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Bibliography on: Human Microbiome

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ESP: PubMed Auto Bibliography 27 Nov 2020 at 01:50 Created: 

Human Microbiome

The human microbiome is the set of all microbes that live on or in humans. Together, a human body and its associated microbiomes constitute a human holobiont. Although a human holobiont is mostly mammal by weight, by cell count it is mostly microbial. The number of microbial genes in the associated microbiomes far outnumber the number of human genes in the human genome. Just as humans (and other multicellular eukaryotes) evolved in the constant presence of gravity, so they also evolved in the constant presence of microbes. Consequently, nearly every aspect of human biology has evolved to deal with, and to take advantage of, the existence of associated microbiota. In some cases, the absence of a "normal microbiome" can cause disease, which can be treated by the transplant of a correct microbiome from a healthy donor. For example, fecal transplants are an effective treatment for chronic diarrhea from over abundant Clostridium difficile bacteria in the gut.

Created with PubMed® Query: "human microbiome" NOT pmcbook NOT ispreviousversion

Citations The Papers (from PubMed®)


RevDate: 2020-11-25

Montecchiani V, V Fanos (2020)

Human microbiome and allergy.

Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology, 31 Suppl 26:5-7.

Human microbiome contributes to critical functions that impact health and disease. It influences the development of the immune system, and the pathogenesis of immunological disorders included allergy. While it is easy to understand how airway microbiome, influencing local inflammation and immune activity, could contribute to shaping asthma phenotype, it is not so obvious to understand the influence by the gut microbiome, but there is growing evidence about it. The increase of allergic disorders in western countries led to investigate the role environment is playing and how it may change our microbiome and immune system, with the hope of finding new preventive approaches for allergy.

RevDate: 2020-11-25

Hasan A, Hasan LK, Schnabl B, et al (2020)

Microbiome of the Aerodigestive Tract in Health and Esophageal Disease.

Digestive diseases and sciences pii:10.1007/s10620-020-06720-6 [Epub ahead of print].

The diverse human gut microbiome is comprised of approximately 40 trillion microorganisms representing up to 1000 different bacterial species. The human microbiome plays a critical role in gut epithelial health and disease susceptibility. While the interaction between gut microbiome and gastrointestinal pathology is increasingly understood, less is known about the interaction between the microbiome and the aerodigestive tract. This review of the microbiome of the aerodigestive tract in health, and alterations in microbiome across esophageal pathologies highlights important findings and areas for future research. First, microbiome profiles are distinct along the aerodigestive tract, spanning the oral cavity to the stomach. In patients with reflux-related disease such as gastro-esophageal reflux disease, Barrett's esophagus, and esophageal adenocarcinoma, investigators have observed an overall increase in gram negative bacteria in the esophageal microbiome compared to healthy individuals. However, whether differences in microbiome promote disease development, or if these shifts are a consequence of disease remains unknown. Interestingly, use of proton pump inhibitor therapy is also associated with shifts in the microbiome, with distinct shifts and patterns along the aerodigestive tract. The relationship between the human gut microbiome and esophageal pathology is a ripe area for investigation, and further understanding of these pathways may promote development of novel targets in prevention and therapy for esophageal diseases.

RevDate: 2020-11-24

Lyles JK, M Oli (2020)

The Student-Centered Classroom: The New Gut Feeling.

FEMS microbiology letters pii:6000213 [Epub ahead of print].

A student-centered, interactive course-based undergraduate research experience (CURE) was implemented in a microbiology course in order to provide an authentic research experience and to stimulate student interest and improve understanding of fermentation, probiotics, the human microbiome, and related topics. Students were immersed in the scientific process as they used fundamental techniques to investigate the probiotic composition of a fermented milk beverage, kefir-an unknown question with no predetermined outcomes. In order to assess the benefits and effect of this learning experience on the students, pre- and post-study surveys were administered using Qualtrics. Post-study, 93% of participants agreed that fermented foods are beneficial to human health (compared to 52% pre-study), and notably, 100% of participants indicated that they plan to apply this material in both their personal and professional lives and would suggest consuming probiotics or fermented products to alleviate gastrointestinal issues. As evidenced by demographic data, this CURE is suitable for implementation at both large and small institutions with diverse student populations. Collectively, these data indicate that this collaborative, discovery-based learning experience is a powerful educational tool, encouraging students to make real-life connections between microbiology, medicine, and their own health.

RevDate: 2020-11-24

Vernocchi P, Gili T, Conte F, et al (2020)

Network Analysis of Gut Microbiome and Metabolome to Discover Microbiota-Linked Biomarkers in Patients Affected by Non-Small Cell Lung Cancer.

International journal of molecular sciences, 21(22): pii:ijms21228730.

Several studies in recent times have linked gut microbiome (GM) diversity to the pathogenesis of cancer and its role in disease progression through immune response, inflammation and metabolism modulation. This study focused on the use of network analysis and weighted gene co-expression network analysis (WGCNA) to identify the biological interaction between the gut ecosystem and its metabolites that could impact the immunotherapy response in non-small cell lung cancer (NSCLC) patients undergoing second-line treatment with anti-PD1. Metabolomic data were merged with operational taxonomic units (OTUs) from 16S RNA-targeted metagenomics and classified by chemometric models. The traits considered for the analyses were: (i) condition: disease or control (CTRLs), and (ii) treatment: responder (R) or non-responder (NR). Network analysis indicated that indole and its derivatives, aldehydes and alcohols could play a signaling role in GM functionality. WGCNA generated, instead, strong correlations between short-chain fatty acids (SCFAs) and a healthy GM. Furthermore, commensal bacteria such as Akkermansia muciniphila, Rikenellaceae, Bacteroides, Peptostreptococcaceae, Mogibacteriaceae and Clostridiaceae were found to be more abundant in CTRLs than in NSCLC patients. Our preliminary study demonstrates that the discovery of microbiota-linked biomarkers could provide an indication on the road towards personalized management of NSCLC patients.

RevDate: 2020-11-23

Araujo DV, Watson GA, Oliva M, et al (2020)

Bugs as drugs: The role of microbiome in cancer focusing on immunotherapeutics.

Cancer treatment reviews, 92:102125 pii:S0305-7372(20)30163-8 [Epub ahead of print].

The human microbiome comprising microorganisms, their collective genomes and metabolic products has gained tremendous research interest in oncology, as multiple cohorts and case studies have demonstrated discernible interpatient differences in this ecosystem based on clinical variables including disease type, stage, diet, antibiotic usage, cancer treatments, therapeutic responses and toxicities. The modulation of the gut microbiome is the subject of many ongoing preclinical and clinical investigations, through the manipulation of diet, as well as the use of prebiotics, probiotics, specific antibiotics, fecal microbial transplantation, microbial consortia and stool substitutes. Standardization and quality control are needed to maximize the information being generated in this growing field, ranging from technical assays to measure microbiome composition, to methodological aspects in the analysis and reporting of results. Proof-of-mechanism and proof-of-concept clinical trials with appropriate controls are needed to confirm or refute the feasibility, safety and ultimately the clinical utility of human microbiome modulation in cancer patients.

RevDate: 2020-11-23

McKenzie ND, Hong H, Ahmad S, et al (2020)

The gut microbiome and cancer immunotherapeutics: A review of emerging data and implications for future gynecologic cancer research.

Critical reviews in oncology/hematology, 157:103165 pii:S1040-8428(20)30301-2 [Epub ahead of print].

Investigation of the gynecologic tract microbial milieu has revealed potential new biomarkers. Simultaneously, immunotherapeutics are establishing their place in the treatment of gynecologic malignancies. The interplay between the microbiome, the tumor micro-environment and response to therapy is a burgeoning area of interest. There is evidence to support that microbes, through their genetic make-up, gene products, and metabolites affect human physiology, metabolism, immunity, disease susceptibility, response to pharmacotherapy, and the severity of disease-related side effects. Specifically, the richness and diversity of the gut microbiome appears to affect carcinogenesis, response to immunotherapy, and modulate severity of immune-mediated adverse effects. These effects have best been described in other tumor types and these have shown compelling results. This review summarizes the current understanding and scope of the interplay between the human microbiome, host factors, cancer, and response to treatments. These findings support further exploring whether these associations exist for gynecologic malignancies.

RevDate: 2020-11-23

Teles F, Wang Y, Hajishengallis G, et al (2020)

Impact of systemic factors in shaping the periodontal microbiome.

Periodontology 2000 [Epub ahead of print].

Since 2010, next-generation sequencing platforms have laid the foundation to an exciting phase of discovery in oral microbiology as it relates to oral and systemic health and disease. Next-generation sequencing has allowed large-scale oral microbial surveys, based on informative marker genes, such as 16S ribosomal RNA, community gene inventories (metagenomics), and functional analyses (metatranscriptomics), to be undertaken. More specifically, the availability of next-generation sequencing has also paved the way for studying, in greater depth and breadth, the effect of systemic factors on the periodontal microbiome. It was natural to investigate systemic diseases, such as diabetes, in such studies, along with systemic conditions or states, , pregnancy, menopause, stress, rheumatoid arthritis, and systemic lupus erythematosus. In addition, in recent years, the relevance of systemic "variables" (ie, factors that are not necessarily diseases or conditions, but may modulate the periodontal microbiome) has been explored in detail. These include ethnicity and genetics. In the present manuscript, we describe and elaborate on the new and confirmatory findings unveiled by next-generation sequencing as it pertains to systemic factors that may shape the periodontal microbiome. We also explore the systemic and mechanistic basis for such modulation and highlight the importance of those relationships in the management and treatment of patients.

RevDate: 2020-11-23

Duran-Pinedo AE (2020)

Metatranscriptomic analyses of the oral microbiome.

Periodontology 2000 [Epub ahead of print].

Although the composition of the oral human microbiome is now well studied, regulation of genes within oral microbial communities remains mostly uncharacterized. Current concepts of periodontal disease and caries highlight the importance of oral biofilms and their role as etiological agents of those diseases. Currently, there is increased interest in exploring and characterizing changes in the composition and gene-expression profiles of oral microbial communities. These efforts aim to identify changes in functional activities that could explain the transition from health to disease and the reason for the chronicity of those infections. It is now clear that the functions of distinct species within the subgingival microbiota are intimately intertwined with the rest of the microbial community. This point highlights the relevance of examining the expression profile of specific species within the subgingival microbiota in the case of periodontal disease or caries lesions, in the context of the other members of the biofilm in vivo. Metatranscriptomic analysis of the oral community is the starting point for identifying environmental signals that modulate the shift in metabolism of the community from commensal to dysbiotic. These studies give a snapshot of the expression patterns of microbial communities and also allow us to determine triggers to diseases. For example, in the case of caries, studies have unveiled a potential new pathway of sugar metabolism, namely the use of sorbitol as an additional source of carbon by Streptococcus mutans; and in the case of periodontal disease, high levels of extracellular potassium could be a signal of disease. Longitudinal studies are needed to identify the real markers of the initial stages of caries and periodontal disease. More information on the gene-expression profiles of the host, along with the patterns from the microbiome, will lead to a clearer understanding of the modulation of health and disease. This review presents a summary of these initial studies, which have opened the door to a new understanding of the dynamics of the oral community during the dysbiotic process in the oral cavity.

RevDate: 2020-11-22

Kasmanas JC, Bartholomäus A, Corrêa FB, et al (2020)

HumanMetagenomeDB: a public repository of curated and standardized metadata for human metagenomes.

Nucleic acids research pii:5998395 [Epub ahead of print].

Metagenomics became a standard strategy to comprehend the functional potential of microbial communities, including the human microbiome. Currently, the number of metagenomes in public repositories is increasing exponentially. The Sequence Read Archive (SRA) and the MG-RAST are the two main repositories for metagenomic data. These databases allow scientists to reanalyze samples and explore new hypotheses. However, mining samples from them can be a limiting factor, since the metadata available in these repositories is often misannotated, misleading, and decentralized, creating an overly complex environment for sample reanalysis. The main goal of the HumanMetagenomeDB is to simplify the identification and use of public human metagenomes of interest. HumanMetagenomeDB version 1.0 contains metadata of 69 822 metagenomes. We standardized 203 attributes, based on standardized ontologies, describing host characteristics (e.g. sex, age and body mass index), diagnosis information (e.g. cancer, Crohn's disease and Parkinson), location (e.g. country, longitude and latitude), sampling site (e.g. gut, lung and skin) and sequencing attributes (e.g. sequencing platform, average length and sequence quality). Further, HumanMetagenomeDB version 1.0 metagenomes encompass 58 countries, 9 main sample sites (i.e. body parts), 58 diagnoses and multiple ages, ranging from just born to 91 years old. The HumanMetagenomeDB is publicly available at

RevDate: 2020-11-20

Münch PC, Franzosa EA, Stecher B, et al (2020)

Identification of Natural CRISPR Systems and Targets in the Human Microbiome.

Cell host & microbe pii:S1931-3128(20)30573-4 [Epub ahead of print].

Many bacteria resist invasive DNA by incorporating sequences into CRISPR loci, which enable sequence-specific degradation. CRISPR systems have been well studied from isolate genomes, but culture-independent metagenomics provide a new window into their diversity. We profiled CRISPR loci and cas genes in the body-wide human microbiome using 2,355 metagenomes, yielding functional and taxonomic profiles for 2.9 million spacers by aligning the spacer content to each sample's metagenome and corresponding gene families. Spacer and repeat profiles agree qualitatively with those from isolate genomes but expand their diversity by approximately 13-fold, with the highest spacer load present in the oral microbiome. The taxonomy of spacer sequences parallels that of their source community, with functional targets enriched for viral elements. When coupled with cas gene systems, CRISPR-Cas subtypes are highly site and taxon specific. Our analysis provides a comprehensive collection of natural CRISPR-cas loci and targets in the human microbiome.

RevDate: 2020-11-19

Kim SA, Kang N, T Park (2020)

Hierarchical structured Component Analysis for Microbiome Data Using Taxonomy Assignments.

IEEE/ACM transactions on computational biology and bioinformatics, PP: [Epub ahead of print].

The advent of high-throughput sequencing technology has enabled us to study the associations between human microbiome and diseases. The DNA sequences of microbiome samples are clustered as operational taxonomic units (OTUs) according to their similarity. The OTU table is used to measure correlations between OTUs and disease status and find key microbes for prediction of the disease status. Various statistical methods have been proposed for such microbiome data analysis. However, none of these methods reflects the hierarchy of taxonomy information. Here, we propose a hierarchical structural component model for microbiome data (HisCoM-microb) using taxonomy information as well as OTU table data. The proposed HisCoM-microb consists of two layers: one for OTUs and the other for taxa at the higher taxonomy level. Then we calculate simultaneously coefficient estimates of OTUs and taxa of the two layers inserted in the hierarchical model. Through this analysis, we can infer the association between taxa or OTUs and disease status, considering the impact of taxonomic structure on disease status. Both simulation study and real microbiome data analysis show that HisCoM-microb can successfully reveal the relations between each taxon and disease status and identify the key OTUs of the disease at the same time.

RevDate: 2020-11-19

Hugerth LW, Pereira M, Zha Y, et al (2020)

Assessment of In Vitro and In Silico Protocols for Sequence-Based Characterization of the Human Vaginal Microbiome.

mSphere, 5(6):.

The vaginal microbiome has been connected to a wide range of health outcomes. This has led to a thriving research environment but also to the use of conflicting methodologies to study its microbial composition. Here, we systematically assessed best practices for the sequencing-based characterization of the human vaginal microbiome. As far as 16S rRNA gene sequencing is concerned, the V1-V3 region performed best in silico, but limitations of current sequencing technologies meant that the V3-V4 region performed equally well. Both approaches presented very good agreement with qPCR quantification of key taxa, provided that an appropriate bioinformatic pipeline was used. Shotgun metagenomic sequencing presents an interesting alternative to 16S rRNA gene amplification and sequencing but requires deeper sequencing and more bioinformatic expertise and infrastructure. We assessed different tools for the removal of host reads and the taxonomic annotation of metagenomic reads, including a new, easy-to-build and -use reference database of vaginal taxa. This curated database performed as well as the best-performing previously published strategies. Despite the many advantages of shotgun sequencing, none of the shotgun approaches assessed here agreed with the qPCR data as well as the 16S rRNA gene sequencing.IMPORTANCE The vaginal microbiome has been connected to various aspects of host health, including susceptibility to sexually transmitted infections as well as gynecological cancers and pregnancy outcomes. This has led to a thriving research environment but also to conflicting available methodologies, including many studies that do not report their molecular biological and bioinformatic methods in sufficient detail to be considered reproducible. This can lead to conflicting messages and delay progress from descriptive to intervention studies. By systematically assessing best practices for the characterization of the human vaginal microbiome, this study will enable past studies to be assessed more critically and assist future studies in the selection of appropriate methods for their specific research questions.

RevDate: 2020-11-19

Tsai JC, Casteneda G, Lee A, et al (2020)

Identification and Characterization of the Intra-Articular Microbiome in the Osteoarthritic Knee.

International journal of molecular sciences, 21(22): pii:ijms21228618.

Osteoarthritis (OA) is the most common joint disorder in the United States, and the gut microbiome has recently emerged as a potential etiologic factor in OA development. Recent studies have shown that a microbiome is present at joint synovia. Therefore, we aimed to characterize the intra-articular microbiome within osteoarthritic synovia and to illustrate its role in OA disease progression. RNA-sequencing data from OA patient synovial tissue was aligned to a library of microbial reference genomes to identify microbial reads indicative of microbial abundance. Microbial abundance data of OA and normal samples was compared to identify differentially abundant microbes. We computationally explored the correlation of differentially abundant microbes to immunological gene signatures, immune signaling pathways, and immune cell infiltration. We found that microbes correlated to OA are related to dysregulation of two main functional pathways: increased inflammation-induced extracellular matrix remodeling and decreased cell signaling pathways crucial for joint and immune function. We also confirmed that the differentially abundant and biologically relevant microbes we had identified were not contaminants. Collectively, our findings contribute to the understanding of the human microbiome, well-known OA risk factors, and the role microbes play in OA pathogenesis. In conclusion, we present previously undiscovered microbes implicated in the OA disease progression that may be useful for future treatment purposes.

RevDate: 2020-11-18

Perttu L, Jonna J, Anna H, et al (2020)

Letter: faecal microbiota transplantation for irritable bowel syndrome-which improvements are required? Authors' reply.

Alimentary pharmacology & therapeutics, 52(11-12):1754-1755.

RevDate: 2020-11-19

Al KF, Denstedt JD, Daisley BA, et al (2020)

Ureteral Stent Microbiota Is Associated with Patient Comorbidities but Not Antibiotic Exposure.

Cell reports. Medicine, 1(6):100094.

Ureteral stents are commonly used to prevent urinary obstruction but can become colonized by bacteria and encrusted, leading to clinical complications. Despite recent discovery and characterization of the healthy urinary microbiota, stent-associated bacteria and their impact on encrustation are largely underexplored. We profile the microbiota of patients with typical short-term stents, as well as over 30 atypical cases (all with paired mid-stream urine) from 241 patients. Indwelling time, age, and various patient comorbidities correlate with alterations to the stent microbiota composition, whereas antibiotic exposure, urinary tract infection (UTI), and stent placement method do not. The stent microbiota most likely originates from adhesion of resident urinary microbes but subsequently diverges to a distinct, reproducible population, thereby negating the urine as a biomarker for stent encrustation or microbiota. Urological practice should reconsider standalone prophylactic antibiotics in favor of tailored therapies based on patient comorbidities in efforts to minimize bacterial burden, encrustation, and complications of ureteral stents.

RevDate: 2020-11-18

Patin NV, Peña-Gonzalez A, Hatt JK, et al (2020)

The Role of the Gut Microbiome in Resisting Norovirus Infection as Revealed by a Human Challenge Study.

mBio, 11(6):.

Norovirus infections take a heavy toll on worldwide public health. While progress has been made toward understanding host responses to infection, the role of the gut microbiome in determining infection outcome is unknown. Moreover, data are lacking on the nature and duration of the microbiome response to norovirus infection, which has important implications for diagnostics and host recovery. Here, we characterized the gut microbiomes of subjects enrolled in a norovirus challenge study. We analyzed microbiome features of asymptomatic and symptomatic individuals at the genome (population) and gene levels and assessed their response over time in symptomatic individuals. We show that the preinfection microbiomes of subjects with asymptomatic infections were enriched in Bacteroidetes and depleted in Clostridia relative to the microbiomes of symptomatic subjects. These compositional differences were accompanied by differences in genes involved in the metabolism of glycans and sphingolipids that may aid in host resilience to infection. We further show that microbiomes shifted in composition following infection and that recovery times were variable among human hosts. In particular, Firmicutes increased immediately following the challenge, while Bacteroidetes and Proteobacteria decreased over the same time. Genes enriched in the microbiomes of symptomatic subjects, including the adenylyltransferase glgC, were linked to glycan metabolism and cell-cell signaling, suggesting as-yet unknown roles for these processes in determining infection outcome. These results provide important context for understanding the gut microbiome role in host susceptibility to symptomatic norovirus infection and long-term health outcomes.IMPORTANCE The role of the human gut microbiome in determining whether an individual infected with norovirus will be symptomatic is poorly understood. This study provides important data on microbes that distinguish asymptomatic from symptomatic microbiomes and links these features to infection responses in a human challenge study. The results have implications for understanding resistance to and treatment of norovirus infections.

RevDate: 2020-11-18

Ma Y, Zhao J, Y Ma (2020)

MHSNMF: multi-view hessian regularization based symmetric nonnegative matrix factorization for microbiome data analysis.

BMC bioinformatics, 21(Suppl 6):234 pii:10.1186/s12859-020-03555-w.

BACKGROUND: With the rapid development of high-throughput technique, multiple heterogeneous omics data have been accumulated vastly (e.g., genomics, proteomics and metabolomics data). Integrating information from multiple sources or views is challenging to obtain a profound insight into the complicated relations among micro-organisms, nutrients and host environment. In this paper we propose a multi-view Hessian regularization based symmetric nonnegative matrix factorization algorithm (MHSNMF) for clustering heterogeneous microbiome data. Compared with many existing approaches, the advantages of MHSNMF lie in: (1) MHSNMF combines multiple Hessian regularization to leverage the high-order information from the same cohort of instances with multiple representations; (2) MHSNMF utilities the advantages of SNMF and naturally handles the complex relationship among microbiome samples; (3) uses the consensus matrix obtained by MHSNMF, we also design a novel approach to predict the classification of new microbiome samples.

RESULTS: We conduct extensive experiments on two real-word datasets (Three-source dataset and Human Microbiome Plan dataset), the experimental results show that the proposed MHSNMF algorithm outperforms other baseline and state-of-the-art methods. Compared with other methods, MHSNMF achieves the best performance (accuracy: 95.28%, normalized mutual information: 91.79%) on microbiome data. It suggests the potential application of MHSNMF in microbiome data analysis.

CONCLUSIONS: Results show that the proposed MHSNMF algorithm can effectively combine the phylogenetic, transporter, and metabolic profiles into a unified paradigm to analyze the relationships among different microbiome samples. Furthermore, the proposed prediction method based on MHSNMF has been shown to be effective in judging the types of new microbiome samples.

RevDate: 2020-11-17

van Soest APM, Hermes GDA, Berendsen AAM, et al (2020)

Associations between Pro- and Anti-Inflammatory Gastro-Intestinal Microbiota, Diet, and Cognitive Functioning in Dutch Healthy Older Adults: The NU-AGE Study.

Nutrients, 12(11): pii:nu12113471.

Dietary modulation of the gastro-intestinal microbiota is a potential target in improving healthy ageing and age-related functional outcomes, including cognitive decline. We explored the association between diet, gastro-intestinal microbiota and cognition in Dutch healthy older adults of the 'New dietary strategies addressing the specific needs of the elderly population for healthy aging in Europe' (NU-AGE) study. The microbiota profile of 452 fecal samples from 226 subjects was determined using a 16S ribosomal RNA gene-targeted microarray. Dietary intake was assessed by 7-day food records. Cognitive functioning was measured with an extensive cognitive test battery. We observed a dietary and microbial pro- to anti-inflammatory gradient associated with diets richer in animal- or plant-based foods. Fresh fruits, nuts, seeds and peanuts, red and processed meat and grain products were most strongly associated to microbiota composition. Plant-rich diets containing fresh fruits, nuts, seeds and peanuts were positively correlated with alpha-diversity, various taxa from the Bacteroidetes phylum and anti-inflammatory species, including those related to Faecalibacterium prausnitzii and Eubacterium rectale and E. biforme. Animal product-rich diets associated with pro-inflammatory species, including those related to Ruminococcus gnavus and Collinsella spp.. Cognition was neither associated with microbiota composition nor alpha-diversity. In conclusion, diets richer in animal- and plant-based foods were related to a pro- and anti-inflammatory microbial profile, while cognition was associated with neither.

RevDate: 2020-11-17

Krishnamoorthy M, Lenehan JG, Burton JP, et al (2020)

Immunomodulation in Pancreatic Cancer.

Cancers, 12(11): pii:cancers12113340.

Pancreatic cancer has a high mortality rate, and its incidence is increasing worldwide. The almost universal poor prognosis of pancreatic cancer is partly due to symptoms presenting only at late stages and limited effective treatments. Recently, immune checkpoint blockade inhibitors have drastically improved patient survival in metastatic and advanced settings in certain cancers. Unfortunately, these therapies are ineffective in pancreatic cancer. However, tumor biopsies from long-term survivors of pancreatic cancer are more likely to be infiltrated by cytotoxic T-cells and certain species of bacteria that activate T-cells. These observations suggest that T-cell activation is essential for anti-tumor immunity in pancreatic cancers. This review discusses the immunological mechanisms responsible for effective anti-tumor immunity and how immune-based strategies can be exploited to develop new pancreatic cancer treatments.

RevDate: 2020-11-16

Collins SL, Walsh JP, Renaud JB, et al (2020)

Improved methods for biomarker analysis of the big five mycotoxins enables reliable exposure characterization in a population of childbearing age women in Rwanda.

Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association pii:S0278-6915(20)30744-4 [Epub ahead of print].

Of the five agriculturally important mycotoxins, AFB1, FB1, DON, ZEA and OTA, a well-characterized biomarker of exposure in blood is only available for aflatoxin. Working with a population of 139 women of childbearing age in Rwanda, we undertook a comprehensive assessment of their dietary mycotoxin exposure. Using high-resolution LC-MS/MS with stable isotope dilution analysis, the albumin-aflatoxin adduct was quantitated in plasma. Similarly, AFM1, AFB1, AFG1, FB1 and B2, OTA, zearalenone, α-zearalenol, deoxynivalenol, deoxynivalenol-15-glucuronide and deoxynivalenol-3-glucuronide were quantitated in urine. AFB1-Lys was detected in plasma from 81% of the women, indicative of exposures 1-2 orders of magnitude above current guidance. Zearalenone and/or α-zearalenol were detected in the urine of 61% of the women, the majority of whom had estimated exposures 2-5 times the PMTDI, with one third, more than an order of magnitude above. Urinary deoxynivalenol or the two glucuronide conjugates were found in 77% of the participants. Of these, 60% were below the PMTDI, 28% were twice and 12% were >10x the PMTDI. Fumonisin B1 (30%) and ochratoxin A (71%) were also detected in urine. Exposures observed in these Rwandan women raise serious food safety concerns and highlight the need for authorities to help manage multiple mycotoxins in their diet.

RevDate: 2020-11-16

Irfan M, Delgado RZR, J Frias-Lopez (2020)

The Oral Microbiome and Cancer.

Frontiers in immunology, 11:591088.

There is mounting evidence that members of the human microbiome are highly associated with a wide variety of cancer types. Among oral cancers, oral squamous cell carcinoma (OSCC) is the most prevalent and most commonly studied, and it is the most common malignancy of the head and neck worldwide. However, there is a void regarding the role that the oral microbiome may play in OSCC. Previous studies have not consistently found a characteristic oral microbiome composition associated with OSCC. Although a direct causality has not been proven, individual members of the oral microbiome are capable of promoting various tumorigenic functions related to cancer development. Two prominent oral pathogens, Porphyromonas gingivalis, and Fusobacterium nucleatum can promote tumor progression in mice. P. gingivalis infection has been associated with oro-digestive cancer, increased oral cancer invasion, and proliferation of oral cancer stem cells. The microbiome can influence the evolution of the disease by directly interacting with the human body and significantly altering the response and toxicity to various forms of cancer therapy. Recent studies have shown an association of certain phylogenetic groups with the immunotherapy treatment outcomes of certain tumors. On the other side of the coin, recently it has been a resurgence in interest on the potential use of bacteria to cure cancer. These kinds of treatments were used in the late nineteenth and early twentieth centuries as the first line of defense against cancer in some hospitals but later displaced by other types of treatments such as radiotherapy. Currently, organisms such as Salmonella typhimurium and Clostridium spp. have been used for targeted strategies as potential vectors to treat cancer. In this review, we briefly summarize our current knowledge of the role of the oral microbiome, focusing on its bacterial fraction, in cancer in general and in OSCC more precisely, and a brief description of the potential use of bacteria to target tumors.

RevDate: 2020-11-16

Petrie KL (2020)

There're CRISPRs in My Yogurt: A Discovery-Based CURE at the Intersection of Industrial Food Production and the Human Microbiome.

Frontiers in microbiology, 11:578737.

Support for undergraduate laboratory education based on a CURE (Course-based Undergraduate Research Experience) model is more widespread than ever. By giving students the opportunity to conduct genuine research in laboratory courses they are required to take, CUREs can expose more students to scientific practice and have the potential to make science more inclusive, especially when research topics have direct impact on students' lives. Here, I present a new microbiology CURE module where students explore the real-world intersection between industrial food production and the human microbiome. In this module, students sequence CRISPR arrays in the genomes of lactic acid bacteria they isolate from yogurt. Natural CRISPRs (Clustered Regularly Interspaced Short Palindromic Repeats) act as the bacterial immune system. When a bacterial cell survives viral infection, it can incorporate a bit of that virus's DNA into its own genome, and produce small RNA guides that surveil the cell, ready to deploy virus-destroying enzymes if matching DNA from a fresh viral infection is detected. This viral immunity is of particular interest in the fermentation industry, since viral infection can destroy stocks of starter cultures and batches of product. Commercial producers of lactic acid bacteria for yogurt production often endeavor to produce strains with large CRISPR arrays and robust immunities. With this context, students are given the task of cataloging the viral immunities found in both commercial and traditionally produced yogurt, and exploring their potential impact on human health. Wet-lab practices (strain isolation, PCR, and Sanger sequencing) are combined with bioinformatic and literature sleuthing to identify the viruses to which bacteria are immune and explore whether consumption of these strains could impact human health via interactions with the human microbiome. Here, a detailed implementation of the module is presented with guides for educators and students.

RevDate: 2020-11-14

Coe GL, Pinkham NV, Celis AI, et al (2020)

Dynamic gut microbiome changes to low-iron challenge.

Applied and environmental microbiology pii:AEM.02307-20 [Epub ahead of print].

Iron is an essential micronutrient for life. In mammals, dietary iron is primarily absorbed in the small intestine. Currently, the impacts of dietary iron on the taxonomic structure and function of the gut microbiome and reciprocal effects on the animal host are not well understood. Here, we establish a mouse model of low-iron challenge in which intestinal biomarkers and reduced fecal iron reveal iron stress while serum iron and mouse behavioral markers indicate maintenance of iron homeostasis. We show that the diversity of the gut microbiome in conventional C57BL/6 mice changes dramatically during two-weeks on a low-iron diet. We also show the effects of a low-iron diet on microbiome diversity are long-lasting and not easily recovered when iron is returned to the diet. Finally, after optimizing taxon association methods, we show that some bacteria are unable to fully recover after the low-iron challenge and appear to be extirpated from the gut entirely. In particular, OTUs from the Prevotellaceae and Porphyromonadaceae families and Bacteroidales order are highly sensitive to low-iron conditions, while other seemingly insensitive OTUs recover. These results provide new insights into the iron requirements of gut microbiome members and add to the growing understanding of mammalian iron cycling.IMPORTANCE All cells need iron. Both too much iron and too little lead to diseases and unwanted outcomes. Although the impact of dietary iron on human cells and tissues has been well studied, there is currently a lack of understanding about how different levels of iron influence the abundant and diverse members of the human microbiome. This study develops a well-characterized mouse model for studying low-iron levels and identifies key groups of bacteria that are most affected. We found that the microbiome undergoes large changes when iron is removed from the diet but that many individual bacteria are able to rebound when iron levels are changed by to normal. That said, a select few members, referred to as "iron-sensitive" bacteria seem to be lost. This study begins to identify individual members of the mammalian microbiome most affected by changes in dietary iron levels.

RevDate: 2020-11-13

A James S, Phillips S, Telatin A, et al (2020)

Preterm Infants Harbour a Rapidly Changing Mycobiota That Includes Candida Pathobionts.

Journal of fungi (Basel, Switzerland), 6(4): pii:jof6040273.

Fungi and the mycobiome are a fundamental part of the human microbiome that contributes to human health and development. Despite this, relatively little is known about the mycobiome of the preterm infant gut. Here, we have characterised faecal fungal communities present in 11 premature infants born with differing degrees of prematurity and mapped how the mycobiome develops during early infancy. Using an ITS1 sequencing-based approach, the preterm infant gut mycobiome was found to be often dominated by a single species, typically a yeast. Candida was the most abundant genus, with the pathobionts C.albicans and C.parapsilosis highly prevalent and persistent in these infants. Gestational maturity at birth affected the distribution and abundance of these Candida, with hospital-associated C.parapsilosis more prevalent and abundant in infants born at less than 31 weeks. Fungal diversity was lowest at 6 months, but increased with age and change of diet, with food-associated Saccharomycescerevisiae most abundant in infants post weaning. This study provides a first insight into the fungal communities present within the preterm infant gut, identifying distinctive features including the prominence of pathobiont species, and the influence age and environmental factors play in shaping the development of the mycobiome.

RevDate: 2020-11-12

Nicolaro M, Portal DE, Shinder B, et al (2020)

The human microbiome and genitourinary malignancies.

Annals of translational medicine, 8(19):1245.

The human microbiome contains a vast network of understudied organisms that have an intimate role in our health and wellness. These microbiomes differ greatly between individuals, creating what may be thought of as a unique and dynamic microbial signature. Microbes have been shown to have various roles in metabolism, local and systemic inflammation, as well as immunity. Recent findings have confirmed the importance of both the gut and urinary microbiomes in genitourinary malignancies. Numerous studies have identified differences in microbial signatures between healthy patients and those with urologic malignancies. The microbiomes have been shown to contain microbes that may contribute to the etiology of disease state as well as yield information in regard to a person's health and their responsiveness to certain drugs such as immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs). Less well understood are the effects of antibiotics on oncologic outcomes in such treatment courses. This review will explore our current understanding and advancements in the field of microbiome research and discuss its intimate association with genitourinary diseases including bladder cancer, prostate cancer, and kidney cancer. With a better understanding of the association between the microbiome and genitourinary malignancy, further investigation may produce reliable predictors of disease, prognostic indicators as well as therapeutic targets.

RevDate: 2020-11-12

Sikakana P, RA Roberts (2020)

A decade of toxicological trends: what the papers say.

Toxicology research, 9(5):676-682 pii:tfaa063.

Here we look at popular trends and concepts in toxicology over the decade 2009-2019. The top 10 concepts included methodological approaches such as zebrafish and genomics as well as broader concepts such as personalized medicine and adverse outcome pathways. The total number and rank order for each of the top 10 were tracked year by year via PubMed with >9500 papers contributing to the analysis. The data revealed a slow upward trend in the number of papers across all the concepts from 260 in 2009 to >1700 in 2019. Zebrafish, genomics and personalized medicine remained in the top four slots since 2009 with zebrafish dominating the rankings over the entire decade. Genomics was a strong second until 2013 when it was displaced first by the microbiome in 2014 and secondly by personalized medicine in 2015. Other notable trends were the ascendancy of the microbiome and adverse outcome pathways and the descendancy of hormesis and the 3Rs (replacement, reduction and refinement of animals in testing). The observation that the top four slots have been static over the past 4 years suggests that new ideas are introduced and increase in popularity until they find their place in scientific culture. This may suggest that relatively new concepts such as artificial intelligence and microphysiological systems have yet to find their steady state in the rankings. Similarly, as a relatively new player in toxicology, the full impact of the human microbiome on drug efficacy and safety remains to be seen.

RevDate: 2020-11-12

Stokholm J, Thorsen J, Blaser MJ, et al (2020)

Delivery mode and gut microbial changes correlate with an increased risk of childhood asthma.

Science translational medicine, 12(569):.

There have been reports of associations between cesarean section delivery and the risk of childhood asthma, potentially mediated through changes in the gut microbiota. We followed 700 children in the Copenhagen Prospective Studies on Asthma in Childhood2010 (COPSAC2010) cohort prospectively from birth. We examined the effects of cesarean section delivery on gut microbial composition by 16S rRNA gene amplicon sequencing during the first year of life. We then explored whether gut microbial perturbations due to delivery mode were associated with a risk of developing asthma in the first 6 years of life. Delivery by cesarean section was accompanied by marked changes in gut microbiota composition at one week and one month of age, but by one year of age only minor differences persisted compared to vaginal delivery. Increased asthma risk was found in children born by cesarean section only if their gut microbiota composition at 1 year of age still retained a cesarean section microbial signature, suggesting that appropriate maturation of the gut microbiota could mitigate against the increased asthma risk associated with gut microbial changes due to cesarean section delivery.

RevDate: 2020-11-11

Hadrup N, Aimonen K, Ilves M, et al (2020)

Pulmonary toxicity of synthetic amorphous silica - effects of porosity and copper oxide doping.

Nanotoxicology [Epub ahead of print].

Materials can be modified for improved functionality. Our aim was to test whether pulmonary toxicity of silica nanomaterials is increased by the introduction of: a) porosity; and b) surface doping with CuO; and whether c) these modifications act synergistically. Mice were exposed by intratracheal instillation and for some doses also oropharyngeal aspiration to: 1) solid silica 100 nm; 2) porous silica 100 nm; 3) porous silica 100 nm with CuO doping; 4) solid silica 300 nm; 5) porous silica 300 nm; 6) solid silica 300 nm with CuO doping; 7) porous silica 300 nm with CuO doping; 8) CuO nanoparticles 9.8 nm; or 9) carbon black Printex 90 as benchmark. Based on a pilot study, dose levels were between 0.5 and 162 µg/mouse (0.2 and 8.1 mg/kg bw). Endpoints included pulmonary inflammation (neutrophil numbers in bronchoalveolar fluid), acute phase response, histopathology, and genotoxicity assessed by the comet assay, micronucleus test, and the gamma-H2AX assay. The porous silica materials induced greater pulmonary inflammation than their solid counterparts. A similar pattern was seen for acute phase response induction and histologic changes. This could be explained by a higher specific surface area per mass unit for the most toxic particles. CuO doping further increased the acute phase response normalized according to the deposited surface area. We identified no consistent evidence of synergism between surface area and CuO doping. In conclusion, porosity and CuO doping each increased the toxicity of silica nanomaterials and there was no indication of synergy when the modifications co-occurred.

RevDate: 2020-11-11

Brandt K, R Barrangou (2020)

Adaptive response to iterative passages of five Lactobacillus species in simulated vaginal fluid.

BMC microbiology, 20(1):339 pii:10.1186/s12866-020-02027-8.

BACKGROUND: Microbiome and metagenomic studies have given rise to a new understanding of microbial colonization of various human tissues and their ability to impact our health. One human microbiome growing in notoriety, the vaginal microbiome, stands out given its importance for women's health, and is peculiar in terms of its relative bacterial composition, including its simplicity and typical domination by a small number of Lactobacillus species. The loss of Lactobacillus dominance is associated with disorders such as bacterial vaginosis, and efforts are now underway to understand the ability of Lactobacillus species to colonize the vaginal tract and adapt to this dynamic and acidic environment. Here, we investigate how various Lactobacillus species often isolated from the vaginal and intestinal cavities genomically and transcriptionally respond to iterative growth in simulated vaginal fluid.

RESULTS: We determined the genomes and transcriptomes of L. acidophilus, L. crispatus, L. fermentum, L. gasseri, and L. jensenii and compared profiles after 50, 100, 500, and 1000 generations of iterative passages in synthetic vaginal fluid. In general, we identified relatively few genetic changes consisting of single nucleotide polymorphisms, with higher counts occurring more frequently in non-vaginal isolated species. Transcriptional profiles were more impacted over time and tended to be more extensive for species that typically do not dominate the vaginal tract, reflecting a more extensive need to adapt to a less familiar environment.

CONCLUSIONS: This study provides insights into how vaginal and non-vaginal Lactobacillus species respond and adapt to a simulated vaginal environment. Overall, trends indicate high genomic stability for all species involved, with more variability in the transcriptome especially for non-dominant species of the vaginal tract.

RevDate: 2020-11-09

Lane MM, Davis JA, Beattie S, et al (2020)

Ultraprocessed food and chronic noncommunicable diseases: A systematic review and meta-analysis of 43 observational studies.

Obesity reviews : an official journal of the International Association for the Study of Obesity [Epub ahead of print].

This systematic review and meta-analysis investigated the association between consumption of ultraprocessed food and noncommunicable disease risk, morbidity and mortality. Forty-three observational studies were included (N = 891,723): 21 cross-sectional, 19 prospective, two case-control and one conducted both a prospective and cross-sectional analysis. Meta-analysis demonstrated consumption of ultraprocessed food was associated with increased risk of overweight (odds ratio: 1.36; 95% confidence interval [CI], 1.23-1.51; P < 0.001), obesity (odds ratio: 1.51; 95% CI, 1.34-1.70; P < 0.001), abdominal obesity (odds ratio: 1.49; 95% CI, 1.34-1.66; P < 0.0001), all-cause mortality (hazard ratio: 1.28; 95% CI, 1.11-1.48; P = 0.001), metabolic syndrome (odds ratio: 1.81; 95% CI, 1.12-2.93; P = 0.015) and depression in adults (hazard ratio: 1.22; 95% CI, 1.16-1.28, P < 0.001) as well as wheezing (odds ratio: 1.40; 95% CI, 1.27-1.55; P < 0.001) but not asthma in adolescents (odds ratio: 1.20; 95% CI, 0.99-1.46; P = 0.065). In addition, consumption of ultraprocessed food was associated with cardiometabolic diseases, frailty, irritable bowel syndrome, functional dyspepsia and cancer (breast and overall) in adults while also being associated with metabolic syndrome in adolescents and dyslipidaemia in children. Although links between ultraprocessed food consumption and some intermediate risk factors in adults were also highlighted, further studies are required to more clearly define associations in children and adolescents. STUDY REGISTRATION: Prospero ID: CRD42020176752.

RevDate: 2020-11-09

Zhang X, Guo B, N Yi (2020)

Zero-Inflated gaussian mixed models for analyzing longitudinal microbiome data.

PloS one, 15(11):e0242073 pii:PONE-D-20-20512.

MOTIVATION: The human microbiome is variable and dynamic in nature. Longitudinal studies could explain the mechanisms in maintaining the microbiome in health or causing dysbiosis in disease. However, it remains challenging to properly analyze the longitudinal microbiome data from either 16S rRNA or metagenome shotgun sequencing studies, output as proportions or counts. Most microbiome data are sparse, requiring statistical models to handle zero-inflation. Moreover, longitudinal design induces correlation among the samples and thus further complicates the analysis and interpretation of the microbiome data.

RESULTS: In this article, we propose zero-inflated Gaussian mixed models (ZIGMMs) to analyze longitudinal microbiome data. ZIGMMs is a robust and flexible method which can be applicable for longitudinal microbiome proportion data or count data generated with either 16S rRNA or shotgun sequencing technologies. It can include various types of fixed effects and random effects and account for various within-subject correlation structures, and can effectively handle zero-inflation. We developed an efficient Expectation-Maximization (EM) algorithm to fit the ZIGMMs by taking advantage of the standard procedure for fitting linear mixed models. We demonstrate the computational efficiency of our EM algorithm by comparing with two other zero-inflated methods. We show that ZIGMMs outperform the previously used linear mixed models (LMMs), negative binomial mixed models (NBMMs) and zero-inflated Beta regression mixed model (ZIBR) in detecting associated effects in longitudinal microbiome data through extensive simulations. We also apply our method to two public longitudinal microbiome datasets and compare with LMMs and NBMMs in detecting dynamic effects of associated taxa.

RevDate: 2020-11-09

Witjes JJ, Smits LP, Pekmez CT, et al (2020)

Donor Fecal Microbiota Transplantation Alters Gut Microbiota and Metabolites in Obese Individuals With Steatohepatitis.

Hepatology communications, 4(11):1578-1590 pii:HEP41601.

The intestinal microbiota has been linked to the development and prevalence of steatohepatitis in humans. Interestingly, steatohepatitis is significantly lower in individuals taking a plant-based, low-animal-protein diet, which is thought to be mediated by gut microbiota. However, data on causality between these observations in humans is scarce. In this regard, fecal microbiota transplantation (FMT) using healthy donors is safe and is capable of changing microbial composition in human disease. We therefore performed a double-blind randomized controlled proof-of-principle study in which individuals with hepatic steatosis on ultrasound were randomized to two study arms: lean vegan donor (allogenic n = 10) or own (autologous n = 11) FMT. Both were performed three times at 8-week intervals. A liver biopsy was performed at baseline and after 24 weeks in every subject to determine histopathology (Nonalcoholic Steatohepatitis Clinical Research Network) classification and changes in hepatic gene expression based on RNA sequencing. Secondary outcome parameters were changes in intestinal microbiota composition and fasting plasma metabolomics. We observed a trend toward improved necro-inflammatory histology, and found significant changes in expression of hepatic genes involved in inflammation and lipid metabolism following allogenic FMT. Intestinal microbial community structure changed following allogenic FMT, which was associated with changes in plasma metabolites as well as markers of . Conclusion: Allogenic FMT using lean vegan donors in individuals with hepatic steatosis shows an effect on intestinal microbiota composition, which is associated with beneficial changes in plasma metabolites and markers of steatohepatitis.

RevDate: 2020-11-09

Zizzari IG, Filippo AD, Scirocchi F, et al (2020)

Soluble Immune Checkpoints, Gut Metabolites and Performance Status as Parameters of Response to Nivolumab Treatment in NSCLC Patients.

Journal of personalized medicine, 10(4): pii:jpm10040208.

Patients with non-small cell lung cancer (NSCLC) have been shown to benefit from the introduction of anti-PD1 treatment. However, not all patients experience tumor regression and durable response. The identification of a string of markers that are direct or indirect indicators of the immune system fitness is needed to choose optimal therapeutic schedules in the management of NSCLC patients. We analyzed 34 immuno-related molecules (14 soluble immune checkpoints, 17 cytokines/chemokines, 3 adhesion molecules) released in the serum of 22 NSCLC patients under Nivolumab treatment and the gut metabolomic profile at baseline. These parameters were correlated with performance status (PS) and/or response to treatment. Nivolumab affected the release of soluble immune checkpoints (sICs). Patients with a better clinical outcome and with an optimal PS (PS = 0) showed a decreased level of PD1 and maintained low levels of several sICs at first clinical evaluation. Low levels of PDL1, PDL2, Tim3, CD137 and BTLA4 were also correlated with a long response to treatment. Moreover, responding patients showed a high proportion of eubiosis-associated gut metabolites. In this exploratory study, we propose a combination of immunological and clinical parameters (sICs, PS and gut metabolites) for the identification of patients more suitable for Nivolumab treatment. This string of parameters validated in a network analysis on a larger cohort of patients could help oncologists to improve their decision-making in an NSCLC setting.

RevDate: 2020-11-06

Torralba MG, Aleti G, Li W, et al (2020)

Oral Microbial Species and Virulence Factors Associated with Oral Squamous Cell Carcinoma.

Microbial ecology pii:10.1007/s00248-020-01596-5 [Epub ahead of print].

The human microbiome has been the focus of numerous research efforts to elucidate the pathogenesis of human diseases including cancer. Oral cancer mortality is high when compared with other cancers, as diagnosis often occurs during late stages. Its prevalence has increased in the USA over the past decade and accounts for over 40,000 new cancer patients each year. Additionally, oral cancer pathogenesis is not fully understood and is likely multifactorial. To unravel the relationships that are associated with the oral microbiome and their virulence factors, we used 16S rDNA and metagenomic sequencing to characterize the microbial composition and functional content in oral squamous cell carcinoma (OSCC) tumor tissue, non-tumor tissue, and saliva from 18 OSCC patients. Results indicate a higher number of bacteria belonging to the Fusobacteria, Bacteroidetes, and Firmicutes phyla associated with tumor tissue when compared with all other sample types. Additionally, saliva metaproteomics revealed a significant increase of Prevotella in five OSCC subjects, while Corynebacterium was mostly associated with ten healthy subjects. Lastly, we determined that there are adhesion and virulence factors associated with Streptococcus gordonii as well as from known oral pathogens belonging to the Fusobacterium genera found mostly in OSCC tissues. From these results, we propose that not only will the methods utilized in this study drastically improve OSCC diagnostics, but the organisms and specific virulence factors from the phyla detected in tumor tissue may be excellent biomarkers for characterizing disease progression.

RevDate: 2020-11-05

Keller JJ, Ooijevaar RE, Hvas CL, et al (2020)

A standardised model for stool banking for faecal microbiota transplantation: a consensus report from a multidisciplinary UEG working group.

United European gastroenterology journal [Epub ahead of print].

BACKGROUND: Fecal microbiota transplantation is an emerging therapeutic option, particularly for the treatment of recurrent Clostridioides difficile infection. Stool banks that organise recruitment and screening of feces donors are being embedded within the regulatory frameworks described in the European Union Tissue and Cells Directive and the technical guide to the quality and safety of tissue and cells for human application, published by the European Council.

OBJECTIVE: Several European and international consensus statements concerning fecal microbiota transplantation have been issued. While these documents provide overall guidance, we aim to provide a detailed description of all processes that relate to the collection, handling and clinical application of human donor stool in this document.

METHODS: Collaborative subgroups of experts on stool banking drafted concepts for all domains pertaining to stool banking. During a working group meeting in the United European Gastroenterology Week 2019 in Barcelona, these concepts were discussed and finalised to be included in our overall guidance document about fecal microbiota transplantation.

RESULTS: A guidance document for all domains pertaining to stool banking was created. This document includes standard operating manuals for several processes involved with stool banking, such as handling of donor material, storage and donor screening.

CONCLUSION: The implementation of fecal microbiota transplantation by stool banks in concordance with our guidance document will enable quality assurance and guarantee the availability of donor feces preparations for patients.

RevDate: 2020-11-05

Vlasova AN, Rajashekara G, LJ Saif (2018)

Interactions between human microbiome, diet, enteric viruses and immune system: Novel insights from gnotobiotic pig research.

Drug discovery today. Disease models, 28:95-103.

Studies over the past few decades demonstrated that gnotobiotic (Gn) pigs provide an unprecedented translational model to study human intestinal health and diseases. Due to the high degree of anatomical, physiological, metabolic, immunological, and developmental similarity, the domestic pig closely mimics the human intestinal microenvironment. Also, Gn piglets can be efficiently transplanted with human microbiota from infants, children and adults with resultant microbial profiles remarkably similar to the original human samples, a feat consistently not achievable in rodent models. Finally, Gn and human microbiota-associated (HMA) piglets are susceptible to human enteric viral pathogens (including human rotavirus, HRV) and can be fed authentic human diets, which further increases the translational potential of these models. In this review, we will focus on recent studies that evaluated the pathophysiology of protein malnutrition and the associated dysbiosis and immunological dysfunction in neonatal HMA piglets. Additionally, we will discuss studies of potential dietary interventions that moderate the effects of malnutrition and dysbiosis on antiviral immunity and HRV vaccines in HMA pigs. Such studies provide novel models and novel mechanistic insights critical for development of drug interventions.

RevDate: 2020-11-04

Manus MB, Kuthyar S, Perroni-Marañón AG, et al (2020)

Infant Skin Bacterial Communities Vary by Skin Site and Infant Age across Populations in Mexico and the United States.

mSystems, 5(6):.

Daily practices put humans in close contact with the surrounding environment, and differences in these practices have an impact on human physiology, development, and health. There is mounting evidence that the microbiome represents an interface that mediates interactions between the human body and the environment. In particular, the skin microbiome serves as the primary interface with the external environment and aids in host immune function by contributing as the first line of defense against pathogens. Despite these important connections, we have only a basic understanding of how the skin microbiome is first established, or which environmental factors contribute to its development. To this end, this study compared the skin bacterial communities of infants (n = 47) living in four populations in Mexico and the United States that span the socioeconomic gradient, where we predicted that variation in physical and social environments would shape the infant skin microbiome. Results of 16S rRNA bacterial gene sequencing on 119 samples (armpit, hand, and forehead) showed that infant skin bacterial diversity and composition are shaped by population-level factors, including those related to socioeconomic status and household composition, and vary by skin site and infant age. Differences in infant-environment interactions, including with other people, appear to vary across the populations, likely influencing infant microbial exposures and, in turn, the composition of infant skin bacterial communities. These findings suggest that variation in microbial exposures stemming from the local environment in infancy can impact the establishment of the skin microbiome across body sites, with implications for developmental and health outcomes.IMPORTANCE This study contributes to the sparse literature on the infant skin microbiome in general, and the virtually nonexistent literature on the infant skin microbiome in a field setting. While microbiome research often addresses patterns at a national scale, this study addresses the influence of population-level factors, such as maternal socioeconomic status and contact with caregivers, on infant skin bacterial communities. This approach strengthens our understanding of how local variables influence the infant skin microbiome, and paves the way for additional studies to combine biological sample collection with questionnaires to adequately capture how specific behaviors dictate infant microbial exposures. Work in this realm has implications for infant care and health, as well as for investigating how the microbial communities of different body sites develop over time, with applications to specific health outcomes associated with the skin microbiome (e.g., immune system development or atopic dermatitis).

RevDate: 2020-11-03

North OI, AR Davidson (2020)

Phage proteins required for tail fiber assembly also bind specifically to the surface of host bacterial strains.

Journal of bacteriology pii:JB.00406-20 [Epub ahead of print].

To initiate their life cycle, phages must specifically bind to the surface of their bacterial hosts. Long-tailed phages often interact with the cell surface using fibers, which are elongated intertwined trimeric structures. The folding and assembly of these complex structures generally requires the activity of an intra- or intermolecular chaperone protein. Tail fiber assembly (Tfa) proteins are a very large family of proteins that serve as chaperones for fiber folding in a wide variety of phages infecting diverse species. A recent structural study showed that the Tfa protein from E. coli phage Mu (TfaMu) mediates fiber folding and stays bound to the distal tip of the fiber, becoming a component of the mature phage particle. This finding revealed the potential for TfaMu to also play a role in cell surface binding. To address this issue, here we have shown that TfaMu binds to lipopolysaccharide (LPS), the cell surface receptor of phage Mu with a similar strength as the fiber itself. Furthermore, we have found that TfaMu and the Tfa protein from E. coli phage P2 bind LPS with distinct specificities that mirror the host specificity of these two phages. By comparing the sequences of these two proteins, which are 93% identical, we identified a single residue that is responsible for their distinct LPS-binding behaviours. Although we have not yet found conditions under which Tfa proteins influence host range, the potential for such a role is now evident as we have demonstrated their ability to bind LPS in a strain-specific manner.Importance With the growing interest in using phages to combat antibiotic-resistant infections or manipulate the human microbiome, establishing approaches for the modification of phage host range has become an important research topic. Tfa proteins are a large family of proteins known previously to function as chaperones for the folding of phage fibers, which are crucial determinants of host range for long-tailed phages. Here we reveal that some Tfa proteins are bi-functional with the additional activity of binding to LPS, the surface binding receptor for many phages. This discovery opens up new potential avenues for altering phage host range through engineering of the surface binding specificity of Tfa proteins.

RevDate: 2020-11-02

Rooney CM, Mankia K, P Emery (2020)

The Role of the Microbiome in Driving RA-Related Autoimmunity.

Frontiers in cell and developmental biology, 8:538130.

Once referred to as "normal commensal flora" the human microbiome plays an integral role between health and disease. The host mucosal surface replete with a multitude of immune cells is a vast arena constantly sensing and responding to antigen presentation and microbial by-products. It is this key role that may allow the microbiome to prime or protect the host from autoimmune disease. Rheumatoid arthritis (RA) is a chronic, disabling inflammatory condition characterized by a complex multifactorial etiology. The presence of certain genetic markers has been proven to increase susceptibility to RA however it does not guarantee disease development. Given low concordance rates demonstrated in monozygotic twin studies there is a clear implication for the involvement of external players in RA pathogenesis. Since the historical description of rheumatoid factor, numerous additional autoantibodies have been described in the sera of RA patients. The presence of anti-cyclic citrullinated protein antibody is now a standard test, and is associated with a more severe disease course. Interestingly these antibodies are detectable in patient's sera long before the clinical signs of RA occur. The production of autoantibodies is driven by the lack of tolerance of the immune system, and how tolerance is broken is a crucial question for understanding RA development. Here we review current literature on the role of the microbiome in RA development including periodontal, gut and lung mucosa, with particular focus on proposed mechanisms of host microbiome interactions. We discuss the use of Mendelian randomization to assign causality to the microbiome and present considerations for future studies.

RevDate: 2020-11-02

Pietro Merli , Lorenza Putignani , Annalisa Ruggeri , et al (2020)

Decolonization of multi-drug resistant bacteria by fecal microbiota transplantation in five pediatric patients before allogeneic hematopoietic stem cell transplantation: gut microbiota profiling, infectious and clinical outcomes.

Haematologica, 105(11):2686-2690.

RevDate: 2020-10-30

Spencer SP, JL Sonnenburg (2020)

When Gut Microbiota Creep into Fat, the Fat Creeps Back.

Cell, 183(3):589-591.

Ha and colleagues describe a previously unappreciated diversity of microbes in the mesenteric adipose tissue (MAT) surrounding the GI tract. Viable bacteria that are mislocalized from the gut microbiota and metabolically adapted to the MAT contribute to the "creeping fat" of Crohn's disease.

RevDate: 2020-10-31

Saladié M, Caparrós-Martín JA, Agudelo-Romero P, et al (2020)

Microbiomic Analysis on Low Abundant Respiratory Biomass Samples; Improved Recovery of Microbial DNA From Bronchoalveolar Lavage Fluid.

Frontiers in microbiology, 11:572504.

In recent years the study of the commensal microbiota is driving a remarkable paradigm shift in our understanding of human physiology. However, intrinsic technical difficulties associated with investigating the Microbiomics of some body niches are hampering the development of new knowledge. This is particularly the case when investigating the functional role played by the human microbiota in modulating the physiology of key organ systems. A major hurdle in investigating specific Microbiome communities is linked to low bacterial density and susceptibility to bias caused by environmental contamination. To prevent such inaccuracies due to background processing noise, harmonized tools for Microbiomic and bioinformatics practices have been recommended globally. The fact that the impact of this undesirable variability is negatively correlated with the DNA concentration in the sample highlights the necessity to improve existing DNA isolation protocols. In this report, we developed and tested a protocol to more efficiently recover bacterial DNA from low volumes of bronchoalveolar lavage fluid obtained from infants and adults. We have compared the efficiency of the described method with that of a commercially available kit for microbiome analysis in body fluids. We show that this new methodological approach performs better in terms of extraction efficiency. As opposed to commercial kits, the DNA extracts obtained with this new protocol were clearly distinguishable from the negative extraction controls in terms of 16S copy number and Microbiome community profiles. Altogether, we described a cost-efficient protocol that can facilitate microbiome research in low-biomass human niches.

RevDate: 2020-10-29

Chowdhury S, SS Fong (2020)

Leveraging genome-scale metabolic models for human health applications.

Current opinion in biotechnology, 66:267-276 pii:S0958-1669(20)30131-2 [Epub ahead of print].

Genome-scale metabolic modeling is a scalable and extensible computational method for analyzing and predicting biological function. With the ongoing improvements in computational methods and experimental capabilities, genome-scale metabolic models (GEMs) are demonstrating utility in addressing human health applications. The initial areas of highest impact are likely to be health applications where disease states involve metabolic changes. In this review, we focus on recent application of GEMs to studying cancer and the human microbiome by describing the enabling methodologies and outcomes of these studies. We conclude with proposing some areas of research that are likely to arise as a result of recent methodological advances.

RevDate: 2020-10-29

Schwarz M, Murphy EJ, Foley AM, et al (2020)

Exploring the synthetic potential of a marine transaminase including discrimination at a remote stereocentre.

Organic & biomolecular chemistry [Epub ahead of print].

The marine transaminase, P-ω-TA, can be employed for the transamination from 1-aminotetralins and 1-aminoindanes with differentiation of stereochemistry at both the site of reaction and at a remote stereocentre resulting in formation of ketone products with up to 93% ee. While 4-substituents are tolerated on the tetralin core, the presence of 3- or 8-substituents is not tolerated by the transaminase. In general P-ω-TA shows capacity for remote diastereoselectivity, although both the stereoselectivity and efficiency are dependent on the specific substrate structure. Optimum efficiency and selectivity are seen with 4-haloaryl-1-aminotetralins and 3-haloaryl-1-aminoindanes, which may be associated with the marine origin of this enzyme.

RevDate: 2020-10-29

Amado PPP, Kawamoto D, Albuquerque-Souza E, et al (2020)

Oral and Fecal Microbiome in Molar-Incisor Pattern Periodontitis.

Frontiers in cellular and infection microbiology, 10:583761.

In order to improve our understanding on the microbial complexity associated with Grade C/molar-incisor pattern periodontitis (GC/MIP), we surveyed the oral and fecal microbiomes of GC/MIP and compared to non-affected individuals (Control). Seven Afro-descendants with GC/MIP and seven age/race/gender-matched controls were evaluated. Biofilms from supra/subgingival sites (OB) and feces were collected and submitted to 16S rRNA sequencing. Aggregatibacter actinomycetemcomitans (Aa) JP2 clone genotyping and salivary nitrite levels were determined. Supragingival biofilm of GC/MIP presented greater abundance of opportunistic bacteria. Selenomonas was increased in subgingival healthy sites of GC/MIP compared to Control. Synergistetes and Spirochaetae were more abundant whereas Actinobacteria was reduced in OB of GC/MIP compared to controls. Aa abundance was 50 times higher in periodontal sites with PD≥ 4 mm of GC/MIP than in controls. GC/MIP oral microbiome was characterized by a reduction in commensals such as Kingella, Granulicatella, Haemophilus, Bergeyella, and Streptococcus and enrichment in periodontopathogens, especially Aa and sulfate reducing Deltaproteobacteria. The oral microbiome of the Aa JP2-like+ patient was phylogenetically distant from other GC/MIP individuals. GC/MIP presented a higher abundance of sulfidogenic bacteria in the feces, such as Desulfovibrio fairfieldensis, Erysipelothrix tonsillarum, and Peptostreptococcus anaerobius than controls. These preliminary data show that the dysbiosis of the microbiome in Afro-descendants with GC/MIP was not restricted to affected sites, but was also observed in supragingival and subgingival healthy sites, as well as in the feces. The understanding on differences of the microbiome between healthy and GC/MIP patients will help in developing strategies to improve and monitor periodontal treatment.

RevDate: 2020-10-29

Yegorov S, Babenko D, Kozhakhmetov S, et al (2020)

Psoriasis Is Associated With Elevated Gut IL-1α and Intestinal Microbiome Alterations.

Frontiers in immunology, 11:571319.

Background: Psoriasis is a chronic inflammatory condition that predominantly affects the skin and is associated with extracutaneous disorders, such as inflammatory bowel disease and arthritis. Changes in gut immunology and microbiota are important drivers of proinflammatory disorders and could play a role in the pathogenesis of psoriasis. Therefore, we explored whether psoriasis in a Central Asian cohort is associated with alterations in select immunological markers and/or microbiota of the gut.

Methods: We undertook a case-control study of stool samples collected from outpatients, aged 30-45 years, of a dermatology clinic in Kazakhstan presenting with plaque, guttate, or palmoplantar psoriasis (n = 20), and age-sex matched subjects without psoriasis (n = 20). Stool supernatant was subjected to multiplex ELISA to assess the concentration of 47 cytokines and immunoglobulins and to 16S rRNA gene sequencing to characterize microbial diversity in both psoriasis participants and controls.

Results: The psoriasis group tended to have higher concentrations of most analytes in stool (29/47 = 61.7%) and gut IL-1α was significantly elevated (4.19-fold, p = 0.007) compared to controls. Levels of gut IL-1α in the psoriasis participants remained significantly unaltered up to 3 months after the first sampling (p = 0.430). Psoriasis was associated with alterations in gut Firmicutes, including elevated Faecalibacterium and decreased Oscillibacter and Roseburia abundance, but no association was observed between gut microbial diversity or Firmicutes/Bacteroidetes ratios and disease status.

Conclusions: Psoriasis may be associated with gut inflammation and dysbiosis. Studies are warranted to explore the use of gut microbiome-focused therapies in the management of psoriasis in this under-studied population.

RevDate: 2020-10-28

Hayes W, S Sahu (2020)

The Human Microbiome: History and Future.

Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques, 23:404-411.

The microbiome plays an important role in human health and disease. Our current understanding of the human microbiome is limited. A significant amount of progress has been made in this area of research in the last two decades. The human microbiome plays an important role in host metabolism and physiology. Recent studies suggest a critical relationship between the human microbiome and host metabolism. The interactions between the microbiome and host metabolism affect human health and disease. However, this review of the literature indicates that more studies are required using new technologies to have a greater understanding of the role the human microbiome plays in human health and disease.

RevDate: 2020-10-28

Brinkac LM, Rahman N, Chua LL, et al (2020)

Biomimetic Gut Model Systems for Development of Targeted Microbial Solutions for Enhancing Warfighter Health and Performance.

mSystems, 5(5):.

The human gut microbiome plays a vital role in both health and disease states and as a mediator of cognitive and physical performance. Despite major advances in our understanding of the role of gut microbes in host physiology, mechanisms underlying human-microbiome dynamics have yet to be fully elucidated. This knowledge gap represents a major hurdle to the development of targeted gut microbiome solutions influencing human health and performance outcomes. The microbiome as it relates to warfighter health and performance is of interest to the Department of Defense (DoD) with the development of interventions impacting gut microbiome resiliency among its top research priorities. While technological advancements are enabling the development of experimental model systems that facilitate mechanistic insights underpinning human health, disease, and performance, translatability to human outcomes is still questionable. This review discusses some of the drivers influencing the DoD's interest in the warfighter gut microbiome and describes current in vitro gut model systems supporting direct microbial-host interactions.

RevDate: 2020-10-25

Marco ML (2020)

Defining how microorganisms benefit human health.

Microbial biotechnology [Epub ahead of print].

An appreciation for how microorganisms can benefit human health has grown over the past century. The future of this research will be to identify the specific microbial enzymatic pathways and molecules necessary for health promotion. Some of these 'beneficial factors' are already known for probiotics and species in the human microbiome, however, precise descriptions of the mechanistic details for their effects remain to be discovered. The need for this research is elevated by the potential use of microorganisms for preventing and treating the non-communicable diseases which are now the leading causes of death worldwide.

RevDate: 2020-10-24

Kiljunen S (2020)

Editorial for the Special Issue: "Phage Therapy: A Biological Approach to Treatment of Bacterial Infections".

Antibiotics (Basel, Switzerland), 9(10): pii:antibiotics9100721.

The emergence of antibiotic-resistant bacteria presents a major challenge in terms of increased morbidity, mortality, and healthcare costs [...].

RevDate: 2020-10-23

Yang D, W Xu (2020)

Clustering on Human Microbiome Sequencing Data: A Distance-Based Unsupervised Learning Model.

Microorganisms, 8(10): pii:microorganisms8101612.

Modeling and analyzing human microbiome allows the assessment of the microbial community and its impacts on human health. Microbiome composition can be quantified using 16S rRNA technology into sequencing data, which are usually skewed and heavy-tailed with excess zeros. Clustering methods are useful in personalized medicine by identifying subgroups for patients stratification. However, there is currently a lack of standardized clustering method for the complex microbiome sequencing data. We propose a clustering algorithm with a specific beta diversity measure that can address the presence-absence bias encountered for sparse count data and effectively measure the sample distances for sample stratification. Our distance measure used for clustering is derived from a parametric based mixture model producing sample-specific distributions conditional on the observed operational taxonomic unit (OTU) counts and estimated mixture weights. The method can provide accurate estimates of the true zero proportions and thus construct a precise beta diversity measure. Extensive simulation studies have been conducted and suggest that the proposed method achieves substantial clustering improvement compared with some widely used distance measures when a large proportion of zeros is presented. The proposed algorithm was implemented to a human gut microbiome study on Parkinson's diseases to identify distinct microbiome states with biological interpretations.

RevDate: 2020-10-21

Del Chierico F, Grassini P, Quagliariello A, et al (2020)

The impact of intestinal microbiota on weight loss in Parkinson's disease patients: a pilot study.

Future microbiology, 15:1393-1404.

Background: There is increasing evidence of the association between microbiome dysfunction and Parkinson's disease (PD). Moreover, some PD patients suffer from unintentional weight loss (WL) which may precede the motor manifestations of the disease. Materials & methods: Gut microbiota profiling by 16S rRNA gene sequencing was performed in PD patients with an unintended WL, in steady weight patients (non-WL [NWL]) and in matched normal subjects. KEGG functional predictions were carried out. Results: Microbiota profiles revealed a dissimilarity between WL and NWL. Moreover, WL pathways were characterized by fatty acid biosynthesis, while NWL by inflammation pathways. Conclusion: The gut microbiota could participate in weight alteration observed in PD by the presence of bacteria involved in weight gain and inflammation, or conversely by bacteria implicated in energy expenditure.

RevDate: 2020-10-21

Deschamps C, Fournier E, Uriot O, et al (2020)

Comparative methods for fecal sample storage to preserve gut microbial structure and function in an in vitro model of the human colon.

Applied microbiology and biotechnology pii:10.1007/s00253-020-10959-4 [Epub ahead of print].

In vitro gut models, such as the mucosal artificial colon (M-ARCOL), provide timely and cost-efficient alternatives to in vivo assays allowing mechanistic studies to better understand the role of human microbiome in health and disease. Using such models inoculated with human fecal samples may require a critical step of stool storage. The effects of preservation methods on microbial structure and function in in vitro gut models have been poorly investigated. This study aimed to assess the impact of three commonly used preserving methods, compared with fresh fecal samples used as a control, on the kinetics of lumen and mucus-associated microbiota colonization in the M-ARCOL model. Feces from two healthy donors were frozen 48 h at - 80 °C with or without cryoprotectant (10% glycerol) or lyophilized with maltodextrin and trehalose prior to inoculation of four parallel bioreactors (e.g., fresh stool, raw stool stored at - 80 °C, stool stored at - 80 °C with glycerol and lyophilized stool). Microbiota composition and diversity (qPCR and 16S metabarcoding) as well as metabolic activity (gases and short chain fatty acids) were monitored throughout the fermentation process (9 days). All the preservative treatments allowed the maintaining inside the M-ARCOL of a complex and functional microbiota, but considering stabilization time of microbial profiles and activities (and not technical constraints associated with the supply of frozen material), our results highlighted 48 h freezing at - 80 °C without cryoprotectant as the most efficient method. These results will help scientists to determine the most accurate method for fecal storage prior to inoculation of in vitro gut microbiome models. KEY POINTS: • In vitro ARCOL model reproduces luminal and mucosal human microbiome. • Short-term storage of fecal sample influences microbial stabilization and activity. • 48 h freezing at - 80°C: most efficient method to preserve microbial ecosystem. • Scientific and technical requirements: influencers of preservation method.

RevDate: 2020-10-20

Sternes PR, Martin TM, Paley M, et al (2020)

HLA-A alleles including HLA-A29 affect the composition of the gut microbiome: a potential clue to the pathogenesis of birdshot retinochoroidopathy.

Scientific reports, 10(1):17636 pii:10.1038/s41598-020-74751-0.

Birdshot retinochoroidopathy occurs exclusively in individuals who are HLA-A29 positive. The mechanism to account for this association is unknown. The gut microbiome has been causally implicated in many immune-mediated diseases. We hypothesized that HLA-A29 would affect the composition of the gut microbiome, leading to a dysbiosis and immune-mediated eye disease. Fecal and intestinal biopsy samples were obtained from 107 healthy individuals from Portland, Oregon environs, 10 of whom were HLA-A29 positive, undergoing routine colonoscopy. Bacterial profiling was achieved via 16S rRNA metabarcoding. Publicly available whole meta-genome sequencing data from the Human Microbiome Project (HMP), consisting of 298 healthy controls mostly of US origin, were also interrogated. PERMANOVA and sparse partial least squares discriminant analysis (sPLSDA) demonstrated that subjects who were HLA-A29 positive differed in bacterial species composition (beta diversity) compared to HLA-A29 negative subjects in both the Portland (p = 0.019) and HMP cohorts (p = 0.0002). The Portland and HMP cohorts evidenced different subsets of bacterial species associated with HLA-A29 status, likely due to differences in the metagenomic techniques employed. The functional composition of the HMP cohort did not differ overall (p = 0.14) between HLA-A29 positive and negative subjects, although some distinct pathways such as heparan sulfate biosynthesis showed differences. As we and others have shown for various HLA alleles, the HLA allotype impacts the composition of the microbiome. We hypothesize that HLA-A29 may predispose chorioretinitis via an altered gut microbiome.

RevDate: 2020-10-19

Wenger K, Pendleton C, Xie XJ, et al (2020)

Factors associated with the counts of selected oral microorganisms in nursing home residents.

Special care in dentistry : official publication of the American Association of Hospital Dentists, the Academy of Dentistry for the Handicapped, and the American Society for Geriatric Dentistry [Epub ahead of print].

PURPOSE/AIM: To analyze potential factors associated with levels of selected oral pathogens, as well as total aerobic bacterial species, among nursing home residents.

MATERIALS AND METHODS: Nursing home residents were divided into three groups (G1 included people with teeth but no dentures, G2 included people with teeth and dentures, and G3 included people with no teeth and with dentures). All participants had microbiological samples collected from their oral cavity and dentures. Counts of total aerobic bacterial species, Porphyromonas gingivalis, Fusobacterium nucleatum, Actinomyces viscosus, Aggregatibacter actinomycetemcomitans, and Candida albicans were compared among groups using the Wilcoxon rank sum test. A multivariate analysis was also performed to control other available covariates.

RESULTS: Bivariate analysis revealed significant differences among the groups, and multivariate analysis showed that sex, the presence of natural teeth, denture wearing, oral hygiene indices, and systemic health conditions were associated with bacterial and Candida albicans log counts.

CONCLUSIONS: Presence of natural teeth and denture wearing, as well as oral hygiene, sex and systemic health conditions were associated with bacterial and Candida albicans log counts among nursing home residents.

RevDate: 2020-10-19

De Souza ALPB (2020)

Finding the hot spot: identifying immune sensitive gastrointestinal tumors.

Translational gastroenterology and hepatology, 5:48 pii:tgh-05-2019.12.11.

Although researchers have been trying to harness the immune system for over 100 years, the advent of immune checkpoint blockers (ICB) marks an era of significant clinical outcomes in various metastatic solid tumors, characterized by complete and durable responses. ICBs are monoclonal antibodies that target either of a pair of transmembrane molecules in tumors or T-cells involved in immune evasion. Currently 2 ICBs targeting the checkpoint program death 1 (PD-1), nivolumab and pembrolizumab, and one cytotoxic lymphocyte antigen-4 (CTLA-4) inhibitor (ipilimumab) are approved in gastrointestinal malignancies. We review herein the current evidence on predictive biomarkers for ICB response in gastrointestinal tumors. A review of literature based on the National Cancer Institute list of FDA-approved drugs for neoplasms and FDA-approved therapies at the FDA website was performed. An initial literature review was based on the American Association for Clinical Research meeting 2019, the American Society of Clinical Oncology meeting 2019 and the European Society of Medical Oncology 2019 proceedings. A systematic search of PubMed was performed involving MeSH browser terms such as biomarkers, immunotherapy, gastrointestinal diseases and neoplasms. When appropriate, American and British terms were used in the search. The most relevant predictor of response to ICBs is microsatellite instability (MSI) and the data is strongest for colorectal cancer. At least 3 prospective trials show evidence of PD-L1 as a predictive biomarker for ICB response in gastroesophageal malignancies. At least one prospective trial has described tumor mutational burden high (TMB-H), independent of MSI, as predictive of response in anal and biliary tract carcinomas. DNA Polymerase Epsilon (POLE) or delta (POL-D) mutations have been implicated in a subset of MSS colorectal cancer with TMB-H but this biomarker requires prospective validation. There is evolving data based on retrospective observations that gene alterations predicting acquired resistance and hyper-progression. Ongoing clinical research is assessing the role of the human microbiome and RNA-editing complex mutations as predictive biomarkers of response to ICBs. MSI has the strongest predictive power among current biomarkers for ICB response in gastrointestinal cancers. Data continue to accumulate from ongoing clinical trials and new biomarkers are emerging from pre-clinical studies, suggesting that drug combinations targeting pathways complimentary to the PD-1/PD-L1 axis inhibition will define a robust field of clinical research.

RevDate: 2020-10-19

Flores Bueso Y, Walker SP, M Tangney (2020)

Characterization of FFPE-induced bacterial DNA damage and development of a repair method.

Biology methods & protocols, 5(1):bpaa015 pii:bpaa015.

Formalin-fixed, paraffin-embedded (FFPE) specimens have huge potential as source material in the field of human microbiome research. However, the effects of FFPE processing on bacterial DNA remain uncharacterized. Any effects are relevant for microbiome studies, where DNA template is often minimal and sequences studied are not limited to one genome. As such, we aimed to both characterize this FFPE-induced bacterial DNA damage and develop strategies to reduce and repair this damage. Our analyses indicate that bacterial FFPE DNA is highly fragmented, a poor template for PCR, crosslinked and bears sequence artefacts derived predominantly from oxidative DNA damage. Two strategies to reduce this damage were devised - an optimized decrosslinking procedure reducing sequence artefacts generated by high-temperature incubation, and secondly, an in vitro reconstitution of the base excision repair pathway. As evidenced by whole genome sequencing, treatment with these strategies significantly increased fragment length, reduced the appearance of sequence artefacts and improved the sequencing readability of bacterial and mammalian FFPE DNA. This study provides a new understanding of the condition of bacterial DNA in FFPE specimens and how this impacts downstream analyses, in addition to a strategy to improve the sequencing quality of bacterial and possibly mammalian FFPE DNA.

RevDate: 2020-10-19

Kirichenko TV, Markina YV, Sukhorukov VN, et al (2020)

A Novel Insight at Atherogenesis: The Role of Microbiome.

Frontiers in cell and developmental biology, 8:586189.

There is an important task of current medicine to identify mechanisms and new markers of subclinical atherosclerosis in order to develop early targets for the diagnosis and treatment of this disease, since it causes such widespread diseases as myocardial infarction, stroke, sudden death, and other common reasons of disability and mortality in developed countries. In recent years, studies of the human microbiome in different fields of medicine have become increasingly popular; there is evidence from numerous studies of the significant contribution of microbiome in different steps of atherogenesis. This review attempted to determine the current status of the databases PubMed and Scopus (until May, 2020) to highlight current ideas on the potential role of microbiome and its metabolites in atherosclerosis development, its mechanisms of action in lipids metabolism, endothelial dysfunction, inflammatory pathways, and mitochondrial dysfunction. Results of clinical studies elucidating the relationship of microbiome with subclinical atherosclerosis and cardiovascular disease considered in this article demonstrate strong association of microbiome composition and its metabolites with atherosclerosis and cardiovascular disease. Data on microbiome impact in atherogenesis open a wide perspective to develop new diagnostic and therapeutic approaches, but further comprehensive studies are necessary.

RevDate: 2020-10-19

Rackaityte E, SV Lynch (2020)

The human microbiome in the 21st century.

Nature communications, 11(1):5256 pii:10.1038/s41467-020-18983-8.

RevDate: 2020-10-19

Castañeda S, Muñoz M, Villamizar X, et al (2020)

Microbiota characterization in Blastocystis-colonized and Blastocystis-free school-age children from Colombia.

Parasites & vectors, 13(1):521 pii:10.1186/s13071-020-04392-9.

BACKGROUND: Blastocystis is a protist that lives in the intestinal tract of a variety of hosts, including humans. It is still unclear how Blastocystis causes disease, which presents an ongoing challenge for researchers. Despite the controversial findings on the association between Blastocystis and clinical digestive manifestations, there is currently no consensus as to whether this protozoan actually behaves as a pathogen in humans. Furthermore, the relationship between Blastocystis and the intestinal microbiota composition is not yet clear. For that reason, the aim of this study was to identify if colonization by Blastocystis is related to changes in the diversity and relative abundance of bacterial communities, compared with those of Blastocystis-free individuals in a group of Colombian children.

METHODS: We took stool samples from 57 school-aged children attending a daycare institution in Popayán (Southwest Colombia). Whole DNA was extracted and examined by 16S-rRNA amplicon-based sequencing. Blastocystis was detected by real time PCR and other intestinal parasites were detected by microscopy. We evaluated if Blastocystis was associated with host variables and the diversity and abundance of microbial communities.

RESULTS: The composition of the intestinal bacterial community was not significantly different between Blastocystis-free and Blastocystis-colonized children. Despite this, we observed a higher microbial richness in the intestines of children colonized by Blastocystis, which could, therefore, be considered a benefit to intestinal health. The phylum Firmicutes was the predominant taxonomic unit in both groups analyzed. In Blastocystis-free individuals, there was a higher proportion of Bacteroidetes; similarly, in children colonized by Blastocystis, there was a higher relative abundance of the phylum Proteobacteria; however, no statistically significant differences were found between the comparison groups.

CONCLUSIONS: The presence of Blastocystis showed a decrease in Bacteroides, and an increase in the relative abundance of the genus Faecalibacterium. It was also evident that the presence of Blastocystis was unrelated to dysbiosis at the intestinal level; on the contrary, its presence did not show statistically differences in the intestinal microbiota composition. Nevertheless, we believe that Blastocystis plays a role in the ecology of the intestinal microbiota through its interaction with other microbial components.

RevDate: 2020-10-16

Tan HY, YC Toh (2020)

What can microfluidics do for human microbiome research?.

Biomicrofluidics, 14(5):051303 pii:5.0012185.

Dysregulation of the human microbiome has been linked to various disease states, which has galvanized the efforts to modulate human health through microbiomes. Currently, human microbiome research is going through several phases to identify the constituent components of the microbiome, associate microbiome changes with physiological and pathological states, understand causative relationships, and finally translate this knowledge into therapeutics and diagnostics. The convergence of microfluidic technologies with molecular and cell profiling, microbiology, and tissue engineering can potentially be applied to these different phases of microbiome research to overcome the existing challenges faced by conventional approaches. The goal of this paper is to discuss and highlight the opportunities of applying different microfluidic technologies to specific areas of microbiome research as well as unique challenges that microfluidics must overcome when working with microbiome-relevant biological materials, e.g., micro-organisms, host tissues, and fluids. We will discuss the applicability of integrated microfluidic systems for processing biological samples for genomic sequencing analyses. For functional analysis of the microbiota, we will cover state-of-the-art microfluidic devices for microbiota cultivation and functional measurements. Finally, we highlight the use of organs-on-chips to model various microbiome-host tissue interactions. We envision that microfluidic technologies may hold great promise in advancing the knowledge on the interplay between microbiome and human health, as well as its eventual translation into microbiome-based diagnostics and therapeutics.

RevDate: 2020-10-15

Eller CH, RT Raines (2020)

Antimicrobial Synergy of a Ribonuclease and a Peptide Secreted by Human Cells.

ACS infectious diseases [Epub ahead of print].

LL-37 is a secretory peptide that has antimicrobial activity. Ribonuclease 1 (RNase 1) is a secretory enzyme that is not cytotoxic. We find that human LL-37 and human RNase 1 can act synergistically to kill Gram-negative bacterial cells. In the presence of nontoxic concentrations of LL-37, RNase 1 is toxic to Escherichia coli cells at picomolar levels. Using wild-type RNase 1 and an inactive variant labeled with a fluorophore, we observe the adherence of RNase 1 to E. coli cells and its cellular entry in the presence of LL-37. These data suggest a natural means of modulating the human microbiome via the cooperation of an endogenous peptide (37 residues) and small enzyme (128 residues).

RevDate: 2020-10-13

Reichhardt MP, Messing M, Andersson S, et al (2020)

Intestinal SALSA/dmbt1 levels are decreased in prematurely born infants.

Scandinavian journal of immunology [Epub ahead of print].

The first months of life represent a crucial time period for an infant. Alongside establishing the early microbiome, the mucosal immunological homeostasis is being developed. Both processes may be perturbed in prematurely born infants. The glycoprotein SALSA plays a role in mucosal inflammation and microbial clearance. It is one of the most abundant molecules on the intestinal mucosal surfaces in early life. SALSA binds to many types of microbes and host defense molecules like IgA, C1q and collectin molecules. We here describe the development in fecal SALSA levels during the first three months of life. During these 90 days the median SALSA level in full-term babies decreased from 1100 μg/ml (range 49 - 17000 μg/ml) to 450 μg/ml (range 33 - 1000 μg/ml). Lower levels of SALSA were observed in prematurely born infants in the same time period. Our novel observation thus indicates an impact of prematurity on an important component of the infant intestinal immune system. Changes in SALSA in early life may have an effect on the early establishment of the human microbiome.

RevDate: 2020-10-13

Kenney T, Gao J, H Gu (2020)

Application of OU processes to modelling temporal dynamics of the human microbiome, and calculating optimal sampling schemes.

BMC bioinformatics, 21(1):450 pii:10.1186/s12859-020-03747-4.

BACKGROUND: The vast majority of microbiome research so far has focused on the structure of the microbiome at a single time-point. There have been several studies that measure the microbiome from a particular environment over time. A few models have been developed by extending time series models to accomodate specific features in microbiome data to address questions of stability and interactions of the microbime time series. Most research has observed the stability and mean reversion for some microbiomes. However, little has been done to study the mean reversion rates of these stable microbes and how sampling frequencies are related to such conclusions. In this paper, we begin to rectify this situation. We analyse two widely studied microbial time series data sets on four healthy individuals. We choose to study healthy individuals because we are interested in the baseline temporal dynamics of the microbiome.

RESULTS: For this analysis, we focus on the temporal dynamics of individual genera, absorbing all interactions in a stochastic term. We use a simple stochastic differential equation model to assess the following three questions. (1) Does the microbiome exhibit temporal continuity? (2) Does the microbiome have a stable state? (3) To better understand the temporal dynamics, how frequently should data be sampled in future studies? We find that a simple Ornstein-Uhlenbeck model which incorporates both temporal continuity and reversion to a stable state fits the data for almost every genus better than a Brownian motion model that contains only temporal continuity. The Ornstein-Uhlenbeck model also fits the data better than modelling separate time points as independent. Under the Ornstein-Uhlenbeck model, we calculate the variance of the estimated mean reversion rate (the speed with which each genus returns to its stable state). Based on this calculation, we are able to determine the optimal sample schemes for studying temporal dynamics.

CONCLUSIONS: There is evidence of temporal continuity for most genera; there is clear evidence of a stable state; and the optimal sampling frequency for studying temporal dynamics is in the range of one sample every 0.8-3.2 days.

RevDate: 2020-10-13

Gao H, Sun T, Yang F, et al (2020)

The Pathogenic Effects of Fusobacterium nucleatum on the Proliferation, Osteogenic Differentiation, and Transcriptome of Osteoblasts.

Frontiers in cell and developmental biology, 8:807.

As one of the most common oral diseases, periodontitis is closely correlated with tooth loss in middle-aged and elderly people. Fusobacterium nucleatum (F. nucleatum) contributes to periodontitis, but the evidence in alveolar bone loss is still unclear. In this study, cytological experiments and transcriptome analyses were performed to characterize the biological process abnormalities and the molecular changes of F. nucleatum-stimulated osteoblasts. F. nucleatum could inhibit cell proliferation, promote cell apoptosis, and elevate pro-inflammatory cytokine production of osteoblasts, and it also inhibited osteoblast differentiation and mineralized nodule formation and decreased the expression of osteogenetic genes and proteins. Whole-transcriptome analyses identified a total of 235 transcripts that were differentially expressed in all six time points, most of which were inflammation-related genes. The genes, Ccl2, Ccl20, Csf1, Cx3cl1, Cxcl1, Cxcl3, Il6, Birc3, Map3k8, Nos2, Nfkb2, Tnfrsf1b, and Vcam1, played core roles in a PPI network, and interacted closely with other ones in the infection. In addition, 133 osteogenesis-related differential expression genes (DEGs) were time-serially dynamically changed in a short time-series expression miner (STEM) analysis, which were enriched in multiple cancer-related pathways. The core dynamic DEGs (Mnda, Cyp1b1, Comp, Phex, Mmp3, Tnfrsf1b, Fbln5, and Nfkb2) had been reported to be closely related to the development and metastasis in tumor and cancer progress. This study is the first to evaluate the long-term interaction of F. nucleatum on osteoblasts, which might increase the risk of cell carcinogenesis of normal osteoblasts, and provides new insight into the pathogenesis of bacterial-induced bone destruction.

RevDate: 2020-10-12

Vernocchi P, Marini F, Capuani G, et al (2020)

Fused Omics Data Models Reveal Gut Microbiome Signatures Specific of Inactive Stage of Juvenile Idiopathic Arthritis in Pediatric Patients.

Microorganisms, 8(10): pii:microorganisms8101540.

Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in children. Herein, we evaluated the relationship between the gut microbiome (GM) and disease phenotype by an integrated omics fused approach. In a multicenter, observational cohort study, stools from Italian JIA patients were collected at baseline, active, and inactive disease stages, and their GM compared to healthy controls (CTRLs). The microbiota metabolome was analyzed to detect volatile- and non-volatile organic compounds (VOCs); the data were fused with operational taxonomic units (OTUs) from 16S RNA targeted-metagenomics and classified by chemometric models. Non-VOCs did not characterize JIA patients nor JIA activity stages compared to CTRLs. The core of VOCs, (Ethanol, Methyl-isobutyl-ketone, 2,6-Dimethyl-4-heptanone and Phenol) characterized patients at baseline and inactive disease stages, while the OTUs represented by Ruminococcaceae, Lachnospiraceae and Clostridiacea discriminated between JIA inactive stage and CTRLs. No differences were highlighted amongst JIA activity stages. Finally, the fused data discriminated inactive and baseline stages versus CTRLs, based on the contribution of the invariant core of VOCs while Ruminococcaceae concurred for the inactive stage versus CTRLs comparison. In conclusion, the GM signatures enabled to distinguish the inactive disease stage from CTRLs.

RevDate: 2020-10-08

Shi HL, Lan YH, Hu ZC, et al (2020)

Microecology research: a new target for the prevention of asthma.

Chinese medical journal [Epub ahead of print].

The incidence and prevalence of asthma have increased remarkably in recent years. There are lots of factors contributing to the occurrence and development of asthma. With the improvement of sequencing technology, it has been found that the microbiome plays an important role in the formation of asthma in early life. The roles of the microbial environment and human microbiome in the occurrence and development of asthma have attracted more and more attention. The environmental microbiome influences the occurrence of asthma by shaping the human microbiome. The specific mechanism may be related to the immune regulation of Toll-like receptors and T cells (special Tregs). Intestinal microbiome is formed and changed by regulating diet and lifestyle in early life, which may affect the development and maturation of the pulmonary immune system through the intestinal-pulmonary axis. It is well-recognized that both environmental microbiomes and human microbiomes can influence the onset of asthma. This review aims to summarize the recent advances in the research of microbiome, its relationship with asthma, and the possible mechanism of the microbiome in the occurrence and development of asthma. The research of the microbial environment and human microbiome may provide a new target for the prevention of asthma in children who have high-risk factors to allergy. However, further study of "when and how" to regulate microbiome is still needed.

RevDate: 2020-10-07

Kozik AJ (2020)

mSphere of Influence: Frameshift-a Vision for Human Microbiome Research.

mSphere, 5(5):.

Ariangela J. Kozik studies the respiratory microbiome as it relates to asthma. In this mSphere of Influence article, she reflects on how two papers, "Time's up to adopt a biopsychosocial model to address racial and ethnic disparities in asthma outcomes" (E. C. Matsui, A. S. Adamson, and R. D. Peng, Allergy Clin Immunol 143:2024-2025, 2019, and "Health disparities and the microbiome" (K. Findley, D. R. Williams, E. A. Grice, and V. L. Bonham, Trends Microbiol 24:847-850, 2016,, shape her approach to human microbiome research.

RevDate: 2020-10-06

Santacroce L, Charitos IA, Ballini A, et al (2020)

The Human Respiratory System and its Microbiome at a Glimpse.

Biology, 9(10): pii:biology9100318.

The recent COVID-19 pandemic promoted efforts to better understand the organization of the respiratory microbiome and its evolution from birth to adulthood and how it interacts with external pathogens and the host immune system. This review aims to deepen understanding of the essential physiological functions of the resident microbiome of the respiratory system on human health and diseases. First, the general characteristics of the normal microbiota in the different anatomical sites of the airways have been reported in relation to some factors such as the effect of age, diet and others on its composition and stability. Second, we analyze in detail the functions and composition and the correct functionality of the microbiome in the light of current knowledge. Several studies suggest the importance of preserving the micro-ecosystem of commensal, symbiotic and pathogenic microbes of the respiratory system, and, more recently, its relationship with the intestinal microbiome, and how it also leads to the maintenance of human health, has become better understood.

RevDate: 2020-10-06

Durack J, CT Christophersen (2020)

Human Respiratory and Gut Microbiomes-Do They Really Contribute to Respiratory Health?.

Frontiers in pediatrics, 8:528.

Human gastrointestinal and respiratory tracts are colonized by diverse polymicrobial communities shortly after birth, which are continuously molded by environmental exposure. The development of the resident microbiota in early life is a critical factor in the maturation of a healthy immune system. Disturbances to the intricate relationship between environmental exposure and maturation of the infant microbiome have been increasingly identified as a potential contributor to a range of childhood diseases. This review details recent evidence that implicates the contribution of gut and airway microbiome to pediatric respiratory health.

RevDate: 2020-10-05

Jacobson DK, Honap TP, Monroe C, et al (2020)

Functional diversity of microbial ecologies estimated from ancient human coprolites and dental calculus.

Philosophical transactions of the Royal Society of London. Series B, Biological sciences, 375(1812):20190586.

Human microbiome studies are increasingly incorporating macroecological approaches, such as community assembly, network analysis and functional redundancy to more fully characterize the microbiome. Such analyses have not been applied to ancient human microbiomes, preventing insights into human microbiome evolution. We address this issue by analysing published ancient microbiome datasets: coprolites from Rio Zape (n = 7; 700 CE Mexico) and historic dental calculus (n = 44; 1770-1855 CE, UK), as well as two novel dental calculus datasets: Maya (n = 7; 170 BCE-885 CE, Belize) and Nuragic Sardinians (n = 11; 1400-850 BCE, Italy). Periodontitis-associated bacteria (Treponema denticola, Fusobacterium nucleatum and Eubacterium saphenum) were identified as keystone taxa in the dental calculus datasets. Coprolite keystone taxa included known short-chain fatty acid producers (Eubacterium biforme, Phascolarctobacterium succinatutens) and potentially disease-associated bacteria (Escherichia, Brachyspira). Overlap in ecological profiles between ancient and modern microbiomes was indicated by similarity in functional response diversity profiles between contemporary hunter-gatherers and ancient coprolites, as well as parallels between ancient Maya, historic UK, and modern Spanish dental calculus; however, the ancient Nuragic dental calculus shows a distinct ecological structure. We detected key ecological signatures from ancient microbiome data, paving the way to expand understanding of human microbiome evolution. This article is part of the theme issue 'Insights into health and disease from ancient biomolecules'.

RevDate: 2020-10-05

Schnorr SL (2020)

The soil in our microbial DNA informs about environmental interfaces across host and subsistence modalities.

Philosophical transactions of the Royal Society of London. Series B, Biological sciences, 375(1812):20190577.

In this study, I use microbiome datasets from global soil samples and diverse hosts to learn whether soil microbial taxa are found in host microbiomes, and whether these observations fit the narrative that environmental interaction influences human microbiomes. A major motivation for conducting host-associated microbiome research is to contribute towards understanding how the environment may influence host physiology. The microbial molecular network is considered a key vector by which environmental traits may be transmitted to the host. Research on human evolution seeks evidence that can inform about the living experiences of human ancestors. This objective is substantially enhanced by recent work on ancient biomolecules from preserved microbial tissues, such as dental calculus, faecal sediments and whole coprolites. A challenge yet is to distinguish authentic biomolecules from environmental contaminants deposited contemporaneously, primarily from soil. However, we do not have sound expectations about the soil microbial elements arriving to host-associated microbiomes in a modern context. One assumption in human microbiome research is that proximity to the natural environment should affect biodiversity or impart genetic elements. I present evidence supporting the assumption that environmental soil taxa are found among host-associated gut taxa, which can recapitulate the surrounding host habitat ecotype. Soil taxa found in gut microbiomes relate to a set of universal 'core' taxa for all soil ecotypes, demonstrating that widespread host organisms may experience a consistent pattern of external environmental cues, perhaps critical for development. Observed differentiation of soil feature diversity, abundance and composition among human communities, great apes and invertebrate hosts also indicates that lifestyle patterns are inferable from an environmental signal that is retrievable from gut microbiome amplicon data. This article is part of the theme issue 'Insights into health and disease from ancient biomolecules'.

RevDate: 2020-10-13

Wan X, Hendrix H, Skurnik M, et al (2020)

Phage-based target discovery and its exploitation towards novel antibacterial molecules.

Current opinion in biotechnology, 68:1-7 pii:S0958-1669(20)30122-1 [Epub ahead of print].

The deeply intertwined evolutionary history between bacteriophages and bacteria has endowed phages with highly specific mechanisms to hijack bacterial cell metabolism for their propagation. Here, we present a comprehensive, phage-driven strategy to reveal novel antibacterial targets by the exploitation of phage-bacteria interactions. This strategy will enable the design of small molecules, which mimic the inhibitory phage proteins, and allow the subsequent hit-to-lead development of these antimicrobial compounds. This proposed small molecule approach is distinct from phage therapy and phage enzyme-based antimicrobials and may produce a more sustainable generation of new antibiotics that exploit novel bacterial targets and act in a pathogen-specific manner.

RevDate: 2020-10-13

Bhar S, Edelmann MJ, MK Jones (2020)

Characterization and proteomic analysis of outer membrane vesicles from a commensal microbe, Enterobacter cloacae.

Journal of proteomics, 231:103994 pii:S1874-3919(20)30362-6 [Epub ahead of print].

Outer membrane vesicles (OMVs) are membrane-enclosed spherical entities released by gram-negative bacteria and are important for bacterial survival under stress conditions. There have been numerous studies on OMVs released by gram-negative pathogenic bacteria, but an understanding of the functions and characteristics of the OMVs produced by commensal microbes is still lacking. Enterobacter cloacae is a gram-negative commensal bacterium present in the human gut microbiome, but this organism can also function as an opportunistic pathogen. Understanding the OMV-mediated communication route between bacteria-bacteria or bacteria-host is essential for the determination of the biological functions of the commensal bacterium in the gut and delineating between benign and virulent characteristics. In this study, we have described a proteome of E. cloacae OMVs, which are membrane vesicles in a size range of 20-300 nm. Proteomic analysis showed the presence of membrane-bound proteins, including transporters, receptors, signaling molecules, and protein channels. The physical and proteomic analyses also indicate this bacterium uses two mechanisms for OMV production. This study is one of the few existing descriptions of the proteomic profile of OMVs generated by a commensal Proteobacteria, and the first report of OMVs produced by E. cloacae. SIGNIFICANCE: This study prioritizes the importance of understanding the vesicular proteome of the human commensal bacterium, Enterobacter cloacae. We demonstrate for the first time that the gram-negative bacterium E. cloacae ATCC 13047 produces outer membrane vesicles (OMVs). The proteomic analysis showed enrichment of membrane-bound proteins in these vesicles. Understanding the cargo proteins of OMVs will help in exploring the physiological and functional role of these vesicles in the human microbiome and how they assist in the conversion of a bacterium from commensal to pathogen under certain conditions. While EM images reveal vesicles budding from the bacterial surface, the presence of cytoplasmic proteins and genomic DNA within the OMVs indicate that explosive cell lysis is an additional mechanism of biogenesis for these OMVs along with outer membrane blebbing. This research encourages future work on characterizing membrane vesicles produced by commensal bacterial and investigating their role in cell to cell communication.

RevDate: 2020-10-13

Rajeev R, Prathiviraj R, Kiran GS, et al (2020)

Zoonotic evolution and implications of microbiome in viral transmission and infection.

Virus research, 290:198175 pii:S0168-1702(20)31082-0 [Epub ahead of print].

The outbreak and spread of new strains of coronavirus (SARS-CoV-2) remain a global threat with increasing cases in affected countries. The evolutionary tree of SARS-CoV-2 revealed that Porcine Reproductive and Respiratory Syndrome virus 2, which belongs to the Beta arterivirus genus from the Arteriviridae family is possibly the most ancient ancestral origin of SARS-CoV-2 and other Coronaviridae. This review focuses on phylogenomic distribution and evolutionary lineage of zoonotic viral cross-species transmission of the Coronaviridae family and the implications of bat microbiome in zoonotic viral transmission and infection. The review also casts light on the role of the human microbiome in predicting and controlling viral infections. The significance of microbiome-mediated interventions in the treatment of viral infections is also discussed. Finally, the importance of synthetic viruses in the study of viral evolution and transmission is highlighted.

RevDate: 2020-10-02

Korpela K, Helve O, Kolho KL, et al (2020)

Maternal Fecal Microbiota Transplantation in Cesarean-Born Infants Rapidly Restores Normal Gut Microbial Development: A Proof-of-Concept Study.

Cell pii:S0092-8674(20)31089-8 [Epub ahead of print].

Infants born by vaginal delivery are colonized with maternal fecal microbes. Cesarean section (CS) birth disturbs mother-to-neonate transmission. In this study (NCT03568734), we evaluated whether disturbed intestinal microbiota development could be restored in term CS-born infants by postnatal, orally delivered fecal microbiota transplantation (FMT). We recruited 17 mothers, of whom seven were selected after careful screening. Their infants received a diluted fecal sample from their own mothers, taken 3 weeks prior to delivery. All seven infants had an uneventful clinical course during the 3-month follow-up and showed no adverse effects. The temporal development of the fecal microbiota composition of FMT-treated CS-born infants no longer resembled that of untreated CS-born infants but showed significant similarity to that of vaginally born infants. This proof-of-concept study demonstrates that the intestinal microbiota of CS-born infants can be restored postnatally by maternal FMT. However, this should only be done after careful clinical and microbiological screening.

RevDate: 2020-10-13

Shetty SA, Boeren S, Bui TPN, et al (2020)

Unravelling lactate-acetate and sugar conversion into butyrate by intestinal Anaerobutyricum and Anaerostipes species by comparative proteogenomics.

Environmental microbiology [Epub ahead of print].

The d- and l-forms of lactate are important fermentation metabolites produced by intestinal bacteria but are found to negatively affect mucosal barrier function and human health. Both enantiomers of lactate can be converted with acetate into the presumed beneficial butyrate by a phylogenetically related group of anaerobes, including Anaerobutyricum and Anaerostipes spp. This is a low energy yielding process with a partially unknown pathway in Anaerobutyricum and Anaerostipes spp. and hence, we sought to address this via a comparative genomics, proteomics and physiology approach. We compared growth of Anaerobutyricum soehngenii on lactate with that on sucrose and sorbitol. Comparative proteomics revealed complete pathway of butyrate formation from sucrose, sorbitol and lactate. Notably, a gene cluster, lctABCDEF was abundantly expressed when grown on lactate. This gene cluster encodes a lactate dehydrogenase (lctD), electron transport proteins A and B (lctCB), nickel-dependent racemase (lctE), lactate permease (lctF) and short-chain acyl-CoA dehydrogenase (lctG). Investigation of available genomes of intestinal bacteria revealed this new gene cluster to be highly conserved in only Anaerobutyricum and Anaerostipes spp. Present study demonstrates that A. soehngenii and several related Anaerobutyricum and Anaerostipes spp. are highly adapted for a lifestyle involving lactate plus acetate utilization in the human intestinal tract.

RevDate: 2020-10-01

Ottman N, Barrientos-Somarribas M, Fyhrquist N, et al (2020)

Microbial and transcriptional differences elucidate atopic dermatitis heterogeneity across skin sites.

Allergy [Epub ahead of print].

It is well established that different sites in healthy human skin are colonized by distinct microbial communities due to different physiological conditions. However, few studies have explored microbial heterogeneity between skin sites in diseased skin, such as atopic dermatitis (AD) lesions. To address this issue, we carried out deep analysis of the microbiome and transcriptome in the skin of a large cohort of AD patients and healthy volunteers, comparing two physiologically different sites: upper back and posterior thigh. Microbiome samples and biopsies were obtained from both lesional and non-lesional skin to identify changes related to the disease process. Transcriptome analysis revealed distinct disease-related gene expression profiles depending on anatomical location, with keratinization dominating the transcriptomic signatures in posterior thigh, and lipid metabolism in the upper back. Moreover, we show that relative abundance of Staphylococcus aureus is associated with disease severity in the posterior thigh, but not in the upper back. Our results suggest that AD may select for similar microbes in different anatomical locations - an 'AD-like microbiome', but distinct microbial dynamics can still be observed when comparing posterior thigh to upper back. This study highlights the importance of considering the variability across skin sites when studying the development of skin inflammation.

RevDate: 2020-10-13
CmpDate: 2020-10-13

Johnson MDL (2020)

mSphere Highlights Black In Microbiology Week.

mSphere, 5(5):.

The inaugural Black In Microbiology Week (#BlackInMicro) is 28 September 2020 through 4 October 2020. Its mission is to "showcase the presence and accomplishments of Black microbiologists from around the globe, connect Black microbiologists with one another and foster a sense of community among them, and provide a forum for the discussion of racial disparities in microbiology and its subfields." Participation in this event will happen primarily over Twitter through the hashtag #BlackInMicro and over Zoom through registration on the website An additional mission of Black In Microbiology Week is to amplify black scientists. Today, mSphere does this by presenting two mSphere of Influence commentaries from Black In Microbiology co-lead organizers Ariangela J. Kozik ("mSphere of Influence: frameshift-a vision for human microbiome research" [mSphere 5:e00944-20, 2020,]) and Kishana Taylor ("mSphere of Influence: that's racist-COVID-19, biological determinism, and the limits of hypotheses" [mSphere 5:e00945-20, 2020,]).

RevDate: 2020-10-03

Soverini M, Rampelli S, Turroni S, et al (2020)

Do the human gut metagenomic species possess the minimal set of core functionalities necessary for life?.

BMC genomics, 21(1):678.

BACKGROUND: Advances in bioinformatics recently allowed for the recovery of 'metagenomes assembled genomes' from human microbiome studies carried on with shotgun sequencing techniques. Such approach is used as a mean to discover new unclassified metagenomic species, putative biological entities having distinct metabolic traits.

RESULTS: In the present analysis we compare 400 genomes from isolates available on NCBI database and 10,000 human gut metagenomic species, screening all of them for the presence of a minimal set of core functionalities necessary, but not sufficient, for life. As a result, the metagenome-assembled genomes resulted systematically depleted in genes encoding for essential functions apparently needed to support autonomous bacterial life.

CONCLUSIONS: The relevant degree of lacking core functionalities that we observed in metagenome-assembled genomes raises some concerns about the effective completeness of metagenome-assembled genomes, suggesting caution in extrapolating biological information about their metabolic propensity and ecology in a complex environment like the human gastrointestinal tract.

RevDate: 2020-09-30

Lang S, Brandau S, Marchesi JR, et al (2020)

[The microbiome in head and neck tumors-initial findings and outlook].

HNO pii:10.1007/s00106-020-00950-w [Epub ahead of print].

Technical progress in molecular biology has allowed for a more detailed analysis of the composition of the human microbiome in recent years. Inter- and intraindividual differences in microbiome composition have been demonstrated, which in part correlate with the occurrence of certain diseases. For some of the so-called oncomicrobes, a direct relationship between their effect on the host organism and carcinogenesis has been demonstrated, predominantly for gastrointestinal cancers. Initial results for head and neck cancer show inter- and intraindividual differences in the local microbiota of the tumor environment, with certain bacterial strains over- or underrepresented. Our results confirm these findings, e.g., by showing a relative abundance of fusobacteria in tumor tissue while streptococci were relatively reduced. Currently available results show a high degree of inter- and intraindividual variation, thus requiring larger patient cohorts for functional analyses.

RevDate: 2020-10-03

Schmidt V, Enav H, Spector TD, et al (2020)

Strain-Level Analysis of Bifidobacterium spp. from Gut Microbiomes of Adults with Differing Lactase Persistence Genotypes.

mSystems, 5(5):.

One of the strongest associations between human genetics and the gut microbiome is a greater relative abundance of Bifidobacterium in adults with lactase gene (LCT) single nucleotide polymorphisms (SNPs) associated with lactase nonpersistence (GG genotypes), versus lactase persistence (AA/AG genotypes). To gain a finer-grained phylogenetic resolution of this association, we interrogated 1,680 16S rRNA libraries and 245 metagenomes from gut microbiomes of adults with various lactase persistence genotypes. We further employed a novel genome-capture-based enrichment of Bifidobacterium DNA from a subset of these metagenomes, including monozygotic (MZ) twin pairs, each sampled 2 or 3 times. B. adolescentis and B. longum were the most abundant Bifidobacterium species regardless of host LCT genotype. LCT genotypes could not be discriminated based on relative abundances of Bifidobacterium species or Bifidobacterium community structure. Three distinct metagenomic analysis methods of Bifidobacterium-enriched DNA revealed intraindividual temporal stability of B. longum, B. adolescentis, and B. bifidum strains against the background of a changeable microbiome. Two of our three methods also observed greater strain sharing within MZ twin pairs than within unrelated individuals for B. adolescentis, while no method revealed an effect of host LCT genotype on Bifidobacterium strain composition. Our results support a "rising tide lifts all boats" model for the dominant bifidobacteria in the adult gut: their higher abundance in lactase-nonpersistent than in lactase-persistent individuals results from an expansion at the genus level. Bifidobacterium species are known to be transmitted from mother to child and stable within individuals in infancy and childhood: our results extend this stability into adulthood.IMPORTANCE When humans domesticated animals, some adapted genetically to digest milk into adulthood (lactase persistence). The gut microbiomes of people with lactase-persistent genotypes (AA or AG) differ from those with lactase-nonpersistent genotypes (GG) by containing fewer bacteria belonging to the bifidobacteria, a group which contains beneficial species. Here, we asked if the gut microbiomes of adults with GG and AA/AG genotypes differ in the species of bifidobacteria present. In particular, we used a novel technique which allowed us to compare bifidobacteria in adults at the strain level, without the traditional need for culturing. Our results show that the GG genotype enhances the abundance of bifidobacteria regardless of species. We also noted that a person's specific strains are recoverable several years later, and twins can share the same ones. Given that bifidobacteria are inherited from mother to child, strain stability over time in adulthood suggests long-term, multigenerational inheritance.

RevDate: 2020-10-13

Ervin SM, Simpson JB, Gibbs ME, et al (2020)

Structural Insights into Endobiotic Reactivation by Human Gut Microbiome-Encoded Sulfatases.

Biochemistry, 59(40):3939-3950.

Phase II drug metabolism inactivates xenobiotics and endobiotics through the addition of either a glucuronic acid or sulfate moiety prior to excretion, often via the gastrointestinal tract. While the human gut microbial β-glucuronidase enzymes that reactivate glucuronide conjugates in the intestines are becoming well characterized and even controlled by targeted inhibitors, the sulfatases encoded by the human gut microbiome have not been comprehensively examined. Gut microbial sulfatases are poised to reactivate xenobiotics and endobiotics, which are then capable of undergoing enterohepatic recirculation or exerting local effects on the gut epithelium. Here, using protein structure-guided methods, we identify 728 distinct microbiome-encoded sulfatase proteins from the 4.8 million unique proteins present in the Human Microbiome Project Stool Sample database and 1766 gut microbial sulfatases from the 9.9 million sequences in the Integrated Gene Catalogue. We purify a representative set of these sulfatases, elucidate crystal structures, and pinpoint unique structural motifs essential to endobiotic sulfate processing. Gut microbial sulfatases differentially process sulfated forms of the neurotransmitters serotonin and dopamine, and the hormones melatonin, estrone, dehydroepiandrosterone, and thyroxine in a manner dependent both on variabilities in active site architecture and on markedly distinct oligomeric states. Taken together, these data provide initial insights into the structural and functional diversity of gut microbial sulfatases, providing a path toward defining the roles these enzymes play in health and disease.

RevDate: 2020-10-02

Ternák G, Berényi K, Sümegi A, et al (2020)

Antibiotic Consumption Patterns in European Countries May Be Associated with the Incidence of Major Carcinomas.

Antibiotics (Basel, Switzerland), 9(10): pii:antibiotics9100643.

The possible role of the altered intestinal microbiome in the development of malignancies has been raised recently in several publications. Among external factors, antibiotics are considered to be the most important agent capable of producing dysbiosis in the gut flora, either temporally or permanently. The human microbiome has several beneficial effects in terms of maintaining appropriate human health, but its alteration has been implicated in the development of many illnesses. Our basic aim was to explore a possible relationship between the consumption of different antibiotic classes and the incidence of the most common cancer types (male, female) in European countries. A database of the average, yearly antibiotic consumption (1997-2018) has been developed and the consumption figures were compared to the eight, most frequent cancer incidence calculated for 2018 in 30 European countries. Pearson correlation has indicated different degrees of positive (supportive) and negative (inhibitor) significant associations between antibiotic consumption figures and cancer prevalence. It has been observed that certain antibiotic classes with positive correlation probably augment the incidence of certain cancer types, while others, with negative correlation, may show some inhibitory effect. The relatively higher or lower consumption pattern of different classes of antibiotics could be related to certain cancer prevalence figures in different European countries. Our results indicated that countries with relatively high consumption of narrow-spectrum penicillin (J01CE, J01CF) and tetracycline (J01A), like certain Scandinavian countries, showed a higher incidence of female colorectal cancer, female lung cancer, melanoma, breast, prostate and uterus corpus cancer. Countries with relatively higher consumption of broad-spectrum penicillin (J01CA, J01CR) and some broad-spectrum antibiotics (J01D, J01F, J01M), like Greece, Hungary, Slovakia, France, etc. showed a higher incidence rate of male lung cancer and male bladder cancer. The higher incidence rate of different cancer types showed association with the higher consumption of antibiotics with "augmenting" properties and with less consumption of antibiotics with "inhibitory" properties.

RevDate: 2020-10-02

Quagliariello A, Del Chierico F, Reddel S, et al (2020)

Fecal Microbiota Transplant in Two Ulcerative Colitis Pediatric Cases: Gut Microbiota and Clinical Course Correlations.

Microorganisms, 8(10): pii:microorganisms8101486.

Fecal microbiota transplantation (FMT) is a promising strategy in the management of inflammatory bowel disease (IBD). The clinical effects of this practice are still largely unknown and unpredictable. In this study, two children affected by mild and moderate ulcerative colitis (UC), were pre- and post-FMT monitored for clinical conditions and gut bacterial ecology. Microbiota profiling relied on receipts' time-point profiles, donors and control cohorts' baseline descriptions. After FMT, the improvement of clinical conditions was recorded for both patients. After 12 months, the mild UC patient was in clinical remission, while the moderate UC patient, after 12 weeks, had a clinical worsening. Ecological analyses highlighted an increase in microbiota richness and phylogenetic distance after FMT. This increase was mainly due to Collinsella aerofaciens and Eubacterium biforme, inherited by respective donors. Moreover, a decrease of Proteus and Blautia producta, and the increment of Parabacteroides, Mogibacteriaceae, Bacteroides eggerthi, Bacteroides plebeius, Ruminococcus bromii, and BBacteroidesovatus were associated with remission of the patient's condition. FMT results in a long-term response in mild UC, while in the moderate form there is probably need for multiple FMT administrations. FMT leads to a decrease in potential pathogens and an increase in microorganisms correlated to remission status.

RevDate: 2020-10-01

Ha CWY, Martin A, Sepich-Poore GD, et al (2020)

Translocation of Viable Gut Microbiota to Mesenteric Adipose Drives Formation of Creeping Fat in Humans.

Cell [Epub ahead of print].

A mysterious feature of Crohn's disease (CD) is the extra-intestinal manifestation of "creeping fat" (CrF), defined as expansion of mesenteric adipose tissue around the inflamed and fibrotic intestine. In the current study, we explore whether microbial translocation in CD serves as a central cue for CrF development. We discovered a subset of mucosal-associated gut bacteria that consistently translocated and remained viable in CrF in CD ileal surgical resections, and identified Clostridium innocuum as a signature of this consortium with strain variation between mucosal and adipose isolates, suggesting preference for lipid-rich environments. Single-cell RNA sequencing characterized CrF as both pro-fibrotic and pro-adipogenic with a rich milieu of activated immune cells responding to microbial stimuli, which we confirm in gnotobiotic mice colonized with C. innocuum. Ex vivo validation of expression patterns suggests C. innocuum stimulates tissue remodeling via M2 macrophages, leading to an adipose tissue barrier that serves to prevent systemic dissemination of bacteria.

RevDate: 2020-10-07

Schwartz DJ, Langdon AE, G Dantas (2020)

Understanding the impact of antibiotic perturbation on the human microbiome.

Genome medicine, 12(1):82.

The human gut microbiome is a dynamic collection of bacteria, archaea, fungi, and viruses that performs essential functions for immune development, pathogen colonization resistance, and food metabolism. Perturbation of the gut microbiome's ecological balance, commonly by antibiotics, can cause and exacerbate diseases. To predict and successfully rescue such perturbations, first, we must understand the underlying taxonomic and functional dynamics of the microbiome as it changes throughout infancy, childhood, and adulthood. We offer an overview of the healthy gut bacterial architecture over these life stages and comment on vulnerability to short and long courses of antibiotics. Second, the resilience of the microbiome after antibiotic perturbation depends on key characteristics, such as the nature, timing, duration, and spectrum of a course of antibiotics, as well as microbiome modulatory factors such as age, travel, underlying illness, antibiotic resistance pattern, and diet. In this review, we discuss acute and chronic antibiotic perturbations to the microbiome and resistome in the context of microbiome stability and dynamics. We specifically discuss key taxonomic and resistance gene changes that accompany antibiotic treatment of neonates, children, and adults. Restoration of a healthy gut microbial ecosystem after routine antibiotics will require rationally managed exposure to specific antibiotics and microbes. To that end, we review the use of fecal microbiota transplantation and probiotics to direct recolonization of the gut ecosystem. We conclude with our perspectives on how best to assess, predict, and aid recovery of the microbiome after antibiotic perturbation.

RevDate: 2020-10-01

Marazzato M, Zicari AM, Aleandri M, et al (2020)

16S Metagenomics Reveals Dysbiosis of Nasal Core Microbiota in Children With Chronic Nasal Inflammation: Role of Adenoid Hypertrophy and Allergic Rhinitis.

Frontiers in cellular and infection microbiology, 10:458.

Allergic rhinitis (AR) and adenoid hypertrophy (AH) are, in children, the main cause of partial or complete upper airway obstruction and reduction in airflow. However, limited data exist about the impact of the increased resistance to airflow, on the nasal microbial composition of children with AR end AH. Allergic rhinitis (AR) as well as adenoid hypertrophy (AH), represent extremely common pathologies in this population. Their known inflammatory obstruction is amplified when both pathologies coexist. In our study, the microbiota of anterior nares of 75 pediatric subjects with AR, AH or both conditions, was explored by 16S rRNA-based metagenomic approach. Our data show for the first time, that in children, the inflammatory state is associated to similar changes in the microbiota composition of AR and AH subjects respect to the healthy condition. Together with such alterations, we observed a reduced variability in the between-subject biodiversity on the other hand, these same alterations resulted amplified by the nasal obstruction that could constitute a secondary risk factor for dysbiosis. Significant differences in the relative abundance of specific microbial groups were found between diseased phenotypes and the controls. Most of these taxa belonged to a stable and quantitatively dominating component of the nasal microbiota and showed marked potentials in discriminating the controls from diseased subjects. A pauperization of the nasal microbial network was observed in diseased status in respect to the number of involved taxa and connectivity. Finally, while stable co-occurrence relationships were observed within both control- and diseases-associated microbial groups, only negative correlations were present between them, suggesting that microbial subgroups potentially act as maintainer of the eubiosis state in the nasal ecosystem. In the nasal ecosystem, inflammation-associated shifts seem to impact the more intimate component of the microbiota rather than representing the mere loss of microbial diversity. The discriminatory potential showed by differentially abundant taxa provide a starting point for future research with the potential to improve patient outcomes. Overall, our results underline the association of AH and AR with the impairment of the microbial interplay leading to unbalanced ecosystems.

RevDate: 2020-10-06

Son JW, Shoaie S, S Lee (2020)

Systems Biology: A Multi-Omics Integration Approach to Metabolism and the Microbiome.

Endocrinology and metabolism (Seoul, Korea), 35(3):507-514.

The complex and dynamic nature of human physiology, as exemplified by metabolism, has often been overlooked due to the lack of quantitative and systems approaches. Recently, systems biology approaches have pushed the boundaries of our current understanding of complex biochemical, physiological, and environmental interactions, enabling proactive medicine in the near future. From this perspective, we review how state-of-the-art computational modelling of human metabolism, i.e., genome-scale metabolic modelling, could be used to identify the metabolic footprints of diseases, to guide the design of personalized treatments, and to estimate the microbiome contributions to host metabolism. These state-of-the-art models can serve as a scaffold for integrating multi-omics data, thereby enabling the identification of signatures of dysregulated metabolism by systems approaches. For example, increased plasma mannose levels due to decreased uptake in the liver have been identified as a potential biomarker of early insulin resistance by multi-omics approaches. In addition, we also review the emerging axis of human physiology and the human microbiome, discussing its contribution to host metabolism and quantitative approaches to study its variations in individuals.

RevDate: 2020-09-27

Wright ML (2020)

Exploring the vaginal bacteriophage frontier.

BJOG : an international journal of obstetrics and gynaecology [Epub ahead of print].

Research evaluating the vaginal microbiome during pregnancy has largely focused on bacteria, although the most abundant component of the human microbiome are bacteriophages (phages). Phages, viruses that infect bacteria, have largely been neglected in vaginal microbiome research, largely due to limitations in isolating and characterizing phages from clinical samples.

RevDate: 2020-09-28

Daisley BA, Pitek AP, Chmiel JA, et al (2020)

Lactobacillus spp. attenuate antibiotic-induced immune and microbiota dysregulation in honey bees.

Communications biology, 3(1):534 pii:10.1038/s42003-020-01259-8.

Widespread antibiotic usage in apiculture contributes substantially to the global dissemination of antimicrobial resistance and has the potential to negatively influence bacterial symbionts of honey bees (Apis mellifera). Here, we show that routine antibiotic administration with oxytetracycline selectively increased tetB (efflux pump resistance gene) abundance in the gut microbiota of adult workers while concurrently depleting several key symbionts known to regulate immune function and nutrient metabolism such as Frischella perrera and Lactobacillus Firm-5 strains. These microbial changes were functionally characterized by decreased capped brood counts (marker of hive nutritional status and productivity) and reduced antimicrobial capacity of adult hemolymph (indicator of immune competence). Importantly, combination therapy with three immunostimulatory Lactobacillus strains could mitigate antibiotic-associated microbiota dysbiosis and immune deficits in adult workers, as well as maximize the intended benefit of oxytetracycline by suppressing larval pathogen loads to near-undetectable levels. We conclude that microbial-based therapeutics may offer a simple but effective solution to reduce honey bee disease burden, environmental xenobiotic exposure, and spread of antimicrobial resistance.

RevDate: 2020-09-25

Gail MH, Wan Y, J Shi (2020)

Power of Microbiome Beta-Diversity Analyses Based on Standard Reference Samples.

American journal of epidemiology pii:5911564 [Epub ahead of print].

A simple method to analyze microbiome beta-diversity computes mean beta-diversity distances from a test sample to standard reference samples. We used reference stool and nasal samples from the Human Microbiome Project and regressed an outcome on mean distances (2df-test) or additionally on squares and cross-product of mean distances (5df-test). We compared the power of 2df- and 5df-tests to the microbiome regression-based kernel association test (MiRKAT). In simulations, MiRKAT had moderately greater power than the 2df-test for discriminating skin versus saliva and skin versus nasal samples, but differences were negligible for skin versus stool and stool versus nasal samples. The 2df-test had slightly greater power than MiRKAT for Dirichlet-Multinomial samples. In associating body mass index with beta-diversity in stool samples from the American Gut Project, the 5df-test yielded smaller p-values than MiRKAT for most taxonomic levels and beta-diversity measures. Unlike procedures like MiRKAT that are based on the beta-diversity matrix, mean distances to reference samples can be analyzed with standard statistical tools and shared or meta-analyzed without sharing primary DNA data. Our data indicate that standard reference tests have comparable power to MiRKAT (and to permutational multivariate analysis of variance), but more simulations and applications are needed to confirm this.

RevDate: 2020-09-28

Kim GH, Rosiana S, Kirienko NV, et al (2020)

A Simple Nematode Infection Model for Studying Candida albicans Pathogenesis.

Current protocols in microbiology, 59(1):e114.

Candida albicans is an opportunistic fungal pathogen and a model organism to study fungal pathogenesis. It exists as a harmless commensal organism and member of the healthy human microbiome, but can cause life-threatening mucosal and systemic infections. A model host to study C. albicans infection and pathogenesis is the nematode Caenorhabditis elegans. C. elegans is frequently used as a model host to study microbial-host interactions because it can be infected by many human pathogens and there are also close morphological resemblances between the intestinal cells of C. elegans and mammals, where C. albicans infections can occur. This article outlines a detailed methodology for exploiting C. elegans as a host to study C. albicans infection, including a C. elegans egg preparation protocol and an agar-based C. elegans killing protocol to monitor fungal virulence. These protocols can additionally be used to study C. albicans genetic mutants in order to further our understanding of the genes involved in pathogenesis and virulence in C. albicans and the mechanisms of host-microbe interactions. © 2020 Wiley Periodicals LLC. Basic Protocol 1: Preparation of Caenorhabditis elegans eggs Support Protocol 1: Freezing and recovering Caenorhabditis elegans Support Protocol 2: Making superfood agar and OP50 plates Basic Protocol 2: Caenorhabditis elegans/Candida albicans agar killing assay Support Protocol 3: Constructing a worm pick.

RevDate: 2020-09-28

Rasinkangas P, Tytgat HLP, Ritari J, et al (2020)

Characterization of Highly Mucus-Adherent Non-GMO Derivatives of Lacticaseibacillus rhamnosus GG.

Frontiers in bioengineering and biotechnology, 8:1024.

Lacticaseibacillus rhamnosus GG is one of the best studied lactic acid bacteria in the context of probiotic effects. L. rhamnosus GG has been shown to prevent diarrhea in children and adults and has been implicated to have mitigating or preventive effects in several disorders connected to microbiota dysbiosis. The probiotic effects are largely attributed to its adhesive heterotrimeric sortase-dependent pili, encoded by the spaCBA-srtC1 gene cluster. Indeed, the strain-specific SpaCBA pili have been shown to contribute to adherence, biofilm formation and host signaling. In this work we set out to generate non-GMO derivatives of L. rhamnosus GG that adhere stronger to mucus compared to the wild-type strain using chemical mutagenesis. We selected 13 derivatives that showed an increased mucus-adherent phenotype. Deep shotgun resequencing of the strains enabled division of the strains into three classes, two of which revealed SNPs (single nucleotide polymorphisms) in the spaA and spaC genes encoding the shaft and tip adhesive pilins, respectively. Strikingly, the other class derivatives demonstrated less clear genotype - phenotype relationships, illustrating that pili biogenesis and structure is also affected by other processes. Further characterization of the different classes of derivatives was performed by PacBio SMRT sequencing and RNAseq analysis, which resulted in the identification of molecular candidates driving pilin biosynthesis and functionality. In conclusion, we report on the generation and characterization of three classes of strongly adherent L. rhamnosus GG derivatives that show an increase in adhesion to mucus. These are of special interest as they provide a window on processes and genes driving piliation and its control in L. rhamnosus GG and offer a variety of non-GMO derivatives of this key probiotic strain that are applicable in food products.

RevDate: 2020-10-13
CmpDate: 2020-10-13

Daisley BA, Chanyi RM, Abdur-Rashid K, et al (2020)

Abiraterone acetate preferentially enriches for the gut commensal Akkermansia muciniphila in castrate-resistant prostate cancer patients.

Nature communications, 11(1):4822.

Abiraterone acetate (AA) is an inhibitor of androgen biosynthesis, though this cannot fully explain its efficacy against androgen-independent prostate cancer. Here, we demonstrate that androgen deprivation therapy depletes androgen-utilizing Corynebacterium spp. in prostate cancer patients and that oral AA further enriches for the health-associated commensal, Akkermansia muciniphila. Functional inferencing elucidates a coinciding increase in bacterial biosynthesis of vitamin K2 (an inhibitor of androgen dependent and independent tumor growth). These results are highly reproducible in a host-free gut model, excluding the possibility of immune involvement. Further investigation reveals that AA is metabolized by bacteria in vitro and that breakdown components selectively impact growth. We conclude that A. muciniphila is a key regulator of AA-mediated restructuring of microbial communities, and that this species may affect treatment response in castrate-resistant cohorts. Ongoing initiatives aimed at modulating the colonic microbiota of cancer patients may consider targeted delivery of poorly absorbed selective bacterial growth agents.

RevDate: 2020-09-25

Balty C, Guillot A, Fradale L, et al (2020)

Biosynthesis of the sactipeptide Ruminococcin C by the human microbiome: Mechanistic insights into thioether bond formation by radical SAM enzymes.

The Journal of biological chemistry pii:RA120.015371 [Epub ahead of print].

Despite its major importance in human health, the metabolic potential of the human gut microbiota is still poorly understood. We have recently shown that biosynthesis of Ruminococcin C (RumC), a novel ribosomally synthesized and post-translationally modified peptide (RiPP) produced by the commensal bacterium Ruminococcus gnavus, requires two radical SAM enzymes (RumMC1 and RumMC2) catalyzing the formation of four Cα-thioether bridges. These bridges, which are essential for RumC's antibiotic properties against human pathogens such as Clostridium perfringens, define two hairpin domains giving this sactipeptide (sulfur-to-α-carbon thioether-containing peptide) an unusual architecture among natural products. We report here the biochemical and spectroscopic characterizations of RumMC2. EPR spectroscopy and mutagenesis data support that RumMC2 is a member of the large family of SPASM-domain radical SAM enzymes characterized by the presence of three [4Fe-4S] clusters. We also demonstrate that this enzyme initiates its reaction by Cα H-atom abstraction and is able to catalyze the formation of non-natural thioether bonds in engineered peptide substrates. Unexpectedly, our data support the formation of a ketoimine rather than an α,β-dehydro-amino acid intermediate during Cα-thioether bridge LC-MS/MS fragmentation. Finally, we explored the roles of the leader peptide and of the RiPP precursor peptide recognition element (RRE), present in myriad RiPP-modifying enzymes. Collectively, our data support a more complex role for the RRE and the core peptide for the installation of post-translational modifications in RiPPs than previously anticipated and suggest a possible reaction intermediate for thioether bond formation.

RevDate: 2020-10-13

AlShahrani I, Hosmani J, AlShahrani A, et al (2020)

High altitude as a possible factor for dysbiosis of salivary microbiome in orthodontic patients.

Archives of oral biology, 119:104917 pii:S0003-9969(20)30295-8 [Epub ahead of print].

BACKGROUND: External stressors such as high altitude and low oxygen are known to affect the human microbiome, and in light of the increased occurrence of dental caries and periodontitis in orthodontic patients, the effect of high altitude and the altered oral environment in orthodontic patients on the oral salivary microbiome was researched.

MATERIALS & METHODS: 31 orthodontic patients from high altitude, Aseer region and 25 orthodontic patients, residing at sea level, as controls were included. DNA isolation was done from the saliva collected from the study participants. V3 area of 16s RNA was targeted by universal primers through PCR to decipher the salivary microbiome in both the groups.

RESULTS: A total of 11 genera belonging to 4 phyla of bacteria were identified in both groups. The most abundant microbiome at the phylum level was: Firmicutes, Bacteroidetes Proteobacteria, and Cyanobacteria. The salivary microbiome was more diverse in sea level controls compared to that of the orthodontic patients at high altitude wherein the presence of only two main phyla: Firmicutes and Proteobacteria were seen. The controls revealed Firmicutes, Proteobacteria, Bacteroidetes and Cyanobacteria.

CONCLUSIONS: The findings of the study suggest that the biodiversity of the salivary microbiome is severely perturbed under the cumulative influences of high altitude and presence of fixed orthodontic appliance. Under these circumstances, a strict and meticulous oral hygiene regimen should be recommended and followed to avoid harmful effects on the periodontal tissues.

RevDate: 2020-09-28

Kim B, Cho EJ, Yoon JH, et al (2020)

Pathway-Based Integrative Analysis of Metabolome and Microbiome Data from Hepatocellular Carcinoma and Liver Cirrhosis Patients.

Cancers, 12(9): pii:cancers12092705.

Aberrations of the human microbiome are associated with diverse liver diseases, including hepatocellular carcinoma (HCC). Even if we can associate specific microbes with particular diseases, it is difficult to know mechanistically how the microbe contributes to the pathophysiology. Here, we sought to reveal the functional potential of the HCC-associated microbiome with the human metabolome which is known to play a role in connecting host phenotype to microbiome function. To utilize both microbiome and metabolomic data sets, we propose an innovative, pathway-based analysis, Hierarchical structural Component Model for pathway analysis of Microbiome and Metabolome (HisCoM-MnM), for integrating microbiome and metabolomic data. In particular, we used pathway information to integrate these two omics data sets, thus providing insight into biological interactions between different biological layers, with regard to the host's phenotype. The application of HisCoM-MnM to data sets from 103 and 97 patients with HCC and liver cirrhosis (LC), respectively, showed that this approach could identify HCC-related pathways related to cancer metabolic reprogramming, in addition to the significant metabolome and metagenome that make up those pathways.

RevDate: 2020-09-23

Morar N, JA Skorburg (2020)

Why We Never Eat Alone: The Overlooked Role of Microbes and Partners in Obesity Debates in Bioethics.

Journal of bioethical inquiry pii:10.1007/s11673-020-10047-2 [Epub ahead of print].

Debates about obesity in bioethics tend to unfold in predictable epicycles between individual choices and behaviours (e.g., restraint, diet, exercise) and the oppressive socio-economic structures constraining them (e.g., food deserts, advertising). Here, we argue that recent work from two cutting-edge research programmes in microbiology and social psychology can advance this conceptual stalemate in the literature. We begin in section 1 by discussing two promising lines of obesity research involving the human microbiome and relationship partners. Then, in section 2, we show how this research has made viable novel strategies for fighting obesity, including microbial therapies and dyad-level interventions. Finally, in section 3, we consider objections to our account and conclude by arguing that attention to the most immediate features of our biological and social environment offers a middle ground solution, while also raising important new issues for bioethicists.

RevDate: 2020-09-22

Sainz T, Delgado J, Méndez-Echevarría A, et al (2020)

The clinical relevance of the microbiome when managing paediatric infectious diseases.

Acta paediatrica (Oslo, Norway : 1992) [Epub ahead of print].

In recent years, the field of infectious diseases has been hit by the overwhelming amount of information generated while the human microbiome is being disentangled. Based on the interaction between the microbiota and the immune system, the implications regarding infectious diseases are probably major and remain a challenge. This review was conceived as a comprehensive tool to provide an overview of the available evidence regarding the influence of the microbiome on infectious diseases in children. We present the main findings aroused from microbiome research in prevention, diagnosis and treatment of infectious disease under a pediatric perspective, to inform clinicians of the potential relevance of microbiome-related knowledge for translation to clinical practice. CONCLUSION: The evidence shown in this review highlights the numerous research gaps ahead and supports the need to move forward to integrating the so-called microbiome thinking into our routine clinical practice.


ESP Quick Facts

ESP Origins

In the early 1990's, Robert Robbins was a faculty member at Johns Hopkins, where he directed the informatics core of GDB — the human gene-mapping database of the international human genome project. To share papers with colleagues around the world, he set up a small paper-sharing section on his personal web page. This small project evolved into The Electronic Scholarly Publishing Project.

ESP Support

In 1995, Robbins became the VP/IT of the Fred Hutchinson Cancer Research Center in Seattle, WA. Soon after arriving in Seattle, Robbins secured funding, through the ELSI component of the US Human Genome Project, to create the original ESP.ORG web site, with the formal goal of providing free, world-wide access to the literature of classical genetics.

ESP Rationale

Although the methods of molecular biology can seem almost magical to the uninitiated, the original techniques of classical genetics are readily appreciated by one and all: cross individuals that differ in some inherited trait, collect all of the progeny, score their attributes, and propose mechanisms to explain the patterns of inheritance observed.

ESP Goal

In reading the early works of classical genetics, one is drawn, almost inexorably, into ever more complex models, until molecular explanations begin to seem both necessary and natural. At that point, the tools for understanding genome research are at hand. Assisting readers reach this point was the original goal of The Electronic Scholarly Publishing Project.

ESP Usage

Usage of the site grew rapidly and has remained high. Faculty began to use the site for their assigned readings. Other on-line publishers, ranging from The New York Times to Nature referenced ESP materials in their own publications. Nobel laureates (e.g., Joshua Lederberg) regularly used the site and even wrote to suggest changes and improvements.

ESP Content

When the site began, no journals were making their early content available in digital format. As a result, ESP was obliged to digitize classic literature before it could be made available. For many important papers — such as Mendel's original paper or the first genetic map — ESP had to produce entirely new typeset versions of the works, if they were to be available in a high-quality format.

ESP Help

Early support from the DOE component of the Human Genome Project was critically important for getting the ESP project on a firm foundation. Since that funding ended (nearly 20 years ago), the project has been operated as a purely volunteer effort. Anyone wishing to assist in these efforts should send an email to Robbins.

ESP Plans

With the development of methods for adding typeset side notes to PDF files, the ESP project now plans to add annotated versions of some classical papers to its holdings. We also plan to add new reference and pedagogical material. We have already started providing regularly updated, comprehensive bibliographies to the ESP.ORG site.

Electronic Scholarly Publishing
961 Red Tail Lane
Bellingham, WA 98226

E-mail: RJR8222 @

Papers in Classical Genetics

The ESP began as an effort to share a handful of key papers from the early days of classical genetics. Now the collection has grown to include hundreds of papers, in full-text format.

Digital Books

Along with papers on classical genetics, ESP offers a collection of full-text digital books, including many works by Darwin (and even a collection of poetry — Chicago Poems by Carl Sandburg).


ESP now offers a much improved and expanded collection of timelines, designed to give the user choice over subject matter and dates.


Biographical information about many key scientists.

Selected Bibliographies

Bibliographies on several topics of potential interest to the ESP community are now being automatically maintained and generated on the ESP site.

ESP Picks from Around the Web (updated 07 JUL 2018 )