NIMH NIH HHS/United States ; R21 MH098035/MH/NIMH NIH HHS/United States ; T32 NS048004/NS/NINDS NIH HHS/United States ; K25 HL080079/HL/NHLBI NIH HHS/United States ; U01 DA024417/DA/NIDA NIH HHS/United States ; P01 HL030568/HL/NHLBI NIH HHS/United States ; R01 GM083198/GM/NIGMS NIH HHS/United States ; R01 ES021801/ES/NIEHS NIH HHS/United States ; R01 MH101782/MH/NIMH NIH HHS/United States ; R01 ES022282/ES/NIEHS NIH HHS/United States ; }, mesh = {Adult ; Amyotrophic Lateral Sclerosis/blood/microbiology ; Bipolar Disorder/blood/microbiology ; Female ; Gene Expression Profiling ; Humans ; Male ; *Microbiota ; Middle Aged ; Schizophrenia/*blood/*microbiology ; Sequence Analysis, RNA ; Young Adult ; }, abstract = {The role of the human microbiome in health and disease is increasingly appreciated. We studied the composition of microbial communities present in blood across 192 individuals, including healthy controls and patients with three disorders affecting the brain: schizophrenia, amyotrophic lateral sclerosis, and bipolar disorder. By using high-quality unmapped RNA sequencing reads as candidate microbial reads, we performed profiling of microbial transcripts detected in whole blood. We were able to detect a wide range of bacterial and archaeal phyla in blood. Interestingly, we observed an increased microbial diversity in schizophrenia patients compared to the three other groups. We replicated this finding in an independent schizophrenia case-control cohort. This increased diversity is inversely correlated with estimated cell abundance of a subpopulation of CD8+ memory T cells in healthy controls, supporting a link between microbial products found in blood, immunity and schizophrenia.}, }
@article {pmid29743119, year = {2018}, author = {Zolfo, M and Asnicar, F and Manghi, P and Pasolli, E and Tett, A and Segata, N}, title = {Profiling microbial strains in urban environments using metagenomic sequencing data.}, journal = {Biology direct}, volume = {13}, number = {1}, pages = {9}, pmid = {29743119}, issn = {1745-6150}, mesh = {Acinetobacter/genetics ; Genome, Bacterial/genetics ; Humans ; Metagenome/*genetics ; Metagenomics/*methods ; Microbiota/genetics ; Phylogeny ; }, abstract = {BACKGROUND: The microbial communities populating human and natural environments have been extensively characterized with shotgun metagenomics, which provides an in-depth representation of the microbial diversity within a sample. Microbes thriving in urban environments may be crucially important for human health, but have received less attention than those of other environments. Ongoing efforts started to target urban microbiomes at a large scale, but the most recent computational methods to profile these metagenomes have never been applied in this context. It is thus currently unclear whether such methods, that have proven successful at distinguishing even closely related strains in human microbiomes, are also effective in urban settings for tasks such as cultivation-free pathogen detection and microbial surveillance. Here, we aimed at a) testing the currently available metagenomic profiling tools on urban metagenomics; b) characterizing the organisms in urban environment at the resolution of single strain and c) discussing the biological insights that can be inferred from such methods.<br><br>RESULTS: We applied three complementary methods on the 1614 metagenomes of the CAMDA 2017 challenge. With MetaMLST we identified 121 known sequence-types from 15 species of clinical relevance. For instance, we identified several Acinetobacter strains that were close to the nosocomial opportunistic pathogen A. nosocomialis. With StrainPhlAn, a generalized version of the MetaMLST approach, we inferred the phylogenetic structure of Pseudomonas stutzeri strains and suggested that the strain-level heterogeneity in environmental samples is higher than in the human microbiome. Finally, we also probed the functional potential of the different strains with PanPhlAn. We further showed that SNV-based and pangenome-based profiling provide complementary information that can be combined to investigate the evolutionary trajectories of microbes and to identify specific genetic determinants of virulence and antibiotic resistances within closely related strains.<br><br>CONCLUSION: We show that strain-level methods developed primarily for the analysis of human microbiomes can be effective for city-associated microbiomes. In fact, (opportunistic) pathogens can be tracked and monitored across many hundreds of urban metagenomes. However, while more effort is needed to profile strains of currently uncharacterized species, this work poses the basis for high-resolution analyses of microbiomes sampled in city and mass transportation environments.<br><br>REVIEWERS: This article was reviewed by Alexandra Bettina Graf, Daniel Huson and Trevor Cickovski.}, }
@article {pmid29739953, year = {2018}, author = {Ma, ZS}, title = {Diversity time-period and diversity-time-area relationships exemplified by the human microbiome.}, journal = {Scientific reports}, volume = {8}, number = {1}, pages = {7214}, pmid = {29739953}, issn = {2045-2322}, abstract = {We extend the ecological laws of species-time relationship (STR) and species-time-area relationship (STAR) to general diversity time-period relationship (DTR) and diversity-time-area relationship (DTAR), and test the extensions with the human vaginal microbiome datasets by building 1460 DTR/DTAR models. Our extensions were inspired by the observation that Hill numbers, well regarded as the most appropriate measure of alpha-diversity and also particularly suitable for multiplicative beta-diversity partitioning, are actually in the units of effective species, and therefore, should be able to substitute for species in the STR and STAR. We found that the traditional power law (PL) model is only applicable for DTR at diversity order zero (i.e., species richness); at higher diversity orders (q = 1-4), the power law with exponent cutoff (PLEC) and power law with inverse exponent cutoff (PLIEC) are more appropriate. In particular, PLEC has an advantage over PLIEC in predicting maximal accumulation diversity (MAD) over time. In fact, with the DTR extensions, we can construct DTR and MAD profiles. To the best of our knowledge, this is the first comprehensive investigation of the DTR/DTAR in human microbiome. Methodologically, our DTR/DTAR profiles can characterize general diversity scaling beyond species richness, covering both alpha- and beta-diversity regimes across different diversity orders.}, }
@article {pmid29737047, year = {2018}, author = {Zhao, N and Zhan, X and Guthrie, KA and Mitchell, CM and Larson, J}, title = {Generalized Hotelling's test for paired compositional data with application to human microbiome studies.}, journal = {Genetic epidemiology}, volume = {42}, number = {5}, pages = {459-469}, doi = {10.1002/gepi.22127}, pmid = {29737047}, issn = {1098-2272}, mesh = {Computer Simulation ; Databases as Topic ; Female ; Humans ; *Microbiota ; *Models, Genetic ; Postmenopause ; Vagina/microbiology ; }, abstract = {The human microbiome is a dynamic system that changes due to diseases, medication, change in diet, etc. The paired design is a common approach to evaluate the microbial changes while controlling for the inherent differences between people. For example, microbiome data may be collected from the same individuals before and after a treatment. Two challenges exist in analyzing this type of data. First, microbiome data are compositional such that the reads for all taxa in each sample are constrained to sum to a constant. Second, the number of taxa can be much larger than the sample size. Few statistical methods exist to analyze such data besides methods that test one taxon at a time. In this paper, we propose to first conduct a log-ratio transformation of the compositions, and then develop a generalized Hotelling's test (GHT) to evaluate whether the average microbiome compositions are equivalent in the paired samples. We replace the sample covariance matrix in standard Hotelling's statistic by a shrinkage-based covariance, calculated as a weighted average of the sample covariance and a positive definite target matrix. The optimal weighting can be obtained for many commonly used target matrices. We develop a permutation procedure to assess the statistical significance. Extensive simulations show that our proposed method has well-controlled type I error and better power than a few ad hoc approaches. We apply our method to examine the vaginal microbiome changes in response to treatments for menopausal hot flashes. An R package &quot; GHT&quot; is freely available at https://github.com/zhaoni153/GHT.}, }
@article {pmid29728386, year = {2018}, author = {Feng, S and Bootsma, M and McLellan, SL}, title = {Human-Associated Lachnospiraceae Genetic Markers Improve Detection of Fecal Pollution Sources in Urban Waters.}, journal = {Applied and environmental microbiology}, volume = {84}, number = {14}, pages = {}, pmid = {29728386}, issn = {1098-5336}, support = {R01 AI091829/AI/NIAID NIH HHS/United States ; }, abstract = {The human microbiome contains many organisms that could potentially be used as indicators of human fecal pollution. Here we report the development of two novel human-associated genetic marker assays that target organisms within the family Lachnospiraceae Next-generation sequencing of the V6 region of the 16S rRNA gene from sewage and animal stool samples identified 40 human-associated marker candidates with a robust signal in sewage and low or no occurrence in samples from nonhuman hosts. Two were chosen for quantitative PCR (qPCR) assay development using longer sequences (the V2 to V9 regions) generated from clone libraries. Validation of these assays with these markers, designated Lachno3 and Lachno12, was performed using fecal samples (n = 55) from cat, dog, pig, cow, deer, and gull sources, and the results were compared with those of established host-associated assays (the Lachno2 marker and two human Bacteroides markers, the HB and HF183/BacR287). Each of the established assays cross-reacted with samples from at least one other animal species, including animals common in urban areas. The Lachno3 and Lachno12 markers were primarily human associated; however, the Lachno12 marker demonstrated low levels of cross-reactivity with samples from select cows and nonspecific amplification with samples from pigs. This limitation may not be problematic when testing urban waters. These novel markers resolved ambiguous results from previous investigations of stormwater-impacted waters, demonstrating their utility. The complexity of the microbiome in humans and animals suggests that no single organism is strictly specific to humans, and the use of multiple complementary markers in combination will provide the highest resolution and specificity for assessing fecal pollution sources.IMPORTANCE Traditional fecal indicator bacteria do not distinguish animal from human fecal pollution, which is necessary to evaluate health risks and mitigate pollution sources. Assessing water in urban areas is challenging, since the water can be impacted by sewage, which has a high likelihood of carrying human pathogens, as well as pet and urban wildlife waste. We demonstrate that the Lachno3 and Lachno12 markers are human associated and highly specific for the detection of human fecal pollution from urban sources, offering reliable identification of fecal pollution sources in urban waters.}, }
@article {pmid29725592, year = {2018}, author = {Sigdel, TK and Mercer, N and Nandoe, S and Nicora, CD and Burnum-Johnson, K and Qian, WJ and Sarwal, MM}, title = {Urinary Virome Perturbations in Kidney Transplantation.}, journal = {Frontiers in medicine}, volume = {5}, number = {}, pages = {72}, pmid = {29725592}, issn = {2296-858X}, support = {P41 GM103493/GM/NIGMS NIH HHS/United States ; }, abstract = {The human microbiome is important for health and plays a role in essential metabolic functions and protection from certain pathogens. Conversely, dysbiosis of the microbiome is seen in the context of various diseases. Recent studies have highlighted that a complex microbial community containing hundreds of bacteria colonizes the healthy urinary tract, but little is known about the human urinary viruses in health and disease. To evaluate the human urinary virome in the context of kidney transplantation (tx), variations in the composition of the urinary virome were evaluated in urine samples from normal healthy volunteers as well as patients with kidney disease after they had undergone kidney tx. Liquid chromatography-mass spectrometry/mass spectrometry analysis was undertaken on a selected cohort of 142 kidney tx patients and normal healthy controls, from a larger biobank of 770 kidney biopsy matched urine samples. In addition to analysis of normal healthy control urine, the cohort of kidney tx patients had biopsy confirmed phenotype classification, coincident with the urine sample analyzed, of stable grafts (STA), acute rejection, BK virus nephritis, and chronic allograft nephropathy. We identified 37 unique viruses, 29 of which are being identified for the first time in human urine samples. The composition of the human urinary virome differs in health and kidney injury, and the distribution of viral proteins in the urinary tract may be further impacted by IS exposure, diet and environmental, dietary, or cutaneous exposure to various insecticides and pesticides.}, }
@article {pmid29724017, year = {2018}, author = {Avershina, E and Angell, IL and Simpson, M and Storrø, O and Øien, T and Johnsen, R and Rudi, K}, title = {Low Maternal Microbiota Sharing across Gut, Breast Milk and Vagina, as Revealed by 16S rRNA Gene and Reduced Metagenomic Sequencing.}, journal = {Genes}, volume = {9}, number = {5}, pages = {}, pmid = {29724017}, issn = {2073-4425}, abstract = {The maternal microbiota plays an important role in infant gut colonization. In this work we have investigated which bacterial species are shared across the breast milk, vaginal and stool microbiotas of 109 women shortly before and after giving birth using 16S rRNA gene sequencing and a novel reduced metagenomic sequencing (RMS) approach in a subgroup of 16 women. All the species predicted by the 16S rRNA gene sequencing were also detected by RMS analysis and there was good correspondence between their relative abundances estimated by both approaches. Both approaches also demonstrate a low level of maternal microbiota sharing across the population and RMS analysis identified only two species common to most women and in all sample types (Bifidobacterium longum and Enterococcus faecalis). Breast milk was the only sample type that had significantly higher intra- than inter- individual similarity towards both vaginal and stool samples. We also searched our RMS dataset against an in silico generated reference database derived from bacterial isolates in the Human Microbiome Project. The use of this reference-based search enabled further separation of Bifidobacterium longum into Bifidobacterium longum ssp. longum and Bifidobacterium longum ssp. infantis. We also detected the Lactobacillus rhamnosus GG strain, which was used as a probiotic supplement by some women, demonstrating the potential of RMS approach for deeper taxonomic delineation and estimation.}, }
@article {pmid29721973, year = {2018}, author = {Rowan, S and Taylor, A}, title = {The Role of Microbiota in Retinal Disease.}, journal = {Advances in experimental medicine and biology}, volume = {1074}, number = {}, pages = {429-435}, doi = {10.1007/978-3-319-75402-4_53}, pmid = {29721973}, issn = {0065-2598}, mesh = {Animals ; Conjunctiva/microbiology ; Cornea/microbiology ; Diabetic Retinopathy/microbiology/prevention &amp; control ; Disease Models, Animal ; Gastrointestinal Microbiome/drug effects/physiology ; Germ-Free Life ; Glaucoma/microbiology ; Humans ; Macular Degeneration/microbiology ; Metformin/pharmacology ; Mice ; Microbiota/*physiology ; Mouth/microbiology ; Retinal Diseases/*microbiology ; Uveitis/microbiology ; }, abstract = {The ten years since the first publications on the human microbiome project have brought enormous attention and insight into the role of the human microbiome in health and disease. Connections between populations of microbiota and ocular disease are now being established, and increased accessibility to microbiome research and insights into other diseases is expected to yield enormous information in the coming years. With the characterization of the ocular microbiome, important insights have already been made regarding corneal and conjunctival tissues. Roles for non-ocular microbiomes in complex retinal diseases are now being evaluated. For example, the gut microbiome has been implicated in the pathogenesis of uveitis. This short review will summarize the few studies linking gut or oral microbiota to diabetic retinopathy (DR), glaucoma, and age-related macular degeneration (AMD). We will also conjecture where the most significant findings still remain to be elucidated. Finally, we will propose the gut-retina axis, related but distinct from the gut-brain axis.}, }
@article {pmid29719941, year = {2018}, author = {Kwan, SE and Shaughnessy, RJ and Hegarty, B and Haverinen-Shaughnessy, U and Peccia, J}, title = {The reestablishment of microbial communities after surface cleaning in schools.}, journal = {Journal of applied microbiology}, volume = {125}, number = {3}, pages = {897-906}, doi = {10.1111/jam.13898}, pmid = {29719941}, issn = {1365-2672}, mesh = {Colony Count, Microbial ; DNA, Bacterial/isolation &amp; purification ; DNA, Fungal/isolation &amp; purification ; *Environmental Microbiology ; Equipment and Supplies/*microbiology ; Humans ; Infection Control ; *Schools ; }, abstract = {AIMS: The goal of this study was to quantify the indoor microbiome dynamics of bacterial and fungal communities on school desk surfaces during a cleaning intervention.<br><br>METHODS AND RESULTS: Quantitative PCR and DNA sequenced-based approaches were employed to describe microbial community dynamics on ten desk surfaces, spread across three schools, located in the Northeast region of the United States. Six samples were taken from each desk, one precleaning, and five postcleaning at 30 min, 1, 3, 7 and 21 days. Cleaning of the desks physically removed c. 50% of bacteria, fungi, and human cells and a full recovery of the surface microbial concentrations occurred within 2-5 days. This recovery period is much shorter than the schools' once per semester cleaning schedule. The dominant source of bacteria and fungi on desks at all time points came from the human microbiome (skin, oral cavity, and gut). More than 50% fungi on desks were members of genera that contain known allergens.<br><br>CONCLUSIONS: Microbial communities on these school desks are primarily generated and maintained from the deposition of human-associated bacteria and fungi. Current school surface cleaning protocols and cycles may be ineffective at reducing student exposure to fungal allergens and microbes of human origin.<br><br>Multiple students often share desks in schools. Results on the removal and reestablishment of microbial communities on these surfaces are critical for setting cleaning schedules and practices that effectively interrupt exposure to surface-associated pathogens and allergens.}, }
@article {pmid29718276, year = {2018}, author = {Reen, FJ and McGlacken, GP and O'Gara, F}, title = {The expanding horizon of alkyl quinolone signalling and communication in polycellular interactomes.}, journal = {FEMS microbiology letters}, volume = {365}, number = {9}, pages = {}, doi = {10.1093/femsle/fny076}, pmid = {29718276}, issn = {1574-6968}, mesh = {Animals ; Cystic Fibrosis/*microbiology ; Host-Pathogen Interactions ; Humans ; Microbial Interactions ; Pseudomonas Infections/*microbiology ; Pseudomonas aeruginosa/genetics/*metabolism ; Quinolones/*metabolism ; Signal Transduction ; }, abstract = {Population dynamics within natural ecosystems is underpinned by microbial diversity and the heterogeneity of host-microbe and microbe-microbe interactions. Small molecule signals that intersperse between species have been shown to govern many virulence-related processes in established and emerging pathogens. Understanding the capacity of microbes to decode diverse languages and adapt to the presence of 'non-self' cells will provide an important new direction to the understanding of the 'polycellular' interactome. Alkyl quinolones (AQs) have been described in the ESKAPE pathogen Pseudomonas aeruginosa, the primary agent associated with mortality in patients with cystic fibrosis and the third most prevalent nosocomial pathogen worldwide. The role of these molecules in governing the physiology and virulence of P. aeruginosa and other pathogens has received considerable attention, while a role in interspecies and interkingdom communication has recently emerged. Herein we discuss recent advances in our understanding of AQ signalling and communication in the context of microbe-microbe and microbe-host interactions. The integrated knowledge from these systems-based investigations will facilitate the development of new therapeutics based on the AQ framework that serves to disarm the pathogenesis of P. aeruginosa and competing pathogens.}, }
@article {pmid29715493, year = {2018}, author = {Rosado, MM and Aranburu, A and Scarsella, M and Cascioli, S and Giorda, E and Del Chierico, F and Mortera, SL and Mortari, EP and Petrini, S and Putignani, L and Carsetti, R}, title = {Spleen development is modulated by neonatal gut microbiota.}, journal = {Immunology letters}, volume = {199}, number = {}, pages = {1-15}, doi = {10.1016/j.imlet.2018.04.010}, pmid = {29715493}, issn = {1879-0542}, mesh = {Animals ; B-Lymphocytes/*immunology ; DNA-Binding Proteins/genetics ; Female ; Gastrointestinal Microbiome/*immunology ; Immunoglobulin A, Secretory/*immunology ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Mutant Strains ; Spleen/*growth &amp; development/*immunology ; T-Lymphocytes/immunology ; }, abstract = {The full development of the mammalian immune system occurs after birth upon exposure to non self-antigens. The gut is the first site of bacterial colonization where it is crucial to create the appropriate microenvironment able to balance effector or tolerogenic responses to external stimuli. It is a well-established fact that at mucosal sites bacteria play a key role in developing the immune system but we ignore how colonising bacteria impact the maturation of the spleen. Here we addressed this issue. Taking advantage of the fact that milk SIgA regulates bacterial colonization of the newborn intestine, we generated immunocompetent mice born either from IgA pro-efficient or IgA deficient females. Having demonstrated that SIgA in maternal milk modulates neonatal gut microbiota by promoting an increased diversity of the colonizing species we also found that immunocompetent pups, not exposed to milk SIgA, fail to properly develop the FDC network and primary follicles in the spleen compromising the response to T-dependent antigens. The presence of a less diverse microbiota with a higher representation of pathogenic species leads to a fast replenishment of the marginal zone and the IgM plasma cell compartment of the spleen as well as IgA plasma cells in the gut.}, }
@article {pmid29710488, year = {2018}, author = {Zhang, Y and Wang, X and Li, H and Ni, C and Du, Z and Yan, F}, title = {Human oral microbiota and its modulation for oral health.}, journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie}, volume = {99}, number = {}, pages = {883-893}, doi = {10.1016/j.biopha.2018.01.146}, pmid = {29710488}, issn = {1950-6007}, mesh = {Dental Caries/microbiology ; Humans ; *Microbiota ; Mouth/*microbiology ; Mouth Diseases/*microbiology ; Oral Health ; Periodontal Diseases/microbiology ; }, abstract = {The oral microbiome is an important part of the human microbiome. The oral cavity contains several significantly different niches with distinct microbial communities. A wide range of microorganisms inhabit the human oral cavity, including bacteria, fungi, viruses, archaea and protozoa. These microorganisms form a complex ecological community that influences oral and systemic health. The most prevalent oral diseases, dental caries and periodontal diseases, are microbiota-associated diseases. Moreover, increasing evidences have supported that many systemic diseases are associated with disturbances in the oral ecosystem, such as diabetes, cardiovascular diseases and tumors. The current control of dental plaque-related diseases is nonspecific and is centered on the removal of plaque by mechanical means. Due to this realization about the oral microbiome, several new methods based on the modulation of the microbiome that aim at maintaining and reestablishing a healthy oral ecosystem have been developed.}, }
@article {pmid29704918, year = {2018}, author = {Wilkinson, EM and Ilhan, ZE and Herbst-Kralovetz, MM}, title = {Microbiota-drug interactions: Impact on metabolism and efficacy of therapeutics.}, journal = {Maturitas}, volume = {112}, number = {}, pages = {53-63}, doi = {10.1016/j.maturitas.2018.03.012}, pmid = {29704918}, issn = {1873-4111}, mesh = {Animals ; Anti-Infective Agents/pharmacokinetics ; Anti-Inflammatory Agents/pharmacokinetics ; Antineoplastic Agents/pharmacokinetics ; Biotransformation ; *Drug Therapy ; Drug-Related Side Effects and Adverse Reactions/*metabolism ; Female ; Gastrointestinal Microbiome ; Humans ; Immunologic Factors/pharmacokinetics ; *Microbiota ; Vagina/microbiology ; }, abstract = {The microbiome not only represents a vital modifier of health and disease, but is a clinically important drug target. Therefore, study of the impact of the human microbiome on drug metabolism, toxicity and efficacy is urgently needed. This review focuses on gut and vaginal microbiomes, and the effect of those microbiomes or components thereof on the pharmacokinetics of specific chemotherapeutic agents, immunotherapies, anti-inflammatory and antimicrobial drugs. In some cases, the presence of specific bacterial species within the microbiome can alter the metabolism of certain drugs, such as chemotherapeutic agents and antiviral drugs. These microbiota-drug interactions are identified mostly through studies using germ-free or microbiome-depleted animal models, or by the administration of specific bacterial isolates. The biotransformation of drugs can cause drug-related toxicities; however, biotransformation also provides a mechanism by which drug developers could exploit host microbiota to create more site-specific drugs. Within this review we consider the importance of the route of drug administration and interactions with microbiota at various mucosal sites. Notably, we discuss the potential utility of bacterial therapeutics in altering the microbiome to enhance therapeutic efficacy and clinical outcomes in a personalized fashion. Based on the data to date, there is a clinically important relationship between microbiota and drug metabolism throughout the lifespan; therefore, profiling of the human microbiome will be essential in order to understand the mechanisms by which these microbiota-drug interactions occur and the degree to which this complex interplay affects drug efficacy.}, }
@article {pmid29693574, year = {2018}, author = {Del Chierico, F and Cardile, S and Pietrobattista, A and Liccardo, D and Russo, A and Candusso, M and Basso, MS and Grimaldi, C and Pansani, L and Bernaschi, P and Torre, G and Putignani, L}, title = {Liver Transplantation and Gut Microbiota Profiling in a Child Colonized by a Multi-Drug Resistant Klebsiella pneumoniae: A New Approach to Move from Antibiotic to &quot;Eubiotic&quot; Control of Microbial Resistance.}, journal = {International journal of molecular sciences}, volume = {19}, number = {5}, pages = {}, pmid = {29693574}, issn = {1422-0067}, mesh = {Anti-Bacterial Agents/pharmacology/therapeutic use ; Carbapenems/pharmacology/therapeutic use ; *Drug Resistance, Bacterial ; Female ; *Gastrointestinal Microbiome ; Humans ; Infant ; Klebsiella Infections/diagnosis/drug therapy/*microbiology ; Klebsiella pneumoniae/*drug effects/genetics/pathogenicity ; Liver Transplantation/*adverse effects ; Postoperative Complications/*diagnosis/drug therapy/*microbiology ; }, abstract = {The increase of microorganisms multi-drug resistant (MDR) to antibiotics (ATBs) is becoming a global emergency, especially in frail subjects. In chronic liver disease (LD) with indications for liver transplantation (LT), MDR colonization can significantly affect the LT outcome. However, no clear guidelines for microbial management are available. A novel approach toward MDR-colonized patients undergoing LT was developed at our Center refraining from ATBs use during the transplant waiting list, and use of an intensive perioperative prophylaxis cycle. This study aimed to couple clinical evaluation with monitoring of gut microbiota in a pediatric LD patient colonized with MDR Klebsiella pneumoniae (KP) who underwent LT. No peri-transplant complications were reported, and a decontamination from the MDR bacteria occurred during follow-up. Significant changes in gut microbiota, especially during ATB treatment, were reported by microbiota profiling. Patterns of Klebsiella predominance and microbiota diversity revealed opposite temporal trends, with Klebsiella ecological microbiota niches linked to ATB-driven selection. Our infection control program appeared to control complications following LT in an MDR-KP-colonized patient. The perioperative ATB regimen, acting as LT prophylaxis, triggered MDR-KP overgrowth and gut dysbiosis, but buffered infectious processes. Mechanisms modulating the gut ecosystem should be taken into account in MDR colonization clinical management.}, }
@article {pmid29692798, year = {2018}, author = {Roche-Lima, A and Carrasquillo-Carrión, K and Gómez-Moreno, R and Cruz, JM and Velázquez-Morales, DM and Rogozin, IB and Baerga-Ortiz, A}, title = {The Presence of Genotoxic and/or Pro-inflammatory Bacterial Genes in Gut Metagenomic Databases and Their Possible Link With Inflammatory Bowel Diseases.}, journal = {Frontiers in genetics}, volume = {9}, number = {}, pages = {116}, pmid = {29692798}, issn = {1664-8021}, support = {U54 MD007600/MD/NIMHD NIH HHS/United States ; R25 GM061838/GM/NIGMS NIH HHS/United States ; G12 RR003051/RR/NCRR NIH HHS/United States ; G12 MD007600/MD/NIMHD NIH HHS/United States ; R21 CA198963/CA/NCI NIH HHS/United States ; }, abstract = {Background: The human gut microbiota is a dynamic community of microorganisms that mediate important biochemical processes. Differences in the gut microbial composition have been associated with inflammatory bowel diseases (IBD) and other intestinal disorders. In this study, we quantified and compared the frequencies of eight genotoxic and/or pro-inflammatory bacterial genes found in metagenomic Whole Genome Sequences (mWGSs) of samples from individuals with IBD vs. a cohort of healthy human subjects. Methods: The eight selected gene sequences were clbN, clbB, cif, cnf-1, usp, tcpC from Escherichia coli, gelE from Enterococcus faecalis and murB from Akkermansia muciniphila. We also included the sequences for the conserved murB genes from E. coli and E. faecalis as markers for the presence of Enterobacteriaceae or Enterococci in the samples. The gene sequences were chosen based on their previously reported ability to disrupt normal cellular processes to either promote inflammation or to cause DNA damage in cultured cells or animal models, which could be linked to a role in IBD. The selected sequences were searched in three different mWGS datasets accessed through the Human Microbiome Project (HMP): a healthy cohort (N = 251), a Crohn's disease cohort (N = 60) and an ulcerative colitis cohort (N = 17). Results: Firstly, the sequences for the murB housekeeping genes from Enterobacteriaceae and Enterococci were more frequently found in the IBD cohorts (32% E. coli in IBD vs. 12% in healthy; 13% E. faecalis in IBD vs. 3% in healthy) than in the healthy cohort, confirming earlier reports of a higher presence of both of these taxa in IBD. For some of the sequences in our study, especially usp and gelE, their frequency was even more sharply increased in the IBD cohorts than in the healthy cohort, suggesting an association with IBD that is not easily explained by the increased presence of E. coli or E. faecalis in those samples. Conclusion: Our results suggest a significant association between the presence of some of these genotoxic or pro-inflammatory gene sequences and IBDs. In addition, these results illustrate the power and limitations of the HMP database in the detection of possible clinical correlations for individual bacterial genes.}, }
@article {pmid29686658, year = {2018}, author = {Quagliariello, A and Del Chierico, F and Russo, A and Reddel, S and Conte, G and Lopetuso, LR and Ianiro, G and Dallapiccola, B and Cardona, F and Gasbarrini, A and Putignani, L}, title = {Gut Microbiota Profiling and Gut-Brain Crosstalk in Children Affected by Pediatric Acute-Onset Neuropsychiatric Syndrome and Pediatric Autoimmune Neuropsychiatric Disorders Associated With Streptococcal Infections.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {675}, pmid = {29686658}, issn = {1664-302X}, abstract = {Pediatric acute-onset neuropsychiatric syndrome (PANS) and pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections syndrome (PANDAS) are conditions that impair brain normal neurologic function, resulting in the sudden onset of tics, obsessive-compulsive disorder, and other behavioral symptoms. Recent studies have emphasized the crosstalk between gut and brain, highlighting how gut composition can influence behavior and brain functions. Thus, the present study investigates the relationship between PANS/PANDAS and gut microbiota ecology. The gut composition of a cohort of 30 patients with PANS/PANDAS was analyzed and compared to control subjects using 16S rRNA-based metagenomics. Data were analyzed for their α- and β-diversity; differences in bacterial distribution were detected by Wilcoxon and LEfSe tests, while metabolic profile was predicted via PICRUSt software. These analyses demonstrate the presence of an altered bacterial community structure in PANS/PANDAS patients with respect to controls. In particular, ecological analysis revealed the presence of two main clusters of subjects based on age range. Thus, to avoid age bias, data from patients and controls were split into two groups: 4-8 years old and >9 years old. The younger PANS/PANDAS group was characterized by a strong increase in Bacteroidetes; in particular, Bacteroides, Odoribacter, and Oscillospira were identified as potential microbial biomarkers of this composition type. Moreover, this group exhibited an increase of several pathways concerning the modulation of the antibody response to inflammation within the gut as well as a decrease in pathways involved in brain function (i.e., SCFA, D-alanine and tyrosine metabolism, and the dopamine pathway). The older group of patients displayed a less uniform bacterial profile, thus impairing the identification of distinct biomarkers. Finally, Pearson's analysis between bacteria and anti-streptolysin O titer reveled a negative correlation between genera belonging to Firmicutes phylum and anti-streptolysin O while a positive correlation was observed with Odoribacter. In conclusion, this study suggests that streptococcal infections alter gut bacterial communities leading to a pro-inflammatory status through the selection of specific bacterial strains associated with gut inflammation and immune response activation. These findings highlight the possibility of studying bacterial biomarkers associated with this disorder and might led to novel potential therapeutic strategies.}, }
@article {pmid29685174, year = {2018}, author = {Fan, X and Peters, BA and Jacobs, EJ and Gapstur, SM and Purdue, MP and Freedman, ND and Alekseyenko, AV and Wu, J and Yang, L and Pei, Z and Hayes, RB and Ahn, J}, title = {Drinking alcohol is associated with variation in the human oral microbiome in a large study of American adults.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {59}, pmid = {29685174}, issn = {2049-2618}, support = {R01 CA159036/CA/NCI NIH HHS/United States ; U01CA182370/CA/NCI NIH HHS/United States ; R21CA183887/CA/NCI NIH HHS/United States ; Pancreas Cancer Action Network Career Development Award//American Association for Cancer Research/International ; P30CA016087/CA/NCI NIH HHS/United States ; R03CA159414/CA/NCI NIH HHS/United States ; R01CA159036/CA/NCI NIH HHS/United States ; R01CA164964/CA/NCI NIH HHS/United States ; R01 CA164964/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; *Alcohol Drinking ; Female ; Humans ; Male ; Metagenome ; Metagenomics ; *Microbiota ; Middle Aged ; Mouth/*microbiology ; Public Health Surveillance ; RNA, Ribosomal, 16S/genetics ; United States ; }, abstract = {BACKGROUND: Dysbiosis of the oral microbiome can lead to local oral disease and potentially to cancers of the head, neck, and digestive tract. However, little is known regarding exogenous factors contributing to such microbial imbalance.<br><br>RESULTS: We examined the impact of alcohol consumption on the oral microbiome in a cross-sectional study of 1044 US adults. Bacterial 16S rRNA genes from oral wash samples were amplified, sequenced, and assigned to bacterial taxa. We tested the association of alcohol drinking level (non-drinker, moderate drinker, or heavy drinker) and type (liquor, beer, or wine) with overall microbial composition and individual taxon abundance. The diversity of oral microbiota and overall bacterial profiles differed between heavy drinkers and non-drinkers (α-diversity richness p = 0.0059 and β-diversity unweighted UniFrac p = 0.0036), and abundance of commensal order Lactobacillales tends to be decreased with higher alcohol consumption (fold changes = 0.89 and 0.94 for heavy and moderate drinkers, p trend = 0.005 [q = 0.064]). Additionally, certain genera were enriched in subjects with higher alcohol consumption, including Actinomyces, Leptotrichia, Cardiobacterium, and Neisseria; some of these genera contain oral pathogens, while Neisseria can synthesize the human carcinogen acetaldehyde from ethanol. Wine drinkers may differ from non-drinkers in microbial diversity and profiles (α-diversity richness p = 0.048 and β-diversity unweighted UniFrac p = 0.059) after controlling for drinking amount, while liquor and beer drinkers did not. All significant differences between drinkers and non-drinkers remained after exclusion of current smokers.<br><br>CONCLUSIONS: Our results, from a large human study of alcohol consumption and the oral microbiome, indicate that alcohol consumption, and heavy drinking in particular, may influence the oral microbiome composition. These findings may have implications for better understanding the potential role that oral bacteria play in alcohol-related diseases.}, }
@article {pmid29682676, year = {2018}, author = {Cong, J and Zhang, X}, title = {How human microbiome talks to health and disease.}, journal = {European journal of clinical microbiology &amp; infectious diseases : official publication of the European Society of Clinical Microbiology}, volume = {37}, number = {9}, pages = {1595-1601}, pmid = {29682676}, issn = {1435-4373}, support = {2016M602094//China Postdoctoral Science Foundation/ ; 2016047//Qingdao Application Research Project/ ; 16-6-2-3-nsh//Qingdao People's Livelihood Science and Technology Program/ ; }, mesh = {Biomarkers ; Computational Biology ; Disease/*etiology ; Gastrointestinal Microbiome/genetics ; *Health ; Humans ; Microbiota/*genetics ; Mouth/microbiology ; Neoplasms/*therapy ; Skin/microbiology ; }, abstract = {Microbes are ubiquitous in the human body. They usually live in communities, and each of these communities has a distinct taxonomical structure. Due to its close relationship with human health and disease, the human microbiome has received great attention and is probably considered to be the most valuable biomarker in preventing and solving human diseases. In this paper, we first review the value of the human microbiome. Then, we focus on the role of the human microbiome in influencing human health and disease. Furthermore, we intensively discuss the relationship between intestinal microbiota and cancer therapy. Finally, we briefly summarize the significance of the human microbiome based on the development of sequencing and bioinformatic techniques.}, }
@article {pmid29675808, year = {2018}, author = {Ma, Y and Chen, H and Lan, C and Ren, J}, title = {Help, hope and hype: ethical considerations of human microbiome research and applications.}, journal = {Protein &amp; cell}, volume = {9}, number = {5}, pages = {404-415}, pmid = {29675808}, issn = {1674-8018}, mesh = {Biomedical Research/*ethics ; Humans ; *Microbiota ; Research Design/*standards ; }, }
@article {pmid29673211, year = {2018}, author = {Harsch, IA and Konturek, PC}, title = {The Role of Gut Microbiota in Obesity and Type 2 and Type 1 Diabetes Mellitus: New Insights into &quot;Old&quot; Diseases.}, journal = {Medical sciences (Basel, Switzerland)}, volume = {6}, number = {2}, pages = {}, pmid = {29673211}, issn = {2076-3271}, abstract = {The investigation of the human microbiome is the most rapidly expanding field in biomedicine. Early studies were undertaken to better understand the role of microbiota in carbohydrate digestion and utilization. These processes include polysaccharide degradation, glycan transport, glycolysis, and short-chain fatty acid production. Recent research has demonstrated that the intricate axis between gut microbiota and the host metabolism is much more complex. Gut microbiota&amp;mdash;depending on their composition&amp;mdash;have disease-promoting effects but can also possess protective properties. This review focuses on disorders of metabolic syndrome, with special regard to obesity as a prequel to type 2 diabetes, type 2 diabetes itself, and type 1 diabetes. In all these conditions, differences in the composition of the gut microbiota in comparison to healthy people have been reported. Mechanisms of the interaction between microbiota and host that have been characterized thus far include an increase in energy harvest, modulation of free fatty acids&amp;mdash;especially butyrate&amp;mdash;of bile acids, lipopolysaccharides, gamma-aminobutyric acid (GABA), an impact on toll-like receptors, the endocannabinoid system and &amp;ldquo;metabolic endotoxinemia&amp;rdquo; as well as &amp;ldquo;metabolic infection.&amp;rdquo; This review will also address the influence of already established therapies for metabolic syndrome and diabetes on the microbiota and the present state of attempts to alter the gut microbiota as a therapeutic strategy.}, }
@article {pmid29672703, year = {2018}, author = {Keshri, V and Panda, A and Levasseur, A and Rolain, JM and Pontarotti, P and Raoult, D}, title = {Phylogenomic Analysis of β-Lactamase in Archaea and Bacteria Enables the Identification of Putative New Members.}, journal = {Genome biology and evolution}, volume = {10}, number = {4}, pages = {1106-1114}, pmid = {29672703}, issn = {1759-6653}, mesh = {Anti-Bacterial Agents/adverse effects/therapeutic use ; Archaea/enzymology ; Bacteria/enzymology ; Carbapenems/*biosynthesis/chemistry ; Humans ; Metagenomics ; *Phylogeny ; beta-Lactamases/*genetics ; beta-Lactams/*metabolism ; }, abstract = {β-lactamases are enzymes which are commonly produced by bacteria and which degrade the β-lactam ring of β-lactam antibiotics, namely penicillins, cephalosporins, carbapenems, and monobactams, and inactivate these antibiotics. We performed a rational and comprehensive investigation of β-lactamases in different biological databases. In this study, we constructed hidden Markov model profiles as well as the ancestral sequence of four classes of β-lactamases (A, B, C, and D), which were used to identify potential β-lactamases from environmental metagenomic (1206), human microbiome metagenomic (6417), human microbiome reference genome (1310), and NCBI's nonredundant databases (44101). Our analysis revealed the existence of putative β-lactamases in the metagenomic databases, which appeared to be similar to the four different molecular classes (A-D). This is the first report on the large-scale phylogenetic diversity of new members of β-lactamases, and our results revealed that metagenomic database dark-matter contains β-lactamase-like antibiotic resistance genes.}, }
@article {pmid29669589, year = {2018}, author = {Coelho, LP and Kultima, JR and Costea, PI and Fournier, C and Pan, Y and Czarnecki-Maulden, G and Hayward, MR and Forslund, SK and Schmidt, TSB and Descombes, P and Jackson, JR and Li, Q and Bork, P}, title = {Similarity of the dog and human gut microbiomes in gene content and response to diet.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {72}, pmid = {29669589}, issn = {2049-2618}, support = {686070//Horizon 2020 Framework Programme (BE)/International ; }, mesh = {Animals ; *Diet ; Dogs ; Feces/microbiology ; *Gastrointestinal Microbiome ; Humans ; *Metagenome ; *Metagenomics/methods ; Mice ; *Microbiota ; Obesity ; Swine ; }, abstract = {BACKGROUND: Gut microbes influence their hosts in many ways, in particular by modulating the impact of diet. These effects have been studied most extensively in humans and mice. In this work, we used whole genome metagenomics to investigate the relationship between the gut metagenomes of dogs, humans, mice, and pigs.<br><br>RESULTS: We present a dog gut microbiome gene catalog containing 1,247,405 genes (based on 129 metagenomes and a total of 1.9 terabasepairs of sequencing data). Based on this catalog and taxonomic abundance profiling, we show that the dog microbiome is closer to the human microbiome than the microbiome of either pigs or mice. To investigate this similarity in terms of response to dietary changes, we report on a randomized intervention with two diets (high-protein/low-carbohydrate vs. lower protein/higher carbohydrate). We show that diet has a large and reproducible effect on the dog microbiome, independent of breed or sex. Moreover, the responses were in agreement with those observed in previous human studies.<br><br>CONCLUSIONS: We conclude that findings in dogs may be predictive of human microbiome results. In particular, a novel finding is that overweight or obese dogs experience larger compositional shifts than lean dogs in response to a high-protein diet.}, }
@article {pmid29668831, year = {2018}, author = {Maziarz, M and Pfeiffer, RM and Wan, Y and Gail, MH}, title = {Using standard microbiome reference groups to simplify beta-diversity analyses and facilitate independent validation.}, journal = {Bioinformatics (Oxford, England)}, volume = {34}, number = {19}, pages = {3249-3257}, pmid = {29668831}, issn = {1367-4811}, abstract = {Motivation: Comparisons of microbiome communities across populations are often based on pairwise distance measures (beta-diversity). Standard analyses (principal coordinate plots, permutation tests, kernel methods) require access to primary data if another investigator wants to add or compare independent data. We propose using standard reference measurements to simplify microbiome beta-diversity analyses, to make them more transparent, and to facilitate independent validation and comparisons across studies.<br><br>Results: Using stool and nasal reference sets from the Human Microbiome Project (HMP), we computed mean distances (actually Bray-Curtis or Pearson correlation dissimilarities) to each reference set for each new sample. Thus, each new sample has two mean distances that can be plotted and analyzed with classical statistical methods. To test the approach, we studied independent (not reference) HMP subjects. Simple Hotelling tests demonstrated statistically significant differences in mean distances to reference sets between all pairs of body sites (stool, skin, nasal, saliva and vagina) at the phylum, class, order, family and genus levels. Using the distance to a single reference set was usually sufficient, but using both reference sets always worked well. The use of reference sets simplifies standard analyses of beta-diversity and facilitates the independent validation and combining of such data because others can compute distances to the same reference sets. Moreover, standard statistical methods for survival analysis, logistic regression and other procedures can be applied to vectors of mean distances to reference sets, thereby greatly expanding the potential uses of beta-diversity information. More work is needed to identify the best reference sets for particular applications.<br><br>https://github.com/NCI-biostats/microbiome-fixed-reference.<br><br>Supplementary information: Supplementary data are available at Bioinformatics online.}, }
@article {pmid29668682, year = {2018}, author = {Hannigan, GD and Duhaime, MB and Koutra, D and Schloss, PD}, title = {Biogeography and environmental conditions shape bacteriophage-bacteria networks across the human microbiome.}, journal = {PLoS computational biology}, volume = {14}, number = {4}, pages = {e1006099}, pmid = {29668682}, issn = {1553-7358}, support = {T32AI007528/NH/NIH HHS/United States ; U01 AI124255/AI/NIAID NIH HHS/United States ; P30 DK034933/DK/NIDDK NIH HHS/United States ; P30DK034933/NH/NIH HHS/United States ; U01AI124255/NH/NIH HHS/United States ; U19AI09087/NH/NIH HHS/United States ; }, mesh = {Bacteria/*genetics ; *Bacterial Physiological Phenomena ; Bacteriophages/*genetics/*physiology ; Computational Biology ; Diet ; Humans ; Metagenomics ; Microbial Consortia/genetics/physiology ; Microbiota/*genetics/*physiology ; Models, Biological ; Phylogeography ; Skin/microbiology/virology ; }, abstract = {Viruses and bacteria are critical components of the human microbiome and play important roles in health and disease. Most previous work has relied on studying bacteria and viruses independently, thereby reducing them to two separate communities. Such approaches are unable to capture how these microbial communities interact, such as through processes that maintain community robustness or allow phage-host populations to co-evolve. We implemented a network-based analytical approach to describe phage-bacteria network diversity throughout the human body. We built these community networks using a machine learning algorithm to predict which phages could infect which bacteria in a given microbiome. Our algorithm was applied to paired viral and bacterial metagenomic sequence sets from three previously published human cohorts. We organized the predicted interactions into networks that allowed us to evaluate phage-bacteria connectedness across the human body. We observed evidence that gut and skin network structures were person-specific and not conserved among cohabitating family members. High-fat diets appeared to be associated with less connected networks. Network structure differed between skin sites, with those exposed to the external environment being less connected and likely more susceptible to network degradation by microbial extinction events. This study quantified and contrasted the diversity of virome-microbiome networks across the human body and illustrated how environmental factors may influence phage-bacteria interactive dynamics. This work provides a baseline for future studies to better understand system perturbations, such as disease states, through ecological networks.}, }
@article {pmid29666626, year = {2018}, author = {Ichinohe, T and Miyama, T and Kawase, T and Honjo, Y and Kitaura, K and Sato, H and Shin-I, T and Suzuki, R}, title = {Next-Generation Immune Repertoire Sequencing as a Clue to Elucidate the Landscape of Immune Modulation by Host-Gut Microbiome Interactions.}, journal = {Frontiers in immunology}, volume = {9}, number = {}, pages = {668}, pmid = {29666626}, issn = {1664-3224}, mesh = {Adaptive Immunity ; Animals ; Gastrointestinal Microbiome/*immunology ; *High-Throughput Nucleotide Sequencing ; Homeostasis ; Humans ; }, abstract = {The human immune system is a fine network consisted of the innumerable numbers of functional cells that balance the immunity and tolerance against various endogenous and environmental challenges. Although advances in modern immunology have revealed a role of many unique immune cell subsets, technologies that enable us to capture the whole landscape of immune responses against specific antigens have been not available to date. Acquired immunity against various microorganisms including host microbiome is principally founded on T cell and B cell populations, each of which expresses antigen-specific receptors that define a unique clonotype. Over the past several years, high-throughput next-generation sequencing has been developed as a powerful tool to profile T- and B-cell receptor repertoires in a given individual at the single-cell level. Sophisticated immuno-bioinformatic analyses by use of this innovative methodology have been already implemented in clinical development of antibody engineering, vaccine design, and cellular immunotherapy. In this article, we aim to discuss the possible application of high-throughput immune receptor sequencing in the field of nutritional and intestinal immunology. Although there are still unsolved caveats, this emerging technology combined with single-cell transcriptomics/proteomics provides a critical tool to unveil the previously unrecognized principle of host-microbiome immune homeostasis. Accumulation of such knowledge will lead to the development of effective ways for personalized immune modulation through deeper understanding of the mechanisms by which the intestinal environment affects our immune ecosystem.}, }
@article {pmid29665135, year = {2019}, author = {Ponziani, FR and Bhoori, S and Castelli, C and Putignani, L and Rivoltini, L and Del Chierico, F and Sanguinetti, M and Morelli, D and Paroni Sterbini, F and Petito, V and Reddel, S and Calvani, R and Camisaschi, C and Picca, A and Tuccitto, A and Gasbarrini, A and Pompili, M and Mazzaferro, V}, title = {Hepatocellular Carcinoma Is Associated With Gut Microbiota Profile and Inflammation in Nonalcoholic Fatty Liver Disease.}, journal = {Hepatology (Baltimore, Md.)}, volume = {69}, number = {1}, pages = {107-120}, doi = {10.1002/hep.30036}, pmid = {29665135}, issn = {1527-3350}, support = {//Italian Ministry of Education, Universities and Research/ ; }, abstract = {The gut-liver axis plays a pivotal role in the pathogenesis of nonalcoholic fatty liver disease (NAFLD), which is the third leading cause of hepatocellular carcinoma (HCC) worldwide. However, the link between gut microbiota and hepatocarcinogenesis remains to be clarified. The aim of this study was to explore what features of the gut microbiota are associated with HCC in patients with cirrhosis and NAFLD. A consecutive series of patients with NAFLD-related cirrhosis and HCC (group 1, 21 patients), NAFLD-related cirrhosis without HCC (group 2, 20 patients), and healthy controls (group 3, 20 patients) was studied for gut microbiota profile, intestinal permeability, inflammatory status, and circulating mononuclear cells. We finally constructed a model depicting the most relevant correlations among these features, possibly involved in hepatocarcinogenesis. Patients with HCC showed increased levels of fecal calprotectin, while intestinal permeability was similar to patients with cirrhosis but without HCC. Plasma levels of interleukin 8 (IL8), IL13, chemokine (C-C motif) ligand (CCL) 3, CCL4, and CCL5 were higher in the HCC group and associated with an activated status of circulating monocytes. The fecal microbiota of the whole group of patients with cirrhosis showed higher abundance of Enterobacteriaceae and Streptococcus and a reduction in Akkermansia. Bacteroides and Ruminococcaceae were increased in the HCC group, while Bifidobacterium was reduced. Akkermansia and Bifidobacterium were inversely correlated with calprotectin concentration, which in turn was associated with humoral and cellular inflammatory markers. A similar behavior was also observed for Bacteroides. Conclusion: Our results suggest that in patients with cirrhosis and NAFLD the gut microbiota profile and systemic inflammation are significantly correlated and can concur in the process of hepatocarcinogenesis.}, }
@article {pmid29659479, year = {2018}, author = {Sudhakara, P and Gupta, A and Bhardwaj, A and Wilson, A}, title = {Oral Dysbiotic Communities and Their Implications in Systemic Diseases.}, journal = {Dentistry journal}, volume = {6}, number = {2}, pages = {}, pmid = {29659479}, issn = {2304-6767}, support = {R03 DE026526/DE/NIDCR NIH HHS/United States ; }, abstract = {The human body supports the growth of a wide array of microbial communities in various niches such as the oral cavity, gastro-intestinal and urogenital tracts, and on the surface of the skin. These host associated microbial communities include yet-un-cultivable bacteria and are influenced by various factors. Together, these communities of bacteria are referred to as the human microbiome. Human oral microbiome consists of both symbionts and pathobionts. Deviation from symbiosis among the bacterial community leads to &amp;ldquo;dysbiosis&amp;rdquo;, a state of community disturbance. Dysbiosis occurs due to many confounding factors that predispose a shift in the composition and relative abundance of microbial communities. Dysbiotic communities have been a major cause for many microbiome related systemic infections. Such dysbiosis is directed by certain important pathogens called the &amp;ldquo;keystone pathogens&amp;rdquo;, which can modulate community microbiome variations. One such persistent infection is oral infection, mainly periodontitis, where a wide array of causal organisms have been implied to systemic infections such as cardio vascular disease, diabetes mellitus, rheumatoid arthritis, and Alzheimer&amp;rsquo;s disease. The keystone pathogens co-occur with many yet-cultivable bacteria and their interactions lead to dysbiosis. This has been the focus of recent research. While immune evasion is one of the major modes that leads to dysbiosis, new processes and new virulence factors of bacteria have been shown to be involved in this important process that determines a disease or health state. This review focuses on such dysbiotic communities, their interactions, and their virulence factors that predispose the host to other systemic implications.}, }
@article {pmid29658784, year = {2018}, author = {Popic, V and Kuleshov, V and Snyder, M and Batzoglou, S}, title = {Fast Metagenomic Binning via Hashing and Bayesian Clustering.}, journal = {Journal of computational biology : a journal of computational molecular cell biology}, volume = {25}, number = {7}, pages = {677-688}, doi = {10.1089/cmb.2017.0250}, pmid = {29658784}, issn = {1557-8666}, abstract = {We introduce GATTACA, a framework for fast unsupervised binning of metagenomic contigs. Similar to recent approaches, GATTACA clusters contigs based on their coverage profiles across a large cohort of metagenomic samples; however, unlike previous methods that rely on read mapping, GATTACA quickly estimates these profiles from kmer counts stored in a compact index. This approach can result in over an order of magnitude speedup, while matching the accuracy of earlier methods on synthetic and real data benchmarks. It also provides a way to index metagenomic samples (e.g., from public repositories such as the Human Microbiome Project) offline once and reuse them across experiments; furthermore, the small size of the sample indices allows them to be easily transferred and stored. Leveraging the MinHash technique, GATTACA also provides an efficient way to identify publicly available metagenomic data that can be incorporated into the set of reference metagenomes to further improve binning accuracy. Thus, enabling easy indexing and reuse of publicly available metagenomic data sets, GATTACA makes accurate metagenomic analyses accessible to a much wider range of researchers.}, }
@article {pmid29657964, year = {2018}, author = {Whiteson, KL}, title = {Vive la Persistence: Engineering Human Microbiomes in the 21st Century.}, journal = {mSystems}, volume = {3}, number = {2}, pages = {}, pmid = {29657964}, issn = {2379-5077}, abstract = {I imagine a future in which children grow up with healthy microbial communities. Engineering human microbiomes might actually be achievable in the near future, as we enter an era of hunting for human-adapted bacterial strains and phages. Furthermore, breath metabolites could allow us to track whether a probiotic colonizes persistently or a phage has knocked down a microbe of interest. Recent successes with probiotics, such as bifidobacteria that can break down human milk oligosaccharides, are making a future in which infants are intentionally colonized with health-promoting strains seem less unlikely. Viruses that infect bacteria, bacteriophages, are also important for human health both because of their role in the human microbiome and because of their potential for use in phage therapy. Monitoring the outcome of microbiome-focused interventions with breath volatile sampling is also on the horizon, which could mean real-time tracking of microbial metabolite production. Studies of early life during microbiome assembly, when the potential for effective interventions to reduce disease risk is greatest, are essential.}, }
@article {pmid29654837, year = {2018}, author = {Seekatz, AM and Theriot, CM and Rao, K and Chang, YM and Freeman, AE and Kao, JY and Young, VB}, title = {Restoration of short chain fatty acid and bile acid metabolism following fecal microbiota transplantation in patients with recurrent Clostridium difficile infection.}, journal = {Anaerobe}, volume = {53}, number = {}, pages = {64-73}, pmid = {29654837}, issn = {1095-8274}, support = {U19 AI090871/AI/NIAID NIH HHS/United States ; R21 AI120599/AI/NIAID NIH HHS/United States ; K01 GM109236/GM/NIGMS NIH HHS/United States ; U01 AI124255/AI/NIAID NIH HHS/United States ; R35 GM119438/GM/NIGMS NIH HHS/United States ; }, mesh = {Adult ; Aged ; Bile Acids and Salts/*metabolism ; Clostridium Infections/*therapy ; Fatty Acids, Volatile/*metabolism ; *Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome ; Humans ; Longitudinal Studies ; Male ; Metabolomics ; Middle Aged ; RNA, Bacterial/genetics ; RNA, Ribosomal, 16S/genetics ; Secondary Prevention/*methods ; Sequence Analysis, DNA ; Young Adult ; }, abstract = {A significant proportion of individuals develop recurrent Clostridium difficile infection (CDI) following initial disease. Fecal microbiota transplantation (FMT), a highly effective treatment method for recurrent CDI, has been demonstrated to induce microbiota recovery. One of the proposed functions associated with restoration of colonization resistance against C. difficile has been recovery of bile acid metabolism. In this study, we aimed to assess recovery of short chain fatty acids (SCFAs) in addition to bile acids alongside microbial community structure in six patients with recurrent CDI following treatment with FMT over time. Using 16S rRNA gene-based sequencing, we observed marked similarity of the microbiota between recipients following FMT (n = 6, sampling up to 6 months post-FMT) and their respective donors. Sustained increases in the levels of the SCFAs butyrate, acetate, and propionate were observed post-FMT, and variable recovery over time was observed in the secondary bile acids deoxycholate and lithocholate. To correlate these changes with specific microbial taxa at an individual level, we applied a generalized estimating equation approach to model metabolite concentrations with the presence of specific members of the microbiota. Metabolites that increased following FMT were associated with bacteria classified within the Lachnospiraceae, Ruminococcaceae, and unclassified Clostridiales families. In contrast, members of these taxa were inversely associated with primary bile acids. The longitudinal aspect of this study allowed us to characterize individualized patterns of recovery, revealing variability between and within patients following FMT.}, }
@article {pmid29643839, year = {2018}, author = {Zhai, J and Kim, J and Knox, KS and Twigg, HL and Zhou, H and Zhou, JJ}, title = {Variance Component Selection With Applications to Microbiome Taxonomic Data.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {509}, pmid = {29643839}, issn = {1664-302X}, support = {P30 ES006694/ES/NIEHS NIH HHS/United States ; }, abstract = {High-throughput sequencing technology has enabled population-based studies of the role of the human microbiome in disease etiology and exposure response. Microbiome data are summarized as counts or composition of the bacterial taxa at different taxonomic levels. An important problem is to identify the bacterial taxa that are associated with a response. One method is to test the association of specific taxon with phenotypes in a linear mixed effect model, which incorporates phylogenetic information among bacterial communities. Another type of approaches consider all taxa in a joint model and achieves selection via penalization method, which ignores phylogenetic information. In this paper, we consider regression analysis by treating bacterial taxa at different level as multiple random effects. For each taxon, a kernel matrix is calculated based on distance measures in the phylogenetic tree and acts as one variance component in the joint model. Then taxonomic selection is achieved by the lasso (least absolute shrinkage and selection operator) penalty on variance components. Our method integrates biological information into the variable selection problem and greatly improves selection accuracies. Simulation studies demonstrate the superiority of our methods versus existing methods, for example, group-lasso. Finally, we apply our method to a longitudinal microbiome study of Human Immunodeficiency Virus (HIV) infected patients. We implement our method using the high performance computing language Julia. Software and detailed documentation are freely available at https://github.com/JingZhai63/VCselection.}, }
@article {pmid29641531, year = {2018}, author = {Fan, X and Peters, BA and Min, D and Ahn, J and Hayes, RB}, title = {Comparison of the oral microbiome in mouthwash and whole saliva samples.}, journal = {PloS one}, volume = {13}, number = {4}, pages = {e0194729}, pmid = {29641531}, issn = {1932-6203}, support = {R01 CA159036/CA/NCI NIH HHS/United States ; R01 CA164964/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Bacteria/*classification ; Cohort Studies ; DNA, Bacterial/analysis ; Healthy Volunteers ; Humans ; Microbiota/*genetics ; Middle Aged ; Mouth Mucosa/microbiology ; *Mouthwashes ; Phylogeny ; Prospective Studies ; RNA, Ribosomal, 16S/genetics ; Saliva/*microbiology ; Specimen Handling ; }, abstract = {Population-based epidemiologic studies can provide important insight regarding the role of the microbiome in human health and disease. Buccal cells samples using commercial mouthwash have been obtained in large prospective cohorts for the purpose of studying human genomic DNA. We aimed to better understand if these mouthwash samples are also a valid resource for the study of the oral microbiome. We collected one saliva sample and one Scope mouthwash sample from 10 healthy subjects. Bacterial 16S rRNA genes from both types of samples were amplified, sequenced, and assigned to bacterial taxa. We comprehensively compared these paired samples for bacterial community composition and individual taxonomic abundance. We found that mouthwash samples yielded similar amount of bacterial DNA as saliva samples (p from Student's t-test for paired samples = 0.92). Additionally, the paired samples had similar within sample diversity (p from = 0.33 for richness, and p = 0.51 for Shannon index), and clustered as pairs for diversity when analyzed by unsupervised hierarchical cluster analysis. No significant difference was found in the paired samples with respect to the taxonomic abundance of major bacterial phyla, Bacteroidetes, Firmicutes, Proteobacteria, Fusobacteria, and Actinobacteria (FDR adjusted q values from Wilcoxin signed-rank test = 0.15, 0.15, 0.87, 1.00 and 0.15, respectively), and all identified genera, including genus Streptococcus (q = 0.21), Prevotella (q = 0.25), Neisseria (q = 0.37), Veillonella (q = 0.73), Fusobacterium (q = 0.19), and Porphyromonas (q = 0.60). These results show that mouthwash samples perform similarly to saliva samples for analysis of the oral microbiome. Mouthwash samples collected originally for analysis of human DNA are also a resource suitable for human microbiome research.}, }
@article {pmid29641525, year = {2018}, author = {Weber, KS and Bridgewater, LC and Jensen, JL and Breakwell, DP and Nielsen, BL and Johnson, SM}, title = {Personal microbiome analysis improves student engagement and interest in Immunology, Molecular Biology, and Genomics undergraduate courses.}, journal = {PloS one}, volume = {13}, number = {4}, pages = {e0193696}, pmid = {29641525}, issn = {1932-6203}, mesh = {Allergy and Immunology/*education ; *Attitude ; Genomics/*education ; Humans ; *Microbiota ; Molecular Biology/*education ; *Students ; Universities ; }, abstract = {A critical area of emphasis for science educators is the identification of effective means of teaching and engaging undergraduate students. Personal microbiome analysis is a means of identifying the microbial communities found on or in our body. We hypothesized the use of personal microbiome analysis in the classroom could improve science education by making courses more applied and engaging for undergraduate students. We determined to test this prediction in three Brigham Young University undergraduate courses: Immunology, Advanced Molecular Biology Laboratory, and Genomics. These three courses have a two-week microbiome unit and students during the 2016 semester students could submit their own personal microbiome kit or use the demo data, whereas during the 2017 semester students were given access to microbiome data from an anonymous individual. The students were surveyed before, during, and after the human microbiome unit to determine whether analyzing their own personal microbiome data, compared to analyzing demo microbiome data, impacted student engagement and interest. We found that personal microbiome analysis significantly enhanced the engagement and interest of students while completing microbiome assignments, the self-reported time students spent researching the microbiome during the two week microbiome unit, and the attitudes of students regarding the course overall. Thus, we found that integrating personal microbiome analysis in the classroom was a powerful means of improving student engagement and interest in undergraduate science courses.}, }
@article {pmid29636512, year = {2018}, author = {Pechal, JL and Schmidt, CJ and Jordan, HR and Benbow, ME}, title = {A large-scale survey of the postmortem human microbiome, and its potential to provide insight into the living health condition.}, journal = {Scientific reports}, volume = {8}, number = {1}, pages = {5724}, pmid = {29636512}, issn = {2045-2322}, abstract = {The microbiome plays many roles in human health, often through the exclusive lens of clinical interest. The inevitable end point for all living hosts, death, has its own altered microbiome configurations. However, little is understood about the ecology and changes of microbial communities after death, or their potential utility for understanding the health condition of the recently living. Here we reveal distinct postmortem microbiomes of human hosts from a large-scale survey of death cases representing a predominantly urban population, and demonstrated these microbiomes reflected antemortem health conditions within 24-48 hours of death. Our results characterized microbial community structure and predicted function from 188 cases representing a cross-section of an industrial-urban population. We found strong niche differentiation of anatomic habitat and microbial community turnover based on topographical distribution. Microbial community stability was documented up to two days after death. Additionally, we observed a positive relationship between cell motility and time since host death. Interestingly, we discovered evidence that microbial biodiversity is a predictor of antemortem host health condition (e.g., heart disease). These findings improve the understanding of postmortem host microbiota dynamics, and provide a robust dataset to test the postmortem microbiome as a tool for assessing health conditions in living populations.}, }
@article {pmid29636439, year = {2018}, author = {Brown, CT and Xiong, W and Olm, MR and Thomas, BC and Baker, R and Firek, B and Morowitz, MJ and Hettich, RL and Banfield, JF}, title = {Hospitalized Premature Infants Are Colonized by Related Bacterial Strains with Distinct Proteomic Profiles.}, journal = {mBio}, volume = {9}, number = {2}, pages = {}, pmid = {29636439}, issn = {2150-7511}, support = {R01 AI092531/AI/NIAID NIH HHS/United States ; R01 GM103600/GM/NIGMS NIH HHS/United States ; }, mesh = {Bacteria/*chemistry/classification/genetics ; Biota ; Enterocolitis, Necrotizing/microbiology/pathology ; Feces/microbiology ; Female ; *Gastrointestinal Microbiome ; *Hospitalization ; Humans ; Infant, Newborn ; *Infant, Premature ; Male ; Metagenome ; Metagenomics ; *Microbiota ; Proteome/*analysis ; Proteomics ; }, abstract = {During the first weeks of life, microbial colonization of the gut impacts human immune system maturation and other developmental processes. In premature infants, aberrant colonization has been implicated in the onset of necrotizing enterocolitis (NEC), a life-threatening intestinal disease. To study the premature infant gut colonization process, genome-resolved metagenomics was conducted on 343 fecal samples collected during the first 3 months of life from 35 premature infants housed in a neonatal intensive care unit, 14 of whom developed NEC, and metaproteomic measurements were made on 87 samples. Microbial community composition and proteomic profiles remained relatively stable on the time scale of a week, but the proteome was more variable. Although genetically similar organisms colonized many infants, most infants were colonized by distinct strains with metabolic profiles that could be distinguished using metaproteomics. Microbiome composition correlated with infant, antibiotics administration, and NEC diagnosis. Communities were found to cluster into seven primary types, and community type switched within infants, sometimes multiple times. Interestingly, some communities sampled from the same infant at subsequent time points clustered with those of other infants. In some cases, switches preceded onset of NEC; however, no species or community type could account for NEC across the majority of infants. In addition to a correlation of protein abundances with organism replication rates, we found that organism proteomes correlated with overall community composition. Thus, this genome-resolved proteomics study demonstrated that the contributions of individual organisms to microbiome development depend on microbial community context.IMPORTANCE Humans are colonized by microbes at birth, a process that is important to health and development. However, much remains to be known about the fine-scale microbial dynamics that occur during the colonization period. We conducted a genome-resolved study of microbial community composition, replication rates, and proteomes during the first 3 months of life of both healthy and sick premature infants. Infants were found to be colonized by similar microbes, but each underwent a distinct colonization trajectory. Interestingly, related microbes colonizing different infants were found to have distinct proteomes, indicating that microbiome function is not only driven by which organisms are present, but also largely depends on microbial responses to the unique set of physiological conditions in the infant gut.}, }
@article {pmid29634682, year = {2018}, author = {Gilbert, JA and Blaser, MJ and Caporaso, JG and Jansson, JK and Lynch, SV and Knight, R}, title = {Current understanding of the human microbiome.}, journal = {Nature medicine}, volume = {24}, number = {4}, pages = {392-400}, pmid = {29634682}, issn = {1546-170X}, support = {U54 CA143925/CA/NCI NIH HHS/United States ; }, mesh = {Biomarkers/metabolism ; Disease ; Humans ; Life Style ; *Microbiota ; Precision Medicine ; Translational Medical Research ; }, abstract = {Our understanding of the link between the human microbiome and disease, including obesity, inflammatory bowel disease, arthritis and autism, is rapidly expanding. Improvements in the throughput and accuracy of DNA sequencing of the genomes of microbial communities that are associated with human samples, complemented by analysis of transcriptomes, proteomes, metabolomes and immunomes and by mechanistic experiments in model systems, have vastly improved our ability to understand the structure and function of the microbiome in both diseased and healthy states. However, many challenges remain. In this review, we focus on studies in humans to describe these challenges and propose strategies that leverage existing knowledge to move rapidly from correlation to causation and ultimately to translation into therapies.}, }
@article {pmid29633119, year = {2018}, author = {Skowron, KB and Shogan, BD and Rubin, DT and Hyman, NH}, title = {The New Frontier: the Intestinal Microbiome and Surgery.}, journal = {Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract}, volume = {22}, number = {7}, pages = {1277-1285}, pmid = {29633119}, issn = {1873-4626}, mesh = {Anastomotic Leak/*microbiology ; Digestive System Surgical Procedures/*adverse effects ; *Gastrointestinal Microbiome ; Humans ; Intestinal Mucosa/microbiology ; Microbiota/*physiology ; }, abstract = {The microbiome exerts a remarkable effect on human physiology. The study of the human-microbiome relationship is a burgeoning field with great potential to improve our understanding of health and disease. In this review, we address common surgical problems influenced by the human microbiome and explore what is thus far known about this relationship. These include inflammatory bowel disease, colorectal neoplasms, and diverticular disease. We will also discuss the effect of the microbiome on surgical complications, specifically anastomotic leak. We hope that further research in this field will enlighten our management of these and other surgical problems.}, }
@article {pmid29629420, year = {2018}, author = {Langille, MGI}, title = {Exploring Linkages between Taxonomic and Functional Profiles of the Human Microbiome.}, journal = {mSystems}, volume = {3}, number = {2}, pages = {}, pmid = {29629420}, issn = {2379-5077}, abstract = {Microbiome studies typically focus on characterizing the taxonomic and functional profiles of the microbes within a community. Functional profiling is generally thought to be superior to taxonomic profiling for investigating human-microbe interactions, but there are several limitations and challenges to existing approaches. This Perspective discusses the current sequencing and bioinformatic methods for producing taxonomic and functional profiles, recent studies utilizing and comparing these technologies, and the existing challenges and limitations of these data. In addition, functional versus taxonomic conservation across the population is questioned, while future research that focuses on investigating the taxonomic diversity of microbial functions is proposed.}, }
@article {pmid29629416, year = {2018}, author = {Lieberman, TD}, title = {Seven Billion Microcosms: Evolution within Human Microbiomes.}, journal = {mSystems}, volume = {3}, number = {2}, pages = {}, pmid = {29629416}, issn = {2379-5077}, abstract = {Rational microbiome-based therapies may one day treat a wide range of diseases and promote wellness. Yet, we are still limited in our abilities to employ such therapies and to predict which bacterial strains have the potential to stably colonize a person. The Lieberman laboratory is working to close this knowledge gap and to develop an understanding of how individual species and strains behave in the human microbiome, including with regard to their niche ranges, survival strategies, and the degree to which they adapt to individual people. We employ system-level approaches, with a particular emphasis on using de novo mutations and evolutionary inference to reconstruct the history of bacterial lineages within individuals.}, }
@article {pmid29629415, year = {2018}, author = {David, LA}, title = {Toward Personalized Control of Human Gut Bacterial Communities.}, journal = {mSystems}, volume = {3}, number = {2}, pages = {}, pmid = {29629415}, issn = {2379-5077}, support = {R01 DK116187/DK/NIDDK NIH HHS/United States ; R24 DK110492/DK/NIDDK NIH HHS/United States ; }, abstract = {A key challenge in microbiology will be developing tools for manipulating human gut bacterial communities. Our ability to predict and control the dynamics of these communities is now in its infancy. To manage human gut microbiota, I am developing methods in three research domains. First, I am refining in vitro tools to experimentally study gut microbes at high throughput and in controlled settings. Second, I am adapting &quot;big data&quot; techniques to overcome statistical challenges confronting microbiota modeling. Third, I am testing study designs that can streamline human testing of microbiota manipulations. Assembling these methods creates new challenges, including training scientists who can work across disciplines such as engineering, ecology, and medicine. Nevertheless, I envision that overcoming these obstacles will enable my group to construct platforms that can personalize microbiota treatments, particularly ones based on diet. More broadly, I anticipate that such platforms will have applications across fields such as agriculture, biotechnology, and environmental management.}, }
@article {pmid29627609, year = {2018}, author = {Lu, W and Negi, SS and Schein, CH and Maleki, SJ and Hurlburt, BK and Braun, W}, title = {Distinguishing allergens from non-allergenic homologues using Physical-Chemical Property (PCP) motifs.}, journal = {Molecular immunology}, volume = {99}, number = {}, pages = {1-8}, pmid = {29627609}, issn = {1872-9142}, support = {R21 AI109090/AI/NIAID NIH HHS/United States ; }, mesh = {Allergens/*chemistry/*immunology ; Cross Reactions/immunology ; Epitopes/chemistry/immunology ; Fruit/chemistry/immunology ; Humans ; Immunoglobulin E/chemistry/immunology ; Nuts/chemistry/immunology ; Plant Proteins/chemistry/immunology ; Pollen/chemistry/immunology ; Polysaccharide-Lyases/chemistry/immunology ; Profilins/chemistry/immunology ; }, abstract = {Quantitative guidelines to distinguish allergenic proteins from related, but non-allergenic ones are urgently needed for regulatory agencies, biotech companies and physicians. In a previous study, we found that allergenic proteins populate a relatively small number of protein families, as characterized by the Pfam database. However, these families also contain non-allergenic proteins, meaning that allergenic determinants must lie within more discrete regions of the sequence. Thus, new methods are needed to discriminate allergenic proteins within those families. Physical-Chemical Properties (PCP)-motifs specific for allergens within a Pfam class were determined for 17 highly populated protein domains. A novel scoring method based on PCP-motifs that characterize known allergenic proteins within these families was developed, and validated for those domains. The motif scores distinguished sequences of allergens from a large selection of 80,000 randomly selected non-allergenic sequences. The motif scores for the birch pollen allergen (Bet v 1) family, which also contains related fruit and nut allergens, correlated better than global sequence similarities with clinically observed cross-reactivities among those allergens. Further, we demonstrated that the average scores of allergen specific motifs for allergenic profilins are significantly different from the scores of non-allergenic profilins. Several of the selective motifs coincide with experimentally determined IgE epitopes of allergenic profilins. The motifs also discriminated allergenic pectate lyases, including Jun a 1 from mountain cedar pollen, from similar proteins in the human microbiome, which can be assumed to be non-allergens. The latter lacked key motifs characteristic of the known allergens, some of which correlate with known IgE binding sites.}, }
@article {pmid29623445, year = {2018}, author = {Ho, HE and Bunyavanich, S}, title = {Role of the Microbiome in Food Allergy.}, journal = {Current allergy and asthma reports}, volume = {18}, number = {4}, pages = {27}, pmid = {29623445}, issn = {1534-6315}, mesh = {Animals ; Child ; Dysbiosis/*immunology ; Food Hypersensitivity/*microbiology ; Humans ; Immune System/physiology ; Immune Tolerance/*immunology ; Microbiota/*physiology ; Probiotics ; }, abstract = {PURPOSE OF REVIEW: Resident microbial communities likely modify risk for allergic disorders, including food allergy. We review epidemiologic studies linking microbial exposures to food allergy risk and discuss the mechanisms by which the microbiome may modulate oral tolerance. We additionally address ongoing translational efforts in human microbiome studies.<br><br>RECENT FINDINGS: Epidemiologic studies and murine models support that altered microbial exposures and colonization in early life modify food allergy risk. Differential microbiota confer protection or susceptibility to food allergy by modulating the regulatory tone of the mucosal immune system. Recent efforts are focused on the identification of bacterial strains necessary for oral tolerance in human and microbial-based clinical trials. Early childhood appears to be critical for the colonization of a diverse microbiota necessary for the induction and maintenance of oral tolerance. Identification and functional evaluation of protective commensal microbes will inform strategies for the prevention and treatment of food allergy.}, }
@article {pmid29619642, year = {2018}, author = {Srinivasan, VB and Angrasan, M and Chandel, N and Rajamohan, G}, title = {Genome sequence and comparative analysis of Bacillus cereus BC04, reveals genetic diversity and alterations for antimicrobial resistance.}, journal = {Functional &amp; integrative genomics}, volume = {18}, number = {4}, pages = {477-487}, pmid = {29619642}, issn = {1438-7948}, support = {BT/HRD/NBA/34/01/2012//Department of Biotechnology , Ministry of Science and Technology/ ; BT/01/IYBA/2009//Department of Biotechnology , Ministry of Science and Technology/ ; BSC0119H//Council of Scientific and Industrial Research/ ; SB/YS/LS-177/2014//Science and Engineering Research Board/ ; }, mesh = {Bacillus cereus/classification/drug effects/*genetics ; Drug Resistance, Bacterial/*genetics ; *Genome, Bacterial ; Molecular Sequence Annotation ; Phylogeny ; *Polymorphism, Genetic ; }, abstract = {In this study, we delineated the genome sequence of a Bacillus cereus strain BC04 isolated from a stool sample in India. The draft genome is 5.1 Mb in size and consists of total 109 scaffolds, GC content is 35.2% with 5182 coding genes. The comparative analysis with other completely sequenced genomes highlights the unique presence of genomic islands, hemolysin, capsular synthetic protein, modifying enzymes accC7 and catA15, regulators of antibiotic resistance MarR and LysR with annotated functions related to virulence, stress response, and antimicrobial resistance. Overall, this study not only signifies the genetic diversity in gut isolate BC04 in particular, but also pinpoints the presence of unique genes possessed by B. cereus which can be pertinently exploited to design novel drugs and intervention strategies for the treatment of food borne diseases.}, }
@article {pmid29617920, year = {2018}, author = {Demmer, RT}, title = {Invited Commentary: The Microbiome and Population Health-Considerations for Enhancing Study Design and Data Analysis in Observational and Interventional Epidemiology.}, journal = {American journal of epidemiology}, volume = {187}, number = {6}, pages = {1291-1294}, pmid = {29617920}, issn = {1476-6256}, support = {R01 DK102932/DK/NIDDK NIH HHS/United States ; }, mesh = {Data Analysis ; Epidemiologic Studies ; Humans ; *Microbiota ; *Population Health ; Research Design ; }, abstract = {Measurement and characterization of the human microbiome in large population-based human studies has recently become a reality secondary to technological advances in high-throughput DNA sequencing. These advances bring new challenges and knowledge gaps for study planning, data analysis, and interpretation that are novel to large-scale epidemiologic studies. In this issue of the Journal, Sinha et al. (Am J Epidemiol. 2018;187(6):1282-1290) have provided data with which to inform statistical power and sample size requirements for microbiome studies in population-based settings. This work serves as a helpful starting point for study planning while also serving as a springboard for discussion regarding additional considerations for improving microbiome research. This commentary emphasizes the importance of selecting microbiome metrics appropriate for the biological hypothesis under investigation, as well as the need for new analytical tools that can better capitalize on the unique yet rich information contained in microbiome data sets.}, }
@article {pmid29608646, year = {2018}, author = {Sinha, R and Goedert, JJ and Vogtmann, E and Hua, X and Porras, C and Hayes, R and Safaeian, M and Yu, G and Sampson, J and Ahn, J and Shi, J}, title = {Quantification of Human Microbiome Stability Over 6 Months: Implications for Epidemiologic Studies.}, journal = {American journal of epidemiology}, volume = {187}, number = {6}, pages = {1282-1290}, pmid = {29608646}, issn = {1476-6256}, support = {R03 CA159414/CA/NCI NIH HHS/United States ; }, mesh = {Feces/microbiology ; Female ; *Gastrointestinal Microbiome ; Humans ; Male ; Time Factors ; }, abstract = {Temporal variation in microbiome measurements can reduce statistical power in research studies. Quantification of this variation is essential for designing studies of chronic disease. We analyzed 16S ribosomal RNA profiles in paired biological specimens separated by 6 months from 3 studies conducted during 1985-2013 (a National Cancer Institute colorectal cancer study, a Costa Rica study, and the Human Microbiome Project). We evaluated temporal stability by calculating intraclass correlation coefficients (ICCs). Sample sizes needed in order to detect microbiome differences between equal numbers of cases and controls for a nested case-control design were calculated on the basis of estimated ICCs. Across body sites, 12 phylum-level ICCs were greater than 0.5. Similarly, 11 alpha-diversity ICCs were greater than 0.5. Fecal beta-diversity estimates had ICCs over 0.5. For a single collection with most microbiome metrics, detecting an odds ratio of 2.0 would require 300-500 cases when matching 1 case to 1 control at P = 0.05. Use of 2 or 3 sequential specimens reduces the number of required subjects by 40%-50% for low-ICC metrics. Relative abundances of major phyla and alpha-diversity metrics have low temporal stability. Thus, detecting associations of moderate effect size with these metrics will require large sample sizes. Because beta diversity for feces is reasonably stable over time, smaller sample sizes can detect associations with community composition. Sequential prediagnostic specimens from thousands of prospectively ascertained cases are required to detect modest disease associations with particular microbiome metrics.}, }
@article {pmid29596364, year = {2018}, author = {Vallone, C and Rigon, G and Gulia, C and Baffa, A and Votino, R and Morosetti, G and Zaami, S and Briganti, V and Catania, F and Gaffi, M and Nucciotti, R and Costantini, FM and Piergentili, R and Putignani, L and Signore, F}, title = {Non-Coding RNAs and Endometrial Cancer.}, journal = {Genes}, volume = {9}, number = {4}, pages = {}, pmid = {29596364}, issn = {2073-4425}, abstract = {Non-coding RNAs (ncRNAs) are involved in the regulation of cell metabolism and neoplastic transformation. Recent studies have tried to clarify the significance of these information carriers in the genesis and progression of various cancers and their use as biomarkers for the disease; possible targets for the inhibition of growth and invasion by the neoplastic cells have been suggested. The significance of ncRNAs in lung cancer, bladder cancer, kidney cancer, and melanoma has been amply investigated with important results. Recently, the role of long non-coding RNAs (lncRNAs) has also been included in cancer studies. Studies on the relation between endometrial cancer (EC) and ncRNAs, such as small ncRNAs or micro RNAs (miRNAs), transfer RNAs (tRNAs), ribosomal RNAs (rRNAs), antisense RNAs (asRNAs), small nuclear RNAs (snRNAs), Piwi-interacting RNAs (piRNAs), small nucleolar RNAs (snoRNAs), competing endogenous RNAs (ceRNAs), lncRNAs, and long intergenic ncRNAs (lincRNAs) have been published. The recent literature produced in the last three years was extracted from PubMed by two independent readers, which was then selected for the possible relation between ncRNAs, oncogenesis in general, and EC in particular.}, }
@article {pmid29570689, year = {2018}, author = {Cinelli, G and Fabrizi, M and Ravà, L and Signore, F and Vernocchi, P and Semeraro, M and Vallone, C and Lanciotti, R and Ciofi Degli Atti, M and Manco, M}, title = {Association between Maternal and Foetal Erythrocyte Fatty Acid Profiles and Birth Weight.}, journal = {Nutrients}, volume = {10}, number = {4}, pages = {}, pmid = {29570689}, issn = {2072-6643}, mesh = {Adult ; *Birth Weight ; Erythrocytes/*metabolism ; Fatty Acids/adverse effects/*blood ; Fatty Acids, Omega-6/blood ; Female ; Fetal Blood/*metabolism ; Gestational Age ; Humans ; Infant, Newborn ; *Infant, Small for Gestational Age ; Maternal Nutritional Physiological Phenomena ; Nutritional Status ; Pregnancy ; Risk Factors ; }, abstract = {Regular foetal development is crucial for assuring good health status in the offspring. The quality and quantity of maternal dietary fatty acids (FAs) can affect growth. The study aimed to: (1) investigate the association of maternal/foetal lipid profiles with birth weight (BW); and (2) compare these profiles in small, appropriate, and large for gestational age (SGA, AGA, and LGA) infants. FAs were measured in erythrocyte membranes using gas chromatography analysis in 607 mother-infant pairs (316 males, 52.1%). In the quantile regression, a significant association between BW and levels of maternal linoleic acid (LA; C18:2, n-6; coefficient: 18.66; p = 0.010), arachidonic acid (AA; C20:4, n-6; coefficient: 11.35; p = 0.007), docosahexaenoic acid (DHA; C22:6, n-3; coefficient: 29.73; p = 0.007), polyunsaturated FAs (coefficient: 8.55; p = 0.001), foetal DHA (coefficient: -22.82; p = 0.037), and saturated FAs (coefficient: -65.41; p = 0.002) was found. Myristic (C14:0) and pentadecanoic acids (C15:0), both maternal (p = 0.000; p = 0.017) and foetal (p = 0.009; p = 0.002), and maternal erucic acid (C22:1, n-9; p = 0.026) were found at higher levels in SGA infants as compared to AGA ones. Conversely, maternal LA, AA, and omega 6 FAs levels were higher in AGA infants (p = 0.037; p = 0.003; p = 0.026, respectively). Maternal and foetal polyunsaturated and omega 6 FAs levels are positively related to BW, while a lipid profile rich in saturated FAs and erucic acid may influence the risk of SGA.}, }
@article {pmid29568746, year = {2018}, author = {Wu, H and Cai, L and Li, D and Wang, X and Zhao, S and Zou, F and Zhou, K}, title = {Metagenomics Biomarkers Selected for Prediction of Three Different Diseases in Chinese Population.}, journal = {BioMed research international}, volume = {2018}, number = {}, pages = {2936257}, pmid = {29568746}, issn = {2314-6141}, mesh = {Algorithms ; Arthritis, Rheumatoid/*microbiology ; Asian Continental Ancestry Group/*genetics ; Biomarkers/*metabolism ; Diabetes Mellitus, Type 2/*microbiology ; Dysbiosis/genetics ; Female ; Humans ; Liver Cirrhosis/*microbiology ; Male ; Metagenome/*genetics ; Metagenomics/methods ; Microbiota/*genetics ; Middle Aged ; ROC Curve ; }, abstract = {The dysbiosis of human mi