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Bibliography on: Human Microbiome

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ESP: PubMed Auto Bibliography 20 Mar 2019 at 01:43 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: 2019-03-19

LaPierre N, Ju CJ, Zhou G, et al (2019)

MetaPheno: A Critical Evaluation of Deep Learning and Machine Learning in Metagenome-Based Disease Prediction.

Methods (San Diego, Calif.) pii:S1046-2023(18)30362-1 [Epub ahead of print].

The human microbiome plays a number of critical roles, impacting almost every aspect of human health and well-being. Conditions in the microbiome have been linked to a num-ber of significant diseases. Additionally, revolutions in sequencing technology have led to a rapid increase in publicly-available sequencing data. Consequently, there have been grow-ing efforts to predict disease status from metagenomic sequencing data, with a proliferation of new approaches in the last few years. Some of these efforts have explored utilizing a powerful form of machine learning called deep learning, which has been applied successfully in several biological domains. Here, we review some of these methods and the algorithms that they are based on, with a particular focus on deep learning methods. We also per-form a deeper analysis of Type 2 Diabetes and obesity datasets that have eluded improved results, using a variety of machine learning and feature extraction methods. We conclude by offering perspectives on study design considerations that may impact results and future directions the field can take to improve results and offer more valuable conclusions. The scripts and extracted features for the analyses conducted in this paper are available via GitHub:

RevDate: 2019-03-18

Cohen LJ, Cho JH, Gevers D, et al (2019)

Genetic Factors and the Intestinal Microbiome Guide Development of Microbe-based Therapies for Inflammatory Bowel Diseases.

Gastroenterology pii:S0016-5085(19)33559-0 [Epub ahead of print].

The intestinal microbiota is a dynamic community of bacteria, fungi, and viruses that mediates mucosal homeostasis and physiology. Imbalances in the microbiome and aberrant immune responses to gut bacteria can disrupt homeostasis and are associated with inflammatory bowel diseases (IBD) in humans and colitis in mice. We review genetic variants associated with IBD and their effects on the intestinal microbiome, the immune response, and disease pathogenesis. The intestinal microbiome, which includes microbial antigens, adjuvants, and metabolic products, affects the development and function of the intestinal mucosa and inflammatory responses in the gut. Strategies to manipulate the microbiome might therefore be used in treatment of IBD. We review microbe-based therapies for IBD and the potential to engineer patients' intestinal microbiota. We discuss how studies of patients with IBD and mouse models have advanced our understanding of the interactions between genetic factors and the gut microbiome, and challenges to development of microbe-based therapies for IBD.

RevDate: 2019-03-16

Shaw LP, Bassam H, Barnes CP, et al (2019)

Modelling microbiome recovery after antibiotics using a stability landscape framework.

The ISME journal pii:10.1038/s41396-019-0392-1 [Epub ahead of print].

Treatment with antibiotics is one of the most extreme perturbations to the human microbiome. Even standard courses of antibiotics dramatically reduce the microbiome's diversity and can cause transitions to dysbiotic states. Conceptually, this is often described as a 'stability landscape': the microbiome sits in a landscape with multiple stable equilibria, and sufficiently strong perturbations can shift the microbiome from its normal equilibrium to another state. However, this picture is only qualitative and has not been incorporated in previous mathematical models of the effects of antibiotics. Here, we outline a simple quantitative model based on the stability landscape concept and demonstrate its success on real data. Our analytical impulse-response model has minimal assumptions with three parameters. We fit this model in a Bayesian framework to data from a previous study of the year-long effects of short courses of four common antibiotics on the gut and oral microbiomes, allowing us to compare parameters between antibiotics and microbiomes, and further validate our model using data from another study looking at the impact of a combination of last-resort antibiotics on the gut microbiome. Using Bayesian model selection we find support for a long-term transition to an alternative microbiome state after courses of certain antibiotics in both the gut and oral microbiomes. Quantitative stability landscape frameworks are an exciting avenue for future microbiome modelling.

RevDate: 2019-03-16

Douillard FP, WM de Vos (2019)

Biotechnology of health-promoting bacteria.

Biotechnology advances pii:S0734-9750(19)30044-8 [Epub ahead of print].

Over the last decade, there has been an increasing scientific and public interest in bacteria that may positively contribute to human gut health and well-being. This interest is reflected by the ever-increasing number of developed functional food products containing health-promoting bacteria and reaching the market place as well as by the growing revenue and profits of notably bacterial supplements worldwide. Traditionally, the origin of probiotic-marketed bacteria was limited to a rather small number of bacterial species that mostly belong to lactic acid bacteria and bifidobacteria. Intensifying research efforts on the human gut microbiome offered novel insights into the role of human gut microbiota in health and disease, while also providing a deep and increasingly comprehensive understanding of the bacterial communities present in this complex ecosystem and their interactions with the gut-liver-brain axis. This resulted in rational and systematic approaches to select novel health-promoting bacteria or to engineer existing bacteria with enhanced probiotic properties. In parallel, the field of gut microbiomics developed into a fertile framework for the identification, isolation and characterization of a phylogenetically diverse array of health-promoting bacterial species, also called next-generation therapeutic bacteria. The present review will address these developments with specific attention for the selection and improvement of a selected number of health-promoting bacterial species and strains that are extensively studied or hold promise for future food or pharma product development.

RevDate: 2019-03-15

Minot SS (2019)

De novo Assembly Vastly Expands the Known Microbial Universe.

Trends in microbiology pii:S0966-842X(19)30058-7 [Epub ahead of print].

The study of the human microbiome relies heavily on the genomes of bacterial isolates that can be grown in culture. A recent study (Pasolli et al. Cell 2019;176:649-662) of stool microbiome samples generated over 150 000 microbial genomes without any culture, vastly expanding our knowledge of the biases in existing reference databases.

RevDate: 2019-03-15

Perz AI, Giles CB, Brown CA, et al (2019)

MNEMONIC: MetageNomic Experiment Mining to create an OTU Network of Inhabitant Correlations.

BMC bioinformatics, 20(Suppl 2):96 pii:10.1186/s12859-019-2623-x.

BACKGROUND: The number of publicly available metagenomic experiments in various environments has been rapidly growing, empowering the potential to identify similar shifts in species abundance between different experiments. This could be a potentially powerful way to interpret new experiments, by identifying common themes and causes behind changes in species abundance.

RESULTS: We propose a novel framework for comparing microbial shifts between conditions. Using data from one of the largest human metagenome projects to date, the American Gut Project (AGP), we obtain differential abundance vectors for microbes using experimental condition information provided with the AGP metadata, such as patient age, dietary habits, or health status. We show it can be used to identify similar and opposing shifts in microbial species, and infer putative interactions between microbes. Our results show that groups of shifts with similar effects on microbiome can be identified and that similar dietary interventions display similar microbial abundance shifts.

CONCLUSIONS: Without comparison to prior data, it is difficult for experimentalists to know if their observed changes in species abundance have been observed by others, both in their conditions and in others they would never consider comparable. Yet, this can be a very important contextual factor in interpreting the significance of a shift. We've proposed and tested an algorithmic solution to this problem, which also allows for comparing the metagenomic signature shifts between conditions in the existing body of data.

RevDate: 2019-03-14

Burcham ZM, Schmidt CJ, Pechal JL, et al (2019)

Detection of critical antibiotic resistance genes through routine microbiome surveillance.

PloS one, 14(3):e0213280 pii:PONE-D-18-26200.

Population-based public health data on antibiotic resistance gene carriage is poorly surveyed. Research of the human microbiome as an antibiotic resistance reservoir has primarily focused on gut associated microbial communities, but data have shown more widespread microbial colonization across organs than originally believed, with organs previously considered as sterile being colonized. Our study demonstrates the utility of postmortem microbiome sampling during routine autopsy as a method to survey antibiotic resistance carriage in a general population. Postmortem microbial sampling detected pathogens of public health concern including genes for multidrug efflux pumps, carbapenem, methicillin, vancomycin, and polymixin resistances. Results suggest that postmortem assessments of host-associated microbial communities are useful in acquiring community specific data while reducing selective-participant biases.

RevDate: 2019-03-14

Elzinga J, van der Oost J, de Vos WM, et al (2019)

The Use of Defined Microbial Communities To Model Host-Microbe Interactions in the Human Gut.

Microbiology and molecular biology reviews : MMBR, 83(2): pii:83/2/e00054-18.

SUMMARYThe human intestinal ecosystem is characterized by a complex interplay between different microorganisms and the host. The high variation within the human population further complicates the quest toward an adequate understanding of this complex system that is so relevant to human health and well-being. To study host-microbe interactions, defined synthetic bacterial communities have been introduced in gnotobiotic animals or in sophisticated in vitro cell models. This review reinforces that our limited understanding has often hampered the appropriate design of defined communities that represent the human gut microbiota. On top of this, some communities have been applied to in vivo models that differ appreciably from the human host. In this review, the advantages and disadvantages of using defined microbial communities are outlined, and suggestions for future improvement of host-microbe interaction models are provided. With respect to the host, technological advances, such as the development of a gut-on-a-chip system and intestinal organoids, may contribute to more-accurate in vitro models of the human host. With respect to the microbiota, due to the increasing availability of representative cultured isolates and their genomic sequences, our understanding and controllability of the human gut "core microbiota" are likely to increase. Taken together, these advancements could further unravel the molecular mechanisms underlying the human gut microbiota superorganism. Such a gain of insight would provide a solid basis for the improvement of pre-, pro-, and synbiotics as well as the development of new therapeutic microbes.

RevDate: 2019-03-13

Plantinga AM, Chen J, Jenq RR, et al (2019)

pldist: ecological dissimilarities for paired and longitudinal microbiome association analysis.

Bioinformatics (Oxford, England) pii:5341424 [Epub ahead of print].

MOTIVATION: The human microbiome is notoriously variable across individuals, with a wide range of 'healthy' microbiomes. Paired and longitudinal studies of the microbiome have become increasingly popular as a way to reduce unmeasured confounding and to increase statistical power by reducing large inter-subject variability. Statistical methods for analyzing such datasets are scarce.

RESULTS: We introduce a paired UniFrac dissimilarity that summarizes within-individual (or within-pair) shifts in microbiome composition and then compares these compositional shifts across individuals (or pairs). This dissimilarity depends on a novel transformation of relative abundances, which we then extend to more than two time points and incorporate into several phylogenetic and non-phylogenetic dissimilarities. The data transformation and resulting dissimilarities may be used in a wide variety of downstream analyses, including ordination analysis and distance-based hypothesis testing. Simulations demonstrate that tests based on these dissimilarities retain appropriate type 1 error and high power. We apply the method in two real datasets.

The R package pldist is available on GitHub at

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

RevDate: 2019-03-08

Buchta V (2018)

Vaginal microbiome.

Ceska gynekologie, 83(5):371-379.

OBJECTIVE: Presentation of complex information about the vaginal microbiota from historical view to current concepts with focus on latest findings on the structure and functioning of the vaginal microbiome.

DESIGN: Review article.

SETTING: Department of Clinical Microbiology, University Hospital and Faculty of Medicine in Hradci Králové, Charles University in Prague.

METHODS: Literature review using the databases (PubMed, Web of Science, Ovid, etc.) with keywords (vaginal microbiota/ microbiom; vaginal discharge; bacterial vaginosis; vulvovaginitis; vaginal Lactobacillus).

RESULTS: The vaginal microbiome is a specific compartment of the human microbiome. Unique conditions of the vagina are characterized by a few microbial species, usually lactobacilli, which are able to utilize glycogen, which is under control of estrogens. Lactobacilli and other fermentative bacteria together with vaginal epithelial cells produce lactic acid and are responsible for acidifying vaginal milieu. Lactic acid occurs in two isomeric forms, and their relative ratio is likely to give the vaginal microbiota a certain degree of stability and ability to withstand some infections. This microbiota is manifested by a low degree of diversity and by the high dynamics of changes of its composition under the influence of various exogenous and endogenous factors. Increase in diversity can be paradoxically associated with a dysbiosis such as bacterial vaginosis. Individual species of lactobacilli mainly Lactobacillus crispatus characterize the main community state types in the vagina. Apart from lactobacilli, healthy women may be colonized with a non-lactobacillary microbiota whose rate is dependent on ethnicity.

CONCLUSION: The definition of vaginal microbiota cannot be only related to the presence or absence of individual microorganisms, although the incidence of some of them can be correlated with dysbiosis or eubiosis. The composition of microbiota is important, but it is only one of the basic attributes of normal vaginal microbiota, but not sufficient; that is the functional definition of vaginal microbiota in relation to its structure and dynamics, including the influence of ethnicity, physiological status of the vagina, and genetic disposition of woman.

RevDate: 2019-03-07

Salvucci E (2019)

The human-microbiome superorganism and its modulation to restore health.

International journal of food sciences and nutrition [Epub ahead of print].

Microbiome is the community of microorganism that co-live with a host. The human being is the result of the integration of its genome and the coexistence with millions of microorganisms throughout its evolutionary history. Human-microbiome association can be considered a step of integration in evolution, constituting a superorganism. Many emergent diseases are related to the loss of part of this microbiome and its restoration can be achieved by different strategies. Gut microbiome imbalance is particularly associated with numerous inflammatory, immune and nervous system-related diseases by a communication pathway called microbiome-brain axis. Modulation of microbiome by administering prebiotics, like arabinoxylans, and synbiotics is a plausible treatment for dysbiosis, the regulation of neurotransmitters and alleviation of neurological manifestations.

RevDate: 2019-03-05

Rego S, Dagan-Rosenfeld O, Bivona SA, et al (2019)

Much ado about nothing: A qualitative study of the experiences of an average-risk population receiving results of exome sequencing.

Journal of genetic counseling [Epub ahead of print].

The increasing availability of exome sequencing to the general ("healthy") population raises questions about the implications of genomic testing for individuals without suspected Mendelian diseases. Little is known about this population's motivations for undergoing exome sequencing, their expectations, reactions, and perceptions of utility. In order to address these questions, we conducted in-depth semi-structured interviews with 12 participants recruited from a longitudinal multi-omics profiling study that included exome sequencing. Participants were interviewed after receiving exome results, which included Mendelian disease-associated pathogenic and likely pathogenic variants, pharmacogenetic variants, and risk assessments for multifactorial diseases such as type 2 diabetes. The primary motivation driving participation in exome sequencing was personal curiosity. While they reported feeling validation and relief, participants were frequently underwhelmed by the results and described having expected more from exome sequencing. All participants reported discussing the results with at least some family, friends, and healthcare providers. Participants' recollection of the results returned to them was sometimes incorrect or incomplete, in many cases aligning with their perceptions of their health risks when entering the study. These results underscore the need for different genetic counseling approaches for generally healthy patients undergoing exome sequencing, in particular the need to provide anticipatory guidance to moderate participants' expectations. They also provide a preview of potential challenges clinicians may face as genomic sequencing continues to scale-up in the general population despite a lack of full understanding of its impact.

RevDate: 2019-03-05

Haahtela T (2019)

A Biodiversity Hypothesis.

Allergy [Epub ahead of print].

Biodiversity hypothesis states, that contact with natural environments enriches the human microbiome, promotes immune balance and protects from allergy and inflammatory disorders. We are protected by two nested layers of biodiversity, microbiota of the outer layer (soil, natural waters, plants, animals) and inner layer (gut, skin, airways). The latter inhabits our body and is colonized from the outer layer. Explosion of human populations along with cultural evolution are profoundly changing our environment and lifestyle. Adaptive immunoregulatory circuits and dynamic homestasis are at stake in the newly emerged urban surroundings. In allergy, and chronic inflammatory disorders in general, exploring the determinants of immunotolerance is the key for prevention and more effective treatment. Loss of immunoprotective factors, derived from nature, is a new kind of health risk poorly acknowledged until recently. The paradigm change has been implemented in the Finnish allergy programme (2008-2018), which emphasized tolerance instead of avoidance. The first results are promising, as allergy burden has started to reduce. The rapidly urbanizing world is facing serious biodiversity loss with global warming, which are interconnected. Biodiversity hypothesis of health and disease has societal impact, e.g. on city planning, food and energy production and nature conservation. It has also a message for individuals for health and wellbeing: take nature close, to touch, eat, breathe, experience and enjoy. Biodiverse natural environments are dependent on planetary health, which should be a priority also among health professionals. This article is protected by copyright. All rights reserved.

RevDate: 2019-03-05

Wallace DJ, Sayre NL, Patterson TT, et al (2019)

Spinal cord injury and the human microbiome: beyond the brain-gut axis.

Neurosurgical focus, 46(3):E11.

In addition to standard management for the treatment of the acute phase of spinal cord injury (SCI), implementation of novel neuroprotective interventions offers the potential for significant reductions in morbidity and long-term health costs. A better understanding of the systemic changes after SCI could provide insight into mechanisms that lead to secondary injury. An emerging area of research involves the complex interplay of the gut microbiome and the CNS, i.e., a brain-gut axis, or perhaps more appropriately, a CNS-gut axis. This review summarizes the relevant literature relating to the gut microbiome and SCI. Experimental models in stroke and traumatic brain injury demonstrate the bidirectional communication of the CNS to the gut with postinjury dysbiosis, gastrointestinal-associated lymphoid tissue-mediated neuroinflammatory responses, and bacterial-metabolite neurotransmission. Similar findings are being elucidated in SCI as well. Experimental interventions in these areas have shown promise in improving functional outcomes in animal models. This commensal relationship between the human body and its microbiome, particularly the gut microbiome, represents an exciting frontier in experimental medicine.

RevDate: 2019-03-05

Meyer F, Bremges A, Belmann P, et al (2019)

Assessing taxonomic metagenome profilers with OPAL.

Genome biology, 20(1):51 pii:10.1186/s13059-019-1646-y.

The explosive growth in taxonomic metagenome profiling methods over the past years has created a need for systematic comparisons using relevant performance criteria. The Open-community Profiling Assessment tooL (OPAL) implements commonly used performance metrics, including those of the first challenge of the initiative for the Critical Assessment of Metagenome Interpretation (CAMI), together with convenient visualizations. In addition, we perform in-depth performance comparisons with seven profilers on datasets of CAMI and the Human Microbiome Project. OPAL is freely available at .

RevDate: 2019-03-04

Piersigilli F, Lam TT, Vernocchi P, et al (2019)

Identification of new biomarkers of bronchopulmonary dysplasia using metabolomics.

Metabolomics : Official journal of the Metabolomic Society, 15(2):20 pii:10.1007/s11306-019-1482-9.

OBJECTIVE: To identify new biomarkers of bronchopulmonary dysplasia (BPD) in preterm neonates.

STUDY DESIGN: Metabolomic study of prospectively collected tracheal aspirate (TA) samples from preterm neonates admitted in 2 neonatal intensive care units measured by a mass spectroscopy-based assay and analysed using partial least squares-discriminant analysis.

RESULTS: We evaluated 160 TA samples from 68 neonates, 44 with BPD and 24 without BPD in the first week of life. A cluster of 53 metabolites was identified as characteristic of BPD, with 18 select metabolites being highly significant in the separation of BPD versus No BPD. To control for the gestational age (GA) differences, we did a sub-group analyses, and noted that the amino acids histidine, glutamic acid, citrulline, glycine and isoleucine levels were higher in neonates with BPD. In addition, acylcarnitines C16-OH and C18:1-OH were also higher in neonates who developed BPD, but especially in the most preterm infants (neonates with GA < 27 weeks).

CONCLUSION: Metabolomics is a promising approach to identify novel specific biomarkers for BPD.

RevDate: 2019-03-04

Reid G (2019)

Disentangling What We Know About Microbes and Mental Health.

Frontiers in endocrinology, 10:81.

Much has been written in recent years about the gut-brain axis. Exciting pilot studies suggest probiotic applications to the gut can reduce anxiety and depression via the vagus nerve. But not to diminish such findings, much still needs to be considered, including the fact that the vagus nerve links to many other body sites that also host a microbiome. Questions remain that touch the core of being human: (i) Do our microbes influence happiness and to what extent? (ii) What components of the gut microbiota and their function, including as it relates to mental health, are critical and how do they differ between agile, fit hunter gatherers and obese westerners or Danes described as the happiest people on the planet? (iii) What role do environmental pollutants play in this microbes-host ecosystem? While approaching life from a reductionist perspective has a long history in science, we need to try to interrogate these health and disease issues from a wider perspective. For verification of a link between the gut microbiota and brain, and to test new therapies, human studies are needed, and are long overdue.

RevDate: 2019-02-28

Wang Z, Saha S, Van Horn S, et al (2018)

Gut microbiome differences between metformin- and liraglutide-treated T2DM subjects.

Endocrinology, diabetes & metabolism, 1(1):e00009 pii:EDM29.

Introduction: Metformin and glucagon-like peptide-1 (GLP-1) agonists are widely used for treating type two diabetes mellitus (T2DM). While recent studies suggest these drugs might modify the gastrointestinal tract (GIT) microbiome, further confirmation is required from human clinical trials.

Materials and methods: Here, we compare, in patients with T2DM, the effects of metformin (n = 18 subjects) and liraglutide (n = 19), a GLP-1 agonist, on their GIT microbiomes over a 42 day period (n = 74 samples) using 16S ribosomal RNA (rRNA) sequencing.

Results: We found that these drugs had markedly different effects on the microbiome composition. At both baseline and Day 42, subjects taking metformin had a significant increase (Baseline adj. P = .038, Day 42 adj. P = .041) in the relative abundance of the bacterial genus Sutterella, whereas liraglutide dosing is associated with a significant increase (Baseline adj. P = .048, Day 42 adj. P = .003) in the genus Akkermansia, a GIT bacteria positively associated with gut barrier homoeostasis. Bacteroides and Akkermansia relative abundances were also significantly associated with duration of subject diabetes (adj P < .05). Specifically, there was a significantly higher abundance of Akkermansia in subjects with short and medium durations than those with long duration of diabetes.

Discussion: To our knowledge, this is the first report of GLP-1 agonist-associated changes in the human microbiome and its differentiating effects to metformin. Our study suggests that modulation of the GIT microbiome is a potentially important component in the mechanism of action of these drugs.

RevDate: 2019-02-28

Song Z, Wang X, Zhou X, et al (2019)

Taxonomic Distribution of FosB in Human-Microbiota and Activity Comparison of Fosfomycin Resistance.

Frontiers in microbiology, 10:200.

FosB, a Mg2+ dependent thioltransferase, confers antibiotic resistance to fosfomycin through enzymatic drug inactivation. Among all antibiotic resistant proteins in the Antibiotic Resistance Genes Database and the Comprehensive Antibiotic Resistance Database, FosB is within 5% of the most number of ARPs identified in Human Microbiome Project reference database but mainly distributed in limited genera, i.e., 122 of total 133 FosB homologues are found from Bacillus and Staphylococcus. Furthermore, these FosB sequences could be divided into three clusters based on their phylogenetic relationship, i.e., two groups of FosB were mainly from Bacillus, and another was mainly from Staphylococcus. Finally, we confirmed that FosB from the group of Staphylococcus presented the highest resistance ability to fosfomycin by in silico and in vitro comparisons. In summary, this study elaborates the specific taxonomic characteristics and resistant abilities of FosB in human microbiota, which might help in developing more promising fosfomycin-like antibiotics.

RevDate: 2019-02-27

Shan Y, Wu W, Fan W, et al (2019)

House dust microbiome and human health risks.

International microbiology : the official journal of the Spanish Society for Microbiology pii:10.1007/s10123-019-00057-5 [Epub ahead of print].

People spend a lot of time indoors and the indoor microbiome is a major part of the environment that we are exposed to. However, awareness of the exposure to the indoor microbiome and its health effects remains poor. Outdoor environment (soil and air), indoor sources (ventilation, dampness and building materials), human occupants, and pets compose the indoor microbial community. It has been estimated that up to 500-1000 different species can be present in house dust. House dust is a major source and reservoir of indoor microbiome, which influences human microbiome and determines health and disease. Herein, we review the origins and the components of the fungal and bacterial communities in house dust and their possible effect on human health, in particular on allergic disorders, intestinal microbiome, and immune responses. We expect to lay a solid foundation for the further study on the mechanisms of how the house dust microbes interact with the host microbiome and the human immune system.

RevDate: 2019-02-27

Falony G, Vandeputte D, Caenepeel C, et al (2019)

The human microbiome in health and disease: hype or hope.

Acta clinica Belgica [Epub ahead of print].

OBJECTIVES: The prognostic, diagnostic, and therapeutic potential of the human gut microbiota is widely recognised. However, translation of microbiome findings to clinical practice is challenging. Here, we discuss current knowledge and applications in the field.

METHODS: We revisit some recent advances in the field of faecal microbiome analyses with a focus on covariate analyses and ecological interpretation.

RESULTS: Population-level characterization of gut microbiota variation among healthy volunteers has allowed identifying microbiome covariates required for clinical studies. Currently, microbiome research is moving from relative to quantitative approaches that will shed a new light on microbiota-host interactions in health and disease.

CONCLUSIONS: Covariate characterization and technical advances increase reproducibility of microbiome research. Targeted in vitro/in vivo intervention studies will accelerate clinical implementation of microbiota findings.

RevDate: 2019-02-27

NIH Human Microbiome Portfolio Analysis Team (2019)

A review of 10 years of human microbiome research activities at the US National Institutes of Health, Fiscal Years 2007-2016.

Microbiome, 7(1):31 pii:10.1186/s40168-019-0620-y.

The National Institutes of Health (NIH) is the primary federal government agency for biomedical research in the USA. NIH provides extensive support for human microbiome research with 21 of 27 NIH Institutes and Centers (ICs) currently funding this area through their extramural research programs. This analysis of the NIH extramural portfolio in human microbiome research briefly reviews the early history of this field at NIH, summarizes the program objectives and the resources developed in the recently completed 10-year (fiscal years 2007-2016) $215 M Human Microbiome Project (HMP) program, evaluates the scope and range of the $728 M NIH investment in extramural human microbiome research activities outside of the HMP over fiscal years 2012-2016, and highlights some specific areas of research which emerged from this investment. This analysis closes with a few comments on the technical needs and knowledge gaps which remain for this field to be able to advance over the next decade and for the outcomes of this research to be able to progress to microbiome-based interventions for treating disease and supporting health.

RevDate: 2019-02-27

2017 NIH-wide microbiome workshop writing team (2019)

2017 NIH-wide workshop report on "The Human Microbiome: Emerging Themes at the Horizon of the 21st Century".

Microbiome, 7(1):32 pii:10.1186/s40168-019-0627-4.

The National Institutes of Health (NIH) organized a three-day human microbiome research workshop, August 16-18, 2017, to highlight the accomplishments of the 10-year Human Microbiome Project program, the outcomes of the investments made by the 21 NIH Institutes and Centers which now fund this area, and the technical challenges and knowledge gaps which will need to be addressed in order for this field to advance over the next 10 years. This report summarizes the key points in the talks, round table discussions, and Joint Agency Panel from this workshop.

RevDate: 2019-02-26

Ma Z, L Li (2018)

Semen Microbiome Biogeography: An Analysis Based on a Chinese Population Study.

Frontiers in microbiology, 9:3333.

Investigating inter-subject heterogeneity (or spatial distribution) of human semen microbiome diversity is of important significance. Theoretically, the spatial distribution of biodiversity constitutes the core of microbiome biogeography. Practically, the inter-subject heterogeneity is crucial for understanding the normal (healthy) flora of semen microbiotas as well as their possible changes associated with abnormal fertility. In this article, we analyze the scaling (changes) of semen microbiome diversity across individuals with DAR (diversity-area relationship) analysis, a recent extension to classic SAR (species-area relationship) law in biogeography and ecology. Specifically, the unit of "area" is individual subject, and the microbial diversity in seminal fluid of an individual (area) is assessed via metagenomic DNA sequencing technique and measured in the Hill numbers. The DAR models were then fitted to the accrued diversity across different number of individuals (area size). We further tested the difference in DAR parameters among the healthy, subnormal, and abnormal microbiome samples in terms of their fertility status based on a cross-sectional study of a Chinese cohort. Given that no statistically significant differences in the DAR parameters were detected among the three groups, we built unified DAR models for semen microbiome by combining the healthy, subnormal, and abnormal groups. The model parameters were used to (i) estimate the microbiome diversity scaling in a population (cohort), and construct the so-termed DAR profile; (ii) predict/construct the maximal accrual diversity (MAD) profile in a population; (iii) estimate the pair-wise diversity overlap (PDO) between two individuals and construct the PDO profile; (iv) assess the ratio of individual diversity to population (RIP) accrual diversity. The last item (RIP) is a new concept we propose in this study, which is essentially a ratio of local diversity to regional or global diversity (LRD/LGD), applicable to general biodiversity investigation beyond human microbiome.

RevDate: 2019-02-25

McSkimming DI, Banack HR, Genco R, et al (2019)


American journal of epidemiology pii:5364577 [Epub ahead of print].

RevDate: 2019-02-25

De Filippis F, Pasolli E, Tett A, et al (2019)

Distinct Genetic and Functional Traits of Human Intestinal Prevotella copri Strains Are Associated with Different Habitual Diets.

Cell host & microbe pii:S1931-3128(19)30041-1 [Epub ahead of print].

The role of intestinal Prevotella species in human health is controversial, with both positive and negative associations. Strain-level diversity may contribute to discrepancies in genus and species associations with health and disease. We dissected the gut metagenomes of Italians with varying dietary habits, investigating the presence of distinct Prevotella copri strains. Fiber-rich diets were linked to P. copri types with enhanced potential for carbohydrate catabolism. P. copri strains associated with an omnivore diet had a higher prevalence of the leuB gene-involved in branched-chain amino acid biosynthesis-a risk factor for glucose intolerance and type 2 diabetes. These P. copri pangenomes were compared to existing cohorts, providing evidence of distinct gene repertoires characterizing different P. copri populations, with drug metabolism and complex carbohydrate degradation significantly associated with Western and non-Western individuals, respectively. Strain-level P. copri diversity in gut microbiomes is affected by diet and should be considered when examining host-microbe associations.

RevDate: 2019-02-25

Rogers GB, Ward J, Brown A, et al (2019)

Inclusivity and equity in human microbiome research.

Lancet (London, England), 393(10173):728-729.

RevDate: 2019-02-19

Araos R, EMC D'Agata (2019)

The human microbiota and infection prevention.

Infection control and hospital epidemiology pii:S0899823X1900028X [Epub ahead of print].

The human microbiome participates in numerous aspects of human physiology and disease states. Recently, studies have begun to explore the role of the microbiome in colonization, infection and transmission of pathogens. This review provides a summary of the methodological principles used in microbiome studies and the published evidence of the impact of microbiome dysbiosis in infection prevention.

RevDate: 2019-02-17

Li H, Zhou XY, Yang XR, et al (2019)

Spatial and seasonal variation of the airborne microbiome in a rapidly developing city of China.

The Science of the total environment, 665:61-68 pii:S0048-9697(19)30417-6 [Epub ahead of print].

Exposure to airborne microbes (AM) can affect the human microbiome and has various consequences for human health. Investigating the profiles of AM and the potential bacterial pathogens within, along with the factors influencing their community, is pivotal for understanding the impact of AM on human health. In this study, we collected AM during spring and summer from 11 sites with various levels of urbanization in the city of Xiamen, China. Bacterial community compositions of the AM were determined based on 16S rRNA gene amplicon sequencing. Firmicutes and Proteobacteria were the predominating phyla in the airborne bacterial communities, and a higher (P < 0.05) diversity of AM was found during the summer as compared to the spring. Significant differences in the community structure of the AM and the potential bacterial pathogens within airborne microbes were observed among the seasons and the sites with different levels of urbanization. Increases and/or decreases in the abundance of Bacillus and Acinetobacter could explain a major part of the variations in the AM community compositions. The proportion of potential bacterial pathogens during the summer was significantly higher (P < 0.01) than in the spring, and the relative abundance of several bacterial pathogens (i.e. Burkholderia multivoran, Enterococcus faecium and Streptococcus thermophilus) related to human diseases (39.8% of total pathogens on average) increased with increasing urbanization levels, suggesting that urbanization can increase the AM-associated human health risk.

RevDate: 2019-02-15

Bai J, Jhaney I, Daniel G, et al (2019)

Pilot Study of Vaginal Microbiome Using QIIME 2™ in Women With Gynecologic Cancer Before and After Radiation Therapy.

Oncology nursing forum, 46(2):E48-E59.

OBJECTIVES: To characterize the vaginal microbiome using QIIME 2™ (Quantitative Insights Into Microbial Ecology 2) in women with gynecologic cancer.

SAMPLE &AMP; SETTING: 19 women with gynecologic cancer before and after radiation therapy at a comprehensive cancer center in Atlanta, Georgia.

METHODS &AMP; VARIABLES: This pilot study analyzed vaginal microbiome communities using a microbiome analysis pipeline, beginning with 16S rRNA gene sequencing and processing through use of a bioinformatics pipeline to downstream microbial statistical analysis.

RESULTS: The findings showed the methods to be robust, and most women with gynecologic cancer showed depletion of Lactobacillus. Compared to those pre-radiation therapy, women post-radiation therapy showed higher abundances of Mobiluncus, Atopobium, and Prevotella but lower abundances of Lactobacillus, Gardnerella, and Peptostreptococcus, which are associated with bacterial vaginosis.

IMPLICATIONS FOR NURSING: This study presents the fundamentals of human microbiome data collection and analysis methods to inform nursing science. Assessing the vaginal microbiome provides a potential pathway to develop interventions to ameliorate dysbiosis of the vaginal microbiome.

RevDate: 2019-02-15

Luo Z, Li M, Wu Y, et al (2019)

Systemic translocation of Staphylococcus drives autoantibody production in HIV disease.

Microbiome, 7(1):25 pii:10.1186/s40168-019-0646-1.

BACKGROUND: Increased autoreactive antibodies have been reported in HIV disease; however, the mechanism accounting for autoantibody induction in HIV remains unknown.

RESULTS: Herein, we show that seasonal influenza vaccination induces autoantibody production (e.g., IgG anti-nuclear antibody (ANA) and anti-double-stranded DNA antibody (anti-dsDNA)) in some viral-suppressed antiretroviral therapy (ART)-treated HIV+ subjects, but not in healthy controls. These autoantibodies were not derived from antigen-specific B cells but from activated "bystander" B cells analyzed by single-cell assay and by study of purified polyclonal ANAs from plasma. To explore the mechanism of autoantibody generation in HIV+ subjects, plasma level of microbial products, gene expression profile of B cells, and B cell receptor (BCR) repertoires were analyzed. We found that autoantibody production was associated with increased plasma level of microbial translocation; the patients with high autoantibodies had skewed B cell repertoires and upregulation of genes related to innate immune activation in response to microbial translocation. By analyzing circulating microbial 16S rDNA in plasma, the relative abundance of Staphylococcus was found to be associated with autoantibody production in HIV+ subjects. Finally, we found that injection of heat-killed Staphylococcus aureus promoted germinal center B cell responses and autoantibody production in mice, consistent with the notion that autoantibody production in HIV+ patients is triggered by microbial products.

CONCLUSIONS: Our results showed that translocation of Staphylococcus can promote B cell activation through enhancing germinal center response and induces autoantibody production. It uncovers a potential mechanism linking microbial translocation and autoimmunity in HIV+ disease and provides a strong rationale for targeting Staphylococcus to prevent autoantibody production.

RevDate: 2019-02-14

Shkoporov AN, C Hill (2019)

Bacteriophages of the Human Gut: The "Known Unknown" of the Microbiome.

Cell host & microbe, 25(2):195-209.

The human gut microbiome is a dense and taxonomically diverse consortium of microorganisms. While the bacterial components of the microbiome have received considerable attention, comparatively little is known about the composition and physiological significance of human gut-associated bacteriophage populations (phageome). By extrapolating our knowledge of phage-host interactions from other environments, one could expect that >1012 viruses reside in the human gut, and we can predict that they play important roles in regulating the complex microbial networks operating in this habitat. Before delving into their function, we need to first overcome the challenges associated with studying and characterizing the phageome. In this Review, we summarize the available methods and main findings regarding taxonomic composition, community structure, and population dynamics in the human gut phageome. We also discuss the main challenges in the field and identify promising avenues for future research.

RevDate: 2019-02-14

Reddel S, Putignani L, F Del Chierico (2019)

The Impact of Low-FODMAPs, Gluten-Free, and Ketogenic Diets on Gut Microbiota Modulation in Pathological Conditions.

Nutrients, 11(2): pii:nu11020373.

The gut microbiota performs several essential protective, structural, and metabolic functions for host health. The maintenance of a beneficial microbiota requires a homeostatic equilibrium within microbial communities, and between the microorganisms and the host. The gut microbiota composition may be affected by external factors, among them diet habits may be considered most important. In some pathological conditions such as irritable bowel syndrome (IBS), celiac disease (CD), or neurological disorders (ND), specific dietary regimens as low-fermentable, oligo-, di-, mono-saccharides and polyols (FODMAPs), ketogenic (KD), and gluten-free (GFD) diets are considered therapeutic. These kinds of diets are characterized by a reduction or exclusion of a specific nutrient from the entire dietary pattern. Despite these alimentary regimens showing beneficial effects on disease symptoms, they can affect microbiota composition, especially if they are protracted for a long time. To date, only a few studies have reported the effects of these diets on gut microbiota. In this review, we discuss the effects of low-FODMAPs, KD, and GFD on gut microbiota modulation in pathological conditions, advancing the possibility of depicting a balanced diet and developing personalized dietary intervention protocols.

RevDate: 2019-02-12

Blakeley-Ruiz JA, Erickson AR, Cantarel BL, et al (2019)

Metaproteomics reveals persistent and phylum-redundant metabolic functional stability in adult human gut microbiomes of Crohn's remission patients despite temporal variations in microbial taxa, genomes, and proteomes.

Microbiome, 7(1):18 pii:10.1186/s40168-019-0631-8.

BACKGROUND: The gut microbiome plays a fundamental role in the human host's overall health by contributing key biological functions such as expanded metabolism and pathogen defense/immune control. In a healthy individual, the gut microbiome co-exists within the human host in a symbiotic, non-inflammatory relationship that enables mutual benefits, such as microbial degradation of indigestible food products into small molecules that the host can utilize, and enhanced pathogen defense. In abnormal conditions, such as Crohn's disease, this favorable metabolic relationship breaks down and a variety of undesirable activities result, including chronic inflammation and other health-related issues. It has been difficult, however, to elucidate the overall functional characteristics of this relationship because the microbiota can vary substantially in composition for healthy humans and possibly even more in individuals with gut disease conditions such as Crohn's disease. Overall, this suggests that microbial membership composition may not be the best way to characterize a phenotype. Alternatively, it seems to be more informative to examine and characterize the functional composition of a gut microbiome. Towards that end, this study examines 25 metaproteomes measured in several Crohn's disease patients' post-resection surgery across the course of 1 year, in order to examine persistence of microbial taxa, genes, proteins, and metabolic functional distributions across time in individuals whose microbiome might be more variable due to the gut disease condition.

RESULTS: The measured metaproteomes were highly personalized, with all the temporally-related metaproteomes clustering most closely by individual. In general, the metaproteomes were remarkably distinct between individuals and to a lesser extent within individuals. This prompted a need to characterize the metaproteome at a higher functional level, which was achieved by annotating identified protein groups with KEGG orthologous groups to infer metabolic modules. At this level, similar and redundant metabolic functions across multiple phyla were observed across time and between individuals. Tracking through these various metabolic modules revealed a clear path from carbohydrate, lipid, and amino acid degradation to central metabolism and finally the production of fermentation products.

CONCLUSIONS: The human gut metaproteome can vary quite substantially across time and individuals. However, despite substantial intra-individual variation in the metaproteomes, there is a clear persistence of conserved metabolic functions across time and individuals. Additionally, the persistence of these core functions is redundant across multiple phyla but is not always observable in the same sample. Finally, the gut microbiome's metabolism is not driven by a set of discrete linear pathways but a web of interconnected reactions facilitated by a network of enzymes that connect multiple molecules across multiple pathways.

RevDate: 2019-02-10

Marsh RL, Smith-Vaughan HC, Chen ACH, et al (2019)

Multiple Respiratory Microbiota Profiles Are Associated With Lower Airway Inflammation in Children With Protracted Bacterial Bronchitis.

Chest pii:S0012-3692(19)30010-8 [Epub ahead of print].

BACKGROUND: Effective management of protracted bacterial bronchitis (PBB) is needed to prevent chronic disease (eg, bronchiectasis). Understanding the contributions of ongoing airway infection and inflammation is important to achieving optimal PBB treatments. The aim of this study was to compare BAL microbiota, bacterial biomass, and inflammatory markers in children with PBB and age-matched control patients.

METHODS: BAL was prospectively collected from 28 children with PBB (median age, 1.7 years; range, 0.6-7.4) and 8 control patients (median age, 1.9 years; range, 0.4-4.7). BAL microbiology was determined using culture, 16S ribosomal RNA gene sequencing and bacterial biomass quantification. BAL inflammatory cells, IL-8, and IL-1β were used to assess lower airway inflammation.

RESULTS: Bacterial biomass, neutrophil percentage, IL-8, and IL-1β levels were significantly higher in children with PBB compared with control patients. BAL microbiota in children with PBB was significantly different to that of control patients (permutational analysis of variance P = .001) and clustered into four distinct profiles that were either dominated by a respiratory pathogen or contained a more diverse microbiota including Prevotella species. Alpha diversity was unrelated to bacterial biomass, culture of recognized respiratory pathogens, or inflammatory markers.

CONCLUSIONS: Neutrophilic inflammation in children with PBB was associated with multiple BAL microbiota profiles. Significant associations between inflammatory markers and bacterial biomass, but not alpha diversity, suggest that inflammation in children with PBB is not driven by single pathogenic species. Understanding the role of the entire respiratory microbiota in PBB pathogenesis may be important to determining whether bacteria other than the recognized pathogens contribute to disease recurrence and progression to bronchiectasis.

RevDate: 2019-02-08

Healy CM, GP Moran (2019)

The microbiome and oral cancer: More questions than answers.

Oral oncology, 89:30-33.

Recent advances in DNA sequencing technology have facilitated rapid advances in the analysis of the human microbiome and its role in human disease. Several studies have now shown that OSCC and some oral premalignant conditions are associated with alterations in the oral microbiome. These studies raise questions regarding the role of the oral microbiome in the progression of oral malignancies and whether microbiome change is a significant risk factor in the development of oral cancer. This short review summarises current knowledge in the field and highlights questions that require further investigation.

RevDate: 2019-02-07

Bekker V, Zwittink RD, Knetsch CW, et al (2019)

Dynamics of the Gut Microbiota in Children Receiving Selective or Total Gut Decontamination Treatment During Hematopoietic Stem Cell Transplantation.

Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation pii:S1083-8791(19)30095-3 [Epub ahead of print].

Bloodstream infections and Graft-versus-Host disease (GvHD) are common complications after hematopoietic stem cell transplantation (HSCT) procedures, associated with the gut microbiota which acts as a reservoir for opportunistic pathogens. Selective gut decontamination (SGD) and total gut decontamination (TGD) during HSCT have been associated with a decreased risk of developing these complications after transplantation. However, since studies have shown conflicting results, the use of these treatments remain subject of debate. In addition, their impact on the gut microbiota is not well studied. The aim of this study was to elucidate the dynamics of the microbiota during and after TGD and to compare these to the dynamics of SGD. In this prospective, observational, single-center study, fecal samples were longitudinally collected from nineteen children eligible for allogenic HSCT (TGD n=12, SGD n=7), weekly during hospital admission and monthly after discharge. In addition, fecal samples were collected from three family stem cell donors. Fecal microbiota structure of patients and donors was determined by 16S rRNA gene amplicon sequencing. Microbiota richness and diversity markedly decreased during SGD and TGD and gradually increased after cessation of decontamination treatment. During SGD, gut microbiota composition was relatively stable and dominated by Bacteroides, while it showed high inter- and intra-individual variation and low Bacteroides abundance during TGD. In some children, TGD allowed the genera Enterococcus and Streptococcus to thrive during treatment. A gut microbiota dominated by Bacteroides was associated with increased predicted activity of several metabolic processes. Comparing the microbiota of recipients and their donors indicated that receiving a stem cell transplant did not alter the patient's microbiota to become more similar to that of its donor. Overall, our findings indicate that SGD and TGD affect gut microbiota structure in a treatment-specific manner. Whether these treatments affect clinical outcomes via interference with the gut microbiota needs to be further elucidated.

RevDate: 2019-02-07

Lu H, Ren Z, Li A, et al (2019)

Tongue coating microbiome data distinguish patients with pancreatic head cancer from healthy controls.

Journal of oral microbiology, 11(1):1563409 pii:1563409.

Background: The microbiota plays a critical role in the process of human carcinogenesis. Pancreatic head carcinoma (PHC)-associated tongue coating microbiome dysbiosis has not yet been clearly defined.Objective: Our aim is to reveal the bacterial composition shifts in the microbiota of the tongue coat of PHC patients.Design: The tongue coating microbiota was analyzed in 30 PHC patients and 25 healthy controls using 16S rRNA gene sequencing technology.Results: The microbiome diversity of the tongue coat in PHC patients was significantly increased, as shown by the Shannon, Simpson, inverse Simpson, Obs and incidence-based coverage estimators. Principal component analysis revealed that PHC patients were colonized by remarkably different tongue coating microbiota than healthy controls and liver cancer patients. Linear discriminant analysis effect size revealed that Leptotrichia, Fusobacterium,Rothia, Actinomyces, Corynebacterium, Atopobium, Peptostreptococcus, Catonella, Oribacterium, Filifactor, Campylobacter, Moraxella and Tannerella were overrepresented in the tongue coating of PHC patients, and Haemophilus, Porphyromonas and Paraprevotella were enriched in the tongue coating microbiota of healthy controls. Strikingly, Haemophilus, Porphyromonas, Leptotrichia and Fusobacterium could distinguish PHC patients from healthy subjects, and Streptococcus and SR1 could distinguish PHC patients from liver cancer patients. Conclusions: These findings identified the microbiota dysbiosis of the tongue coat in PHC patients, and provide insight into the association between the human microbiome and pancreatic cancer.

RevDate: 2019-02-06

Morales E, Chen J, KL Greathouse (2019)

Compositional Analysis of the Human Microbiome in Cancer Research.

Methods in molecular biology (Clifton, N.J.), 1928:299-335.

Gut microbial composition has shown to be associated with obesity, diabetes mellitus, inflammatory bowel disease, colitis, autoimmune disorders, and cancer, among other diseases. Microbiome research has significantly evolved through the years and continues to advance as we develop new and better strategies to more accurately measure its composition and function. Careful selection of study design, inclusion and exclusion criteria of participants, and methodology are paramount to accurately analyze microbial structure. Here we present the most up-to-date available information on methods for gut microbial collection and analysis.

RevDate: 2019-02-05

Forster SC, Kumar N, Anonye BO, et al (2019)

A human gut bacterial genome and culture collection for improved metagenomic analyses.

Nature biotechnology, 37(2):186-192.

Understanding gut microbiome functions requires cultivated bacteria for experimental validation and reference bacterial genome sequences to interpret metagenome datasets and guide functional analyses. We present the Human Gastrointestinal Bacteria Culture Collection (HBC), a comprehensive set of 737 whole-genome-sequenced bacterial isolates, representing 273 species (105 novel species) from 31 families found in the human gastrointestinal microbiota. The HBC increases the number of bacterial genomes derived from human gastrointestinal microbiota by 37%. The resulting global Human Gastrointestinal Bacteria Genome Collection (HGG) classifies 83% of genera by abundance across 13,490 shotgun-sequenced metagenomic samples, improves taxonomic classification by 61% compared to the Human Microbiome Project (HMP) genome collection and achieves subspecies-level classification for almost 50% of sequences. The improved resource of gastrointestinal bacterial reference sequences circumvents dependence on de novo assembly of metagenomes and enables accurate and cost-effective shotgun metagenomic analyses of human gastrointestinal microbiota.

RevDate: 2019-02-02

Du Toit A (2019)

Expanding diversity of the human microbiome.

Nature reviews. Microbiology pii:10.1038/s41579-019-0154-0 [Epub ahead of print].

RevDate: 2019-02-01

Whittle E, Leonard MO, Harrison R, et al (2018)

Multi-Method Characterization of the Human Circulating Microbiome.

Frontiers in microbiology, 9:3266.

The term microbiome describes the genetic material encoding the various microbial populations that inhabit our body. Whilst colonization of various body niches (e.g., the gut) by dynamic communities of microorganisms is now universally accepted, the existence of microbial populations in other "classically sterile" locations, including the blood, is a relatively new concept. The presence of bacteria-specific DNA in the blood has been reported in the literature for some time, yet the true origin of this is still the subject of much deliberation. The aim of this study was to investigate the phenomenon of a "blood microbiome" by providing a comprehensive description of bacterially derived nucleic acids using a range of complementary molecular and classical microbiological techniques. For this purpose we utilized a set of plasma samples from healthy subjects (n = 5) and asthmatic subjects (n = 5). DNA-level analyses involved the amplification and sequencing of the 16S rRNA gene. RNA-level analyses were based upon the de novo assembly of unmapped mRNA reads and subsequent taxonomic identification. Molecular studies were complemented by viability data from classical aerobic and anaerobic microbial culture experiments. At the phylum level, the blood microbiome was predominated by Proteobacteria, Actinobacteria, Firmicutes, and Bacteroidetes. The key phyla detected were consistent irrespective of molecular method (DNA vs. RNA), and consistent with the results of other published studies. In silico comparison of our data with that of the Human Microbiome Project revealed that members of the blood microbiome were most likely to have originated from the oral or skin communities. To our surprise, aerobic and anaerobic cultures were positive in eight of out the ten donor samples investigated, and we reflect upon their source. Our data provide further evidence of a core blood microbiome, and provide insight into the potential source of the bacterial DNA/RNA detected in the blood. Further, data reveal the importance of robust experimental procedures, and identify areas for future consideration.

RevDate: 2019-01-31

Leviatan S, E Segal (2019)

A Significant Expansion of Our Understanding of the Composition of the Human Microbiome.

mSystems, 4(1): pii:mSystems00010-19.

Shotgun sequencing of samples taken from the human microbiome often reveals only partial mapping of the sequenced metagenomic reads to existing reference genomes. Such partial mappability indicates that many genomes are missing in our reference genome set. This is particularly true for non-Western populations and for samples that do not originate from the gut. Pasolli et al. (E. Pasolli, F. Asnicar, S. Manara, M. Zolfo, et al., Cell, 2019, perform a grand effort to expand the reference set, and to better classify its members, revealing a wider pangenome of existing species as well as identifying new species of previously unknown taxonomic branches.

RevDate: 2019-01-31

Tejesvi MV, Nissi R, Saravesi K, et al (2019)

Association of prevalent vaginal microbiome of mother with occurrence of type I diabetes in child.

Scientific reports, 9(1):959 pii:10.1038/s41598-018-37467-w.

Type I diabetes (T1D) is a rapidly increasing autoimmune disease especially in the Western countries and poses a serious global health problem. Incidence of T1D cannot be fully explained by genetic background, and environmental factors have been assumed to play a role. Environmental conditions and composition of human microbiome have been found to correlate with the incidence of T1D. We asked whether mothers' prevalent vaginal microbiome could correlate with the incidence of T1D in child. To test this hypothesis, we collected samples of vaginal microbiomes from eight mothers that had at least one child with T1D (child age maximum of 11 years at the time of sampling), born with a vaginal delivery. Eight control mothers had child/children with vaginal delivery and no diabetic child/children. The microbiomes were studied by using 16S rRNA Ion Torrent high throughput sequencing. We found that composition of total and Lactobacillus microbiome was altered, and saw an indication that diversity of vaginal microbiomes of the mothers with a diabetic child could be higher. Based on these pilot observations, we strongly encourage a larger population study to verify whether mother vaginal microbiome diversity and composition are linked to the prevalence of T1D in children.

RevDate: 2019-01-30

Naradasu D, Miran W, Sakamoto M, et al (2018)

Isolation and Characterization of Human Gut Bacteria Capable of Extracellular Electron Transport by Electrochemical Techniques.

Frontiers in microbiology, 9:3267.

Microorganisms are known to exhibit extracellular electron transfer (EET) in a wide variety of habitats. However, as for the human microbiome which significantly impacts our health, the role and importance of EET has not been widely investigated. In this study, we enriched and isolated the EET-capable bacteria from human gut microbes using an electrochemical enrichment method and examined whether the isolates couple EET with anaerobic respiration or fermentation. Upon the use of energy-rich or minimum media (with acetate or lactate) for electrochemical enrichment with the human gut sample at an electrode potential of +0.4 V [vs. the standard hydrogen electrode (SHE)], both culture conditions showed significant current production. However, EET-capable pure strains were enriched specifically with minimum media, and subsequent incubation using the δ-MnO2-agar plate with lactate or acetate led to the isolation of two EET-capable microbial strains, Gut-S1 and Gut-S2, having 99% of 16S rRNA gene sequence identity with Enterococcus avium (E. avium) and Klebsiella pneumoniae (K. pneumoniae), respectively. While the enrichment involved anaerobic respiration with acetate and lactate, further electrochemistry with E. avium and K. pneumoniae revealed that the glucose fermentation was also coupled with EET. These results indicate that EET couples not only with anaerobic respiration as found in environmental bacteria, but also with fermentation in the human gut.

RevDate: 2019-01-29

Devoto AE, Santini JM, Olm MR, et al (2019)

Megaphages infect Prevotella and variants are widespread in gut microbiomes.

Nature microbiology pii:10.1038/s41564-018-0338-9 [Epub ahead of print].

Bacteriophages (phages) dramatically shape microbial community composition, redistribute nutrients via host lysis and drive evolution through horizontal gene transfer. Despite their importance, much remains to be learned about phages in the human microbiome. We investigated the gut microbiomes of humans from Bangladesh and Tanzania, two African baboon social groups and Danish pigs; many of these microbiomes contain phages belonging to a clade with genomes >540 kilobases in length, the largest yet reported in the human microbiome and close to the maximum size ever reported for phages. We refer to these as Lak phages. CRISPR spacer targeting indicates that Lak phages infect bacteria of the genus Prevotella. We manually curated to completion 15 distinct Lak phage genomes recovered from metagenomes. The genomes display several interesting features, including use of an alternative genetic code, large intergenic regions that are highly expressed and up to 35 putative transfer RNAs, some of which contain enigmatic introns. Different individuals have distinct phage genotypes, and shifts in variant frequencies over consecutive sampling days reflect changes in the relative abundance of phage subpopulations. Recent homologous recombination has resulted in extensive genome admixture of nine baboon Lak phage populations. We infer that Lak phages are widespread in gut communities that contain the Prevotella species, and conclude that megaphages, with fascinating and underexplored biology, may be common but largely overlooked components of human and animal gut microbiomes.

RevDate: 2019-01-28

Waldron L, Schiffer L, Azhar R, et al (2019)

Improving Accessibility of the Human Microbiome Project Data Through Integration With R/Bioconductor.

American journal of epidemiology pii:5299225 [Epub ahead of print].

RevDate: 2019-01-28

Woods DF, Kozak IM, Flynn S, et al (2018)

The Microbiome of an Active Meat Curing Brine.

Frontiers in microbiology, 9:3346.

Traditional food products are important to our culture and heritage, and to the continued success of the food industry. Many of the production processes associated with these products have not been subjected to an in-depth microbial compositional analysis. The traditional process of curing meat, both preserves a natural protein source, as well as increasing its organoleptic qualities. One of the most important salting processes is known as Wiltshire curing. The Wiltshire process involves injecting pork with a curing solution and immersing the meat into microbial-rich brine which promotes the development of the distinct organoleptic characteristics. The important microbial component of Wiltshire brine has not been extensively characterized. We analyzed the key microbial component of Wiltshire brine by performing microbiome analysis using Next Generation Sequencing (NGS) technologies. This analysis identified the genera, Marinilactibacillus, Carnobacterium, Leuconostoc, and Vibrio as the core microflora present in Wiltshire curing brine. The important food industrial applications of these bacteria were also assessed. The bacterial diversity of the brine was investigated, and the community composition of the brine was demonstrated to change over time. New knowledge on the characterization of key microbiota associated with a productive Wiltshire brine is an important development linked to promoting enhanced quality and safety of meat processing in the food industry.

RevDate: 2019-01-28

Forbes JD, Bernstein CN, Tremlett H, et al (2018)

A Fungal World: Could the Gut Mycobiome Be Involved in Neurological Disease?.

Frontiers in microbiology, 9:3249.

The human microbiome has received decades of attention from scientific and medical research communities. The human gastrointestinal tract is host to immense populations of microorganisms including bacteria, viruses, archaea, and fungi (the gut microbiota). High-throughput sequencing and computational advancements provide unprecedented ability to investigate the structure and function of microbial communities associated with the human body in health and disease. Most research to date has largely focused on elucidating the bacterial component of the human gut microbiota. Study of the gut "mycobiota," which refers to the diverse array of fungal species, is a relatively new and rapidly progressing field. Though omnipresent, the number and abundance of fungi occupying the human gut is orders of magnitude smaller than that of bacteria. Recent insights however, have suggested that the gut mycobiota may be intricately linked to health and disease. Evaluation of the gut mycobiota has shown that not only are the fungal communities altered in disease, but they also play a role in maintaining intestinal homeostasis and influencing systemic immunity. In addition, it is now widely accepted that host-fungi and bacteria-fungi associations are critical to host health. While research of the gut mycobiota in health and disease is on the rise, little research has been performed in the context of neuroimmune and neurodegenerative conditions. Gut microbiota dysbiosis (specifically bacteria and archaea) have been reported in neurological diseases such as multiple sclerosis, amyotrophic lateral sclerosis, and Alzheimer's, among others. Given the widely accepted bacteria-fungi associations and paucity of mycobiota-specific studies in neurological disease, this review discusses the potential role fungi may play in multiple sclerosis and other neurological diseases. Herein, we provide an overview of recent advances in gut mycobiome research and discuss the plausible role of both intestinal and non-intestinal fungi in the context of neuroimmune and neurodegenerative conditions.

RevDate: 2019-01-25

Brasili E, Hassimotto NMA, Del Chierico F, et al (2019)

Daily Consumption of Orange Juice from Citrus sinensis L. Osbeck cv. Cara Cara and cv. Bahia Differently Affects Gut Microbiota Profiling as Unveiled by an Integrated Meta-Omics Approach.

Journal of agricultural and food chemistry [Epub ahead of print].

We have investigated the effect of intake of two different orange juices from Citrus sinensis cv. "Cara Cara" and cv. "Bahia" on faecal microbiota and metabolome using an integrated meta-omics approach. Following a randomized crossover design, healthy subjects daily consumed 500 mL of orange juice from Cara Cara or Bahia juices or an isocaloric control drink. Stools were collected at baseline (T0) and after a week (T7) of intervention. Operational taxonomic units (OTUs) were pyrosequenced targeting 16S rRNA, and faecal metabolites were analyzed by an untargeted metabolomics approach based on 1H NMR spectroscopy. The major shift observed in microbiota composition after orange juice intake was the increased abundance of a network of Clostridia OTUs from Mogibacteriaceae, Tissierellaceae, Veillonellaceae, Odoribacteraceae, and Ruminococcaceae families, whose members were differently affected by Cara Cara or Bahia juice consumption. A core of six metabolites such as inositol, choline, lysine, arginine, urocanic acid, and formate significantly increased in Cara Cara compared to the Bahia group.

RevDate: 2019-01-24

Tanoue T, Morita S, Plichta DR, et al (2019)

A defined commensal consortium elicits CD8 T cells and anti-cancer immunity.

Nature pii:10.1038/s41586-019-0878-z [Epub ahead of print].

There is a growing appreciation for the importance of the gut microbiota as a therapeutic target in various diseases. However, there are only a handful of known commensal strains that can potentially be used to manipulate host physiological functions. Here we isolate a consortium of 11 bacterial strains from healthy human donor faeces that is capable of robustly inducing interferon-γ-producing CD8 T cells in the intestine. These 11 strains act together to mediate the induction without causing inflammation in a manner that is dependent on CD103+ dendritic cells and major histocompatibility (MHC) class Ia molecules. Colonization of mice with the 11-strain mixture enhances both host resistance against Listeria monocytogenes infection and the therapeutic efficacy of immune checkpoint inhibitors in syngeneic tumour models. The 11 strains primarily represent rare, low-abundance components of the human microbiome, and thus have great potential as broadly effective biotherapeutics.

RevDate: 2019-01-23

Zhang C, Thakkar PV, Powell SE, et al (2018)

A Comparison of Homogenization vs. Enzymatic Lysis for Microbiome Profiling in Clinical Endoscopic Biopsy Tissue Samples.

Frontiers in microbiology, 9:3246.

Identification of the human microbiome has proven to be of utmost importance with the emerging role of bacteria in various physiological and pathological processes. High throughput sequencing strategies have evolved to assess the composition of the microbiome. To identify possible bias that may exist in the processing of tissue for whole genome sequencing (WGS), it is important to evaluate the extraction method on the overall microbial content and composition. Here we compare two different methods of extraction, homogenization vs. enzymatic lysis, on gastric, esophageal and colorectal biopsies and survey the microbial content and composition using WGS and quantitative PCR (qPCR). We examined total bacterial content using universal 16S rDNA qPCR as well as the abundance of three phyla (Actinobacter, Firmicutes, Bacteroidetes) and one genus (Fusobacterium). We found minimal differences between the two extraction methods in the overall community structure. Furthermore, based on our qPCR analysis, neither method demonstrated preferential extraction of any particular clade of bacteria, nor significantly altered the detection of Gram-positive or Gram-negative organisms. However, although the overall microbial composition remained very similar and the most prevalent bacteria could be detected effectively using either method, the precise community structure and microbial abundances between the two methods were different, primarily due to variations in detection of low abundance genus. We also demonstrate that the homogenization extraction method provides higher microbial DNA content and higher read counts from human tissue biopsy samples of the gastrointestinal tract.

RevDate: 2019-01-23

Dominguez-Bello MG, Godoy-Vitorino F, Knight R, et al (2019)

Role of the microbiome in human development.

Gut pii:gutjnl-2018-317503 [Epub ahead of print].

The host-microbiome supraorganism appears to have coevolved and the unperturbed microbial component of the dyad renders host health sustainable. This coevolution has likely shaped evolving phenotypes in all life forms on this predominantly microbial planet. The microbiota seems to exert effects on the next generation from gestation, via maternal microbiota and immune responses. The microbiota ecosystems develop, restricted to their epithelial niches by the host immune system, concomitantly with the host chronological development, providing early modulation of physiological host development and functions for nutrition, immunity and resistance to pathogens at all ages. Here, we review the role of the microbiome in human development, including evolutionary considerations, and the maternal/fetal relationships, contributions to nutrition and growth. We also discuss what constitutes a healthy microbiota, how antimicrobial modern practices are impacting the human microbiota, the associations between microbiota perturbations, host responses and diseases rocketing in urban societies and potential for future restoration.

RevDate: 2019-01-22

Bilen M, Fonkou MDM, Caputo A, et al (2018)

Phoenicibacter congonensis gen. nov., sp. nov., a new genus isolated from the human gut and its description using a taxonogenomic approach.

Antonie van Leeuwenhoek pii:10.1007/s10482-018-01211-1 [Epub ahead of print].

Culturomics has recently allowed the isolation and description of previously uncultured bacteria from the human microbiome at different body sites. As part of a project aiming to describe the human gut microbiota by culturomics, Phoenicibacter congonensis strain Marseille-P3241T was isolated from the gut of a 45 years old Pygmy female. In the present work, we aim to describe this strain via the taxonogenomics approach. The major phenotypic, genomic and biochemical characteristics of this strain were analysed. Strain Marseille-P3241T is an anaerobic, Gram-positive and motile coccobacillus that grows optimally at 37 °C. The genome of strain Marseille-P3241T is 1,447,956 bp long with 43.44% GC content and its 16S rRNA gene sequence exhibited 89% sequence similarity with that of Denitrobacterium detoxificans strain NPOH1T, the phylogenetically closest related species with current standing in nomenclature. After performing a phylogenetic and genomic analysis, we conclude that strain Marseille-P3241T (= CCUG 70681T = CSUR P3241T) represents the type species of a new genus, for which we propose the name Phoenicibacter congonensis gen. nov., sp. nov.

RevDate: 2019-01-22

Malla MA, Dubey A, Kumar A, et al (2018)

Exploring the Human Microbiome: The Potential Future Role of Next-Generation Sequencing in Disease Diagnosis and Treatment.

Frontiers in immunology, 9:2868.

The interaction between the human microbiome and immune system has an effect on several human metabolic functions and impacts our well-being. Additionally, the interaction between humans and microbes can also play a key role in determining the wellness or disease status of the human body. Dysbiosis is related to a plethora of diseases, including skin, inflammatory, metabolic, and neurological disorders. A better understanding of the host-microbe interaction is essential for determining the diagnosis and appropriate treatment of these ailments. The significance of the microbiome on host health has led to the emergence of new therapeutic approaches focused on the prescribed manipulation of the host microbiome, either by removing harmful taxa or reinstating missing beneficial taxa and the functional roles they perform. Culturing large numbers of microbial taxa in the laboratory is problematic at best, if not impossible. Consequently, this makes it very difficult to comprehensively catalog the individual members comprising a specific microbiome, as well as understanding how microbial communities function and influence host-pathogen interactions. Recent advances in sequencing technologies and computational tools have allowed an increasing number of metagenomic studies to be performed. These studies have provided key insights into the human microbiome and a host of other microbial communities in other environments. In the present review, the role of the microbiome as a therapeutic agent and its significance in human health and disease is discussed. Advances in high-throughput sequencing technologies for surveying host-microbe interactions are also discussed. Additionally, the correlation between the composition of the microbiome and infectious diseases as described in previously reported studies is covered as well. Lastly, recent advances in state-of-the-art bioinformatics software, workflows, and applications for analysing metagenomic data are summarized.

RevDate: 2019-01-21

Lauwers L, Bastiaens H, Remmen R, et al (2019)

The Integration of Interlinkages Between Nature and Human Health in Primary Health Care: Protocol for a Scoping Review.

JMIR research protocols, 8(1):e12510 pii:v8i1e12510.

BACKGROUND: International overview reports and the majority of scientific publications on interlinkages between nature and human health (NHI) do not seem to focus on the role of the health care sector. Primary health care (PHC) is often the first point of contact people have with the health care system and provides comprehensive, accessible, and community-based care that meets the health needs of individuals throughout their life. PHC is a vital backbone for linking knowledge and practice within the organization of health care. This scoping review aims to focus on the potential role of PHC in relation to NHI.

OBJECTIVE: The objective of this protocol is to present the method used to scope international overview reports and scientific publications on what is mentioned on the integration of NHI in PHC.

METHODS: The international overview reports have been screened for keywords relating to PHC. We developed a specific search strategy to scope scientific literature on NHI in relation to PHC. The scientific literature search ran in Web of Science (WOS) and PubMed from inception to May 2017. The scientific publications are screened by 2 independent reviewers, which will result in a list of relevant publications that meet eligibility and inclusion criteria.

RESULTS: On the basis of a first screen on the title of the first 200 results in both search engines, we decided to restrict to WOS. First insights in the international overview reports and the quantitative overview of the results in WOS give a first impression of a missing link between NHI and PHC. The findings are expected to identify knowledge gaps in the translation of evidence on NHI in PHC practices and the role of PHC regarding the application of that evidence in health care practice.

CONCLUSIONS: This is, to our knowledge, the first study that seeks to relate existing knowledge on NHI to PHC. The presentation of our method through this protocol allows researchers to build upon and improve our work in future research on the practical implementation of NIH. The findings of the scoping review are expected to guide future scientific research, international policy directives, and PHC workers to fill the gaps in the integration of NHI in PHC.


RevDate: 2019-01-21

Joris BR, GB Gloor (2019)

Unaccounted risk of cardiovascular disease: the role of the microbiome in lipid metabolism.

Current opinion in lipidology [Epub ahead of print].

PURPOSE OF REVIEW: Not all of the risk of cardiovascular disease can be explained by diet and genetics, and the human microbiome, which lies at the interface of these two factors, may help explain some of the unaccounted risk. This review examines some of the well established links between the microbiome and cardiovascular health, and proposes relatively unexplored associations.

RECENT FINDINGS: Byproducts of microbial metabolism are associated with health and disease: Trimethylamine N oxide is associated with atherosclerosis; whereas short-chain fatty acids are associated with decreased inflammation and increased energy expenditure. More broadly, a large number of association studies have been conducted to explore the connections between bacterial taxa and metabolic syndrome. In contrast, the relationship between the microbiome and triglycerides levels remains poorly understood.

SUMMARY: We suggest that deeper understanding of the molecular mechanisms that drive linkages between the microbiome and disease can be determined by replacing 16S rRNA gene sequencing with shotgun metagenomic sequencing or other functional approaches. Furthermore, to ensure translatability and reproducibility of research findings, a combination of multiple different complementary '-omic' approaches should be employed.

RevDate: 2019-01-21

Pasolli E, Asnicar F, Manara S, et al (2019)

Extensive Unexplored Human Microbiome Diversity Revealed by Over 150,000 Genomes from Metagenomes Spanning Age, Geography, and Lifestyle.

Cell pii:S0092-8674(19)30001-7 [Epub ahead of print].

The body-wide human microbiome plays a role in health, but its full diversity remains uncharacterized, particularly outside of the gut and in international populations. We leveraged 9,428 metagenomes to reconstruct 154,723 microbial genomes (45% of high quality) spanning body sites, ages, countries, and lifestyles. We recapitulated 4,930 species-level genome bins (SGBs), 77% without genomes in public repositories (unknown SGBs [uSGBs]). uSGBs are prevalent (in 93% of well-assembled samples), expand underrepresented phyla, and are enriched in non-Westernized populations (40% of the total SGBs). We annotated 2.85 M genes in SGBs, many associated with conditions including infant development (94,000) or Westernization (106,000). SGBs and uSGBs permit deeper microbiome analyses and increase the average mappability of metagenomic reads from 67.76% to 87.51% in the gut (median 94.26%) and 65.14% to 82.34% in the mouth. We thus identify thousands of microbial genomes from yet-to-be-named species, expand the pangenomes of human-associated microbes, and allow better exploitation of metagenomic technologies.

RevDate: 2019-01-18

Pellock SJ, Walton WG, Ervin SM, et al (2019)

Discovery and Characterization of FMN-Binding β-Glucuronidases in the Human Gut Microbiome.

Journal of molecular biology pii:S0022-2836(19)30011-7 [Epub ahead of print].

The human gut microbiota encodes β-glucuronidases (GUS) that play key roles in health and disease via the metabolism of glucuronate-containing carbohydrates and drugs. Hundreds of putative bacterial GUS enzymes have been identified by metagenomic analysis of the human gut microbiome, but less than 10% have characterized structures and functions. Here we describe a set of unique gut microbial GUS enzymes that bind flavin mononucleotide (FMN). First, we show using mass spectrometry, isothermal titration calorimetry, and x-ray crystallography that a purified GUS from the gut commensal microbe Faecalibacterium prausnitzii binds to FMN on a surface groove located 30 Å away from the active site. Second, utilizing structural and functional data from this FMN-binding GUS, we analyzed the 279 unique GUS sequences from the human microbiome project database and identified 14 putative FMN-binding GUSs. We characterized four of these hits and solved the structure of two, the GUSs from Ruminococcus gnavus and Roseburia hominis, which confirmed that these are FMN binders. Third, binding and kinetic analysis of the FMN-binding site mutants of these five GUSs show that they utilize a conserved site to bind FMN that is not essential for GUS activity, but can affect KM. Lastly, a comprehensive structural review of the PDB reveals that the FMN-binding site employed by these enzymes is unlike any structurally characterized FMN-binders to date. These findings reveal the first instance of an FMN-binding glycoside hydrolase and suggest a potential link between FMN and carbohydrate metabolism in the human gut microbiota.

RevDate: 2019-01-18

Espin-Garcia O, Croitoru K, W Xu (2019)

A finite mixture model for X-chromosome association with an emphasis on microbiome data analysis.

Genetic epidemiology [Epub ahead of print].

Analysis of the X chromosome has been largely neglected in genetic studies mainly because of complex underlying biological mechanisms. On the other hand, the study of human microbiome data (typically over-dispersed counts with an excess of zeros) has generated great interest recently because of advancements in next-generation sequencing technologies. We propose a novel approach to infer the association between host genetic variants in the X-chromosome and microbiome data. The method accounts for random X-chromosome inactivation (XCI), skewed (or nonrandom) XCI (XCI-S), and escape of XCI (XCI-E). The inference is performed through a finite mixture model (FMM), in which an indicator variable denoting the "true" biological mechanism is treated as missing data. An expectation-maximization algorithm on zero-inflated and two-part models is implemented to estimate genetic effects. We investigate the performance of the FMM along with strategies that assume XCI and XCI-E mechanisms for all subjects compared with alternative approaches. Briefly, an XCI mechanism codes males' genotypes as homozygous females, whereas under XCI-E, males are treated as heterozygous females. By comprehensive simulations, we evaluate tests of the hypothesis under a computationally efficient score statistic. In summary, the FMM renders reduced bias and commensurate power compared to XCI, XCI-E, and alternative strategies while maintaining adequate Type 1 error control. The proposed method has far-reaching applications. In particular, we illustrate its usage on a large-scale human microbiome study, the Genetic, Environmental and Microbial (GEM) project, to test for the genetic association on the X chromosome.

RevDate: 2019-01-16

Britton GJ, Contijoch EJ, Mogno I, et al (2019)

Microbiotas from Humans with Inflammatory Bowel Disease Alter the Balance of Gut Th17 and RORγt+ Regulatory T Cells and Exacerbate Colitis in Mice.

Immunity, 50(1):212-224.e4.

Microbiota are thought to influence the development and progression of inflammatory bowel disease (IBD), but determining generalizable effects of microbiota on IBD etiology requires larger-scale functional analyses. We colonized germ-free mice with intestinal microbiotas from 30 healthy and IBD donors and determined the homeostatic intestinal T cell response to each microbiota. Compared to microbiotas from healthy donors, transfer of IBD microbiotas into germ-free mice increased numbers of intestinal Th17 cells and Th2 cells and decreased numbers of RORγt+ Treg cells. Colonization with IBD microbiotas exacerbated disease in a model where colitis is induced upon transfer of naive T cells into Rag1-/- mice. The proportions of Th17 and RORγt+ Treg cells induced by each microbiota were predictive of human disease status and accounted for disease severity in the Rag1-/- colitis model. Thus, an impact on intestinal Th17 and RORγt+ Treg cell compartments emerges as a unifying feature of IBD microbiotas, suggesting a general mechanism for microbial contribution to IBD pathogenesis.

RevDate: 2019-01-16

Griffith JC, XC Morgan (2019)

Invited Commentary: Improving accessibility of the Human Microbiome Project data through integration with R/Bioconductor.

American journal of epidemiology pii:5288095 [Epub ahead of print].

Alterations in the composition of the microbiota have been implicated in many diseases. The Human Microbiome Project (HMP) provides a comprehensive reference dataset of the "normal" human microbiome of 242 healthy adults at five major body sites. The HMP used both 16S ribosomal RNA gene sequencing and whole-genome metagenomic sequencing to profile the subjects' microbial communities. However, accessing and analyzing the HMP dataset still presents technical and bioinformatic challenges, as researchers must import the microbiome data, integrate phylogenetic trees, and access and merge public and restricted metadata. In this issue, the HMP16SData R/Bioconductor package developed by Schiffer and colleagues (Am J Epidemiol. XXX; XX (XX): XX-XXX) greatly simplifies access to the HMP data by combining 16S taxonomic abundance data, public patient metadata, and phylogenetic trees as a single data object. The authors also provide an interface for users with approved dbGaP projects to easily retrieve and merge the controlled-access HMP metadata. This package has a broad range of appeal to researchers across disciplines and with various levels of expertise in using R and/or other statistical tools. This will translate to improved data accessibility for public health research, with data from healthy individuals serving as a reference for disease-associated studies.

RevDate: 2019-01-16

Schiffer L, Azhar R, Shepherd L, et al (2019)

HMP16SData: Efficient Access to the Human Microbiome Project through Bioconductor.

American journal of epidemiology pii:5288094 [Epub ahead of print].

Phase 1 of the Human Microbiome Project (HMP) investigated 18 body subsites of 239 healthy American adults, to produce the first comprehensive reference for the composition and variation of the "healthy" human microbiome. Publicly-available data sets from amplicon sequencing of two 16S ribosomal RNA variable regions, with extensive controlled-access participant data, provide a reference for ongoing microbiome studies. However, utilization of these data sets can be hindered by the complex bioinformatic steps required to access, import, decrypt, and merge the various components in formats suitable for ecological and statistical analysis. The HMP16SData package provides count data for both 16S ribosomal RNA variable regions, integrated with phylogeny, taxonomy, public participant data, and controlled participant data for authorized researchers, using standard integrative Bioconductor data objects. By removing bioinformatic hurdles of data access and management, HMP16SData enables epidemiologists with only basic R skills to quickly analyze HMP data.

RevDate: 2019-01-16

Sessa L, Reddel S, Manno E, et al (2019)

Distinct gut microbiota profile in ART-treated perinatally HIV-infected patients associated with cardiac and inflammatory biomarkers.

AIDS (London, England) [Epub ahead of print].

OBJECTIVE: Persistent inflammation and higher risk to develop cardiovascular diseases (CVDs) still represent a major complication for HIV-infected patients despite effective antiretroviral therapy (ART). We investigated the correlation between the gut microbiota (GM) profile, markers of inflammation, vascular endothelial activation (VEA) and microbial translocation (MT) in perinatally HIV-infected patients (PHIV) under ART.

DESIGN: Cross-sectional study including sixty-one ART-treated PHIV (age range 3-30 years old) and seventy-one age-matched healthy controls (CTRL). Blood and stool sample were collected at the same time and analyzed for GM composition and plasma biomarkers.

METHODS: GM composition was determined by 16S rRNA targeted-metagenomics. Soluble markers of MT, SI and VEA were quantified by ELISA or Luminex assay. Markers of immune activation were analyzed by flow cytometry on CD4+ and CD8+T-cells.

RESULTS: We identified two distinct GM profiles (group A and B) among PHIV. No different clinical parameters (age, sex, ethnicity, clinical class), dietary and sexual habits were found between the groups. The group A showed a relative dominance of Akkermansia muciniphila (A.muciniphila), whereas GM of group B was characterized by a higher biodiversity. The analysis of soluble markers revealed a significantly higher level of sE-selectin (p = 0.0296), ICAM-1 (p = 0.0028), VCAM-1 (p = 0.0230), IL-6 (p = 0.0247) and sCD14 (p = 0.0142) in group A compared to group B.

CONCLUSIONS: Distinctive GM profiles are differently associated with inflammation, MT and VEA. Future studies are needed in order to understand the role of A.muciniphila and risk to develop CVDs in PHIV.

RevDate: 2019-01-15

Gutiérrez-Barranquero JA, Parages ML, Dobson ADW, et al (2019)

Genome Sequence of Paracoccus sp. JM45, a Bacterial Strain Isolated from a Marine Sponge with a Dual Quorum Sensing Inhibition Activity.

Microbiology resource announcements, 8(2): pii:MRA01496-18.

The draft genome sequence of Paracoccus sp. strain JM45, isolated from a marine sponge harvested off the west coast of Ireland, is reported here. Quorum sensing and quorum sensing inhibition activities have been reported recently for this bacterium, and genomic analysis supports its potential use for novel therapeutic development.

RevDate: 2019-01-12

Feng S, SL McLellan (2019)

Highly specific sewage-derived Bacteroides qPCR assays target sewage polluted waters.

Applied and environmental microbiology pii:AEM.02696-18 [Epub ahead of print].

The identification of sewage contamination in water has primarily relied on detection of the human Bacteroides using markers within the V2 region of the 16S ribosomal RNA (rRNA) gene. Despite establishment of multiple assays that target the HF183 cluster (i.e., Bacteroides dorei) and other Bacteroides organisms (e.g., Bacteroides thetaiotomicron), the potential for more human-associated markers in this genus has not been explored in depth. We examined Bacteroides population structure in sewage and animal hosts across the V4V5 and V6 hypervariable regions. Using near full-length cloned sequences, we identified the sequences in the V4V5 and V6 hypervariable regions that are linked to the HF183 marker in V2 region and found these sequences were present in multiple animals. In addition, the V4V5 and V6 regions contained human fecal marker sequences for organisms that were independent of HF183 cluster. The most abundant Bacteroides in untreated sewage was not human associated but pipe derived. Two TaqMan qPCR assays were developed targeting the V4V5 and V6 regions of this organism. Validation studies using fecal samples from seven animal hosts (n=76) and uncontaminated water samples (n=30) demonstrated their high specificity for sewage. Freshwater Bacteroides were also identified in uncontaminated water samples, demonstrating that measures of total Bacteroides do not reflect fecal pollution. Comparison of two previously described human Bacteroides assays (HB and HF183/BacR287) in municipal wastewater influent and sewage contaminated urban water samples produced identical results, illustrating they target the same organism. Detection of sewage-derived Bacteroides provided an independent measure of sewage-impacted waters.IMPORTANCEBacteroides are major member of the gut microbiota and host-specific organisms within this genus have been used extensively to gain information on pollution sources. This study provides a broad view of the population structure of Bacteroides within sewage to contextualize the well-studied HF183 marker for a human-associated Bacteroides The study also delineates host-specific sequence patterns across multiple hypervariable regions of the 16S rRNA gene to improve our ability to use sequence data to assess water quality. Here, we demonstrate that regions downstream of the HF183 marker are non-specific, but other potential human-associated markers are present. Further, we show the most abundant Bacteroides in sewage is free-living, rather than host associated, and specifically found in sewage. Quantitative PCR assays that target organism specific to sewer pipes offer measures that are independent of the human microbiome for identifying sewage pollution in water.

RevDate: 2019-01-10

Rowan-Nash AD, Korry BJ, Mylonakis E, et al (2019)

Cross-Domain and Viral Interactions in the Microbiome.

Microbiology and molecular biology reviews : MMBR, 83(1): pii:83/1/e00044-18.

SUMMARYThe importance of the microbiome to human health is increasingly recognized and has become a major focus of recent research. However, much of the work has focused on a few aspects, particularly the bacterial component of the microbiome, most frequently in the gastrointestinal tract. Yet humans and other animals can be colonized by a wide array of organisms spanning all domains of life, including bacteria and archaea, unicellular eukaryotes such as fungi, multicellular eukaryotes such as helminths, and viruses. As they share the same host niches, they can compete with, synergize with, and antagonize each other, with potential impacts on their host. Here, we discuss these major groups making up the human microbiome, with a focus on how they interact with each other and their multicellular host.

RevDate: 2019-01-08

Satitsuksanoa P, Jansen K, Głobińska A, et al (2018)

Regulatory Immune Mechanisms in Tolerance to Food Allergy.

Frontiers in immunology, 9:2939.

Oral tolerance can develop after frequent exposure to food allergens. Upon ingestion, food is digested into small protein fragments in the gastrointestinal tract. Small food particles are later absorbed into the human body. Interestingly, some of these ingested food proteins can cause allergic immune responses, which can lead to food allergy. So far it has not been completely elucidated how these proteins become immunogenic and cause food allergies. In contrast, oral tolerance helps to prevent the pathologic reactions against different types of food antigens from animal or plant origin. Tolerance to food is mainly acquired by dendritic cells, epithelial cells in the gut, and the gut microbiome. A subset of CD103+ DCs is capable of inducing T regulatory cells (Treg cells) that express anti-inflammatory cytokines. Anergic T cells also contribute to oral tolerance, by reducing the number of effector cells. Similar to Treg cells, B regulatory cells (Breg cells) suppress effector T cells and contribute to the immune tolerance to food allergens. Furthermore, the human microbiome is an essential mediator in the induction of oral tolerance or food allergy. In this review, we outline the current understanding of regulatory immune mechanisms in oral tolerance. The biological changes reflecting early consequences of immune stimulation with food allergens should provide useful information for the development of novel therapeutic treatments.

RevDate: 2019-01-08

Xiao J, Chen L, Yu Y, et al (2018)

A Phylogeny-Regularized Sparse Regression Model for Predictive Modeling of Microbial Community Data.

Frontiers in microbiology, 9:3112.

Fueled by technological advancement, there has been a surge of human microbiome studies surveying the microbial communities associated with the human body and their links with health and disease. As a complement to the human genome, the human microbiome holds great potential for precision medicine. Efficient predictive models based on microbiome data could be potentially used in various clinical applications such as disease diagnosis, patient stratification and drug response prediction. One important characteristic of the microbial community data is the phylogenetic tree that relates all the microbial taxa based on their evolutionary history. The phylogenetic tree is an informative prior for more efficient prediction since the microbial community changes are usually not randomly distributed on the tree but tend to occur in clades at varying phylogenetic depths (clustered signal). Although community-wide changes are possible for some conditions, it is also likely that the community changes are only associated with a small subset of "marker" taxa (sparse signal). Unfortunately, predictive models of microbial community data taking into account both the sparsity and the tree structure remain under-developed. In this paper, we propose a predictive framework to exploit sparse and clustered microbiome signals using a phylogeny-regularized sparse regression model. Our approach is motivated by evolutionary theory, where a natural correlation structure among microbial taxa exists according to the phylogenetic relationship. A novel phylogeny-based smoothness penalty is proposed to smooth the coefficients of the microbial taxa with respect to the phylogenetic tree. Using simulated and real datasets, we show that our method achieves better prediction performance than competing sparse regression methods for sparse and clustered microbiome signals.

RevDate: 2019-01-03

Osman AEG, JJ Luke (2019)

The Impact of the Fecal Microbiome on Cancer Immunotherapy.

BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy pii:10.1007/s40259-018-0328-8 [Epub ahead of print].

Recent advances in culture-free methods of studying the human microbiome, coupled with strong bioinformatics tools, have provided new insights on the role of the human microbiome in health and disease. The human gut, in particular, houses a vast number and diverse variety of microbes. A plethora of evidence has demonstrated the significant effects of the gut microbiome on local and systemic immunity. Studies in hematopoietic stem cell transplantation recipients provided early evidence of the involvement of the gut microbiome in the development of graft-versus-host disease and its related mortality. Cancer immunotherapy and checkpoint inhibitors, in particular, harness the power of the host's immune system to fight a range of malignancies. Resistance to immunotherapy and fatal immune-related adverse events both continue to be challenges in the field. The role of the human gut microbiome in affecting the response to immunotherapy was recently uncovered through a series of preclinical and clinical studies. The evidence presented in these studies provides tremendous potential for gut microbes to be used for biomarker development and therapeutic intervention trials.

RevDate: 2018-12-28

van Dijkhuizen EHP, Del Chierico F, Malattia C, et al (2018)

Microbiome analytics of the gut microbiota in juvenile idiopathic arthritis patients: an observational, longitudinal cohort study.

Arthritis & rheumatology (Hoboken, N.J.) [Epub ahead of print].

OBJECTIVES: To assess the composition of gut microbiota in Italian and Dutch juvenile idiopathic arthritis (JIA) patients at baseline, in inactive disease and persistent activity, compared to healthy controls.

METHODS: In a prospective, multicenter, observational cohort study, fecal samples were collected of 78 Italian and 21 Dutch treatment-naïve JIA patients at baseline with less than 6 months disease duration and compared to 107 geography-matched samples of healthy children. Furthermore, 44 follow up samples in inactive disease and 25 in persistent activity were analyzed. Gut microbiota composition was determined by 16S rRNA-based-metagenomics. The α- and β-diversity were computed, and log-ratios of relative abundance were compared between patients and healthy controls using random forest models and logistic regression.

RESULTS: Italian baseline samples showed reduced richness compared to healthy controls (p <0.001). Random forest distinguished Italian baseline samples from controls and suggested differences between Dutch samples and controls (area under the curve >0.99 and 0.71, respectively). Mainly the Operational Taxonomic Units (OTUs) Erysipelotrichaceae (increased in patients), Allobaculum (decreased) and Faecalibacterium prausnitzii (increased) showed different relative abundance in Italian baseline samples compared to controls after controlling for multiple comparisons. Some OTUs differed between Dutch samples and healthy controls, but no evidence remained after controlling for multiple comparisons. No differences were found in paired analysis between Italian baseline and inactive disease samples.

CONCLUSIONS: We found evidence for dysbiosis in JIA patients. Only patient/control status, age and geographical origin appeared to be drivers of the microbiota profiles, regardless of disease activity stage, inflammation and autoimmunity markers. This article is protected by copyright. All rights reserved.

RevDate: 2018-12-27

Wei F, Wu Q, Hu Y, et al (2018)

Conservation metagenomics: a new branch of conservation biology.

Science China. Life sciences pii:10.1007/s11427-018-9423-3 [Epub ahead of print].

Multifaceted approaches are required to monitor wildlife populations and improve conservation efforts. In the last decade, increasing evidence suggests that metagenomic analysis offers valuable perspectives and tools for identifying microbial communities and functions. It has become clear that gut microbiome plays a critical role in health, nutrition, and physiology of wildlife, including numerous endangered animals in the wild and in captivity. In this review, we first introduce the human microbiome and metagenomics, highlighting the importance of microbiome for host fitness. Then, for the first time, we propose the concept of conservation metagenomics, an emerging subdiscipline of conservation biology, which aims to understand the roles of the microbiota in evolution and conservation of endangered animals. We define what conservation metagenomics is along with current approaches, main scientific issues and significant implications in the study of host evolution, physiology, nutrition, ecology and conservation. We also discuss future research directions of conservation metagenomics. Although there is still a long way to go, conservation metagenomics has already shown a significant potential for improving the conservation and management of wildlife.

RevDate: 2018-12-25

Zhang J, Zhang F, Zhao C, et al (2018)

Dysbiosis of the gut microbiome is associated with thyroid cancer and thyroid nodules and correlated with clinical index of thyroid function.

Endocrine pii:10.1007/s12020-018-1831-x [Epub ahead of print].

PURPOSE: Thyroid cancer and thyroid nodules are the most prevalent form of thyroid endocrine disorder. The balance of gut microbiome is highly crucial for a healthy human body, especially for the immune and endocrine system. However, the relationship between gut microbiome and the thyroid endocrine disorders such as thyroid cancer and thyroid nodules has not been reported yet.

METHODS: A cohort of 74 patients was recruited for this study. Among them, 20 patients had thyroid cancer, 18 patients had thyroid nodules, and 36 were matched healthy controls. Gut microbiome composition was analyzed by 16S rRNA (16S ribosomal RNA) gene-based sequencing protocol.

RESULTS: We compared the gut microbiome results of 74 subjects and established the correlation between gut microbiome and thyroid endocrine function for both thyroid cancer and thyroid nodules. The results inferred that alpha and beta diversity were different for patients with thyroid tumor than the healthy controls (p < 0.01). In comparison to healthy controls, the relative abundance of Neisseria (p < 0.001) and Streptococcus (p < 0.001) was significantly higher for thyroid cancer and thyroid nodules. Butyricimonas (p < 0.001) and Lactobacillus (p < 0.001) displayed notably lower relative abundance for thyroid cancer and thyroid nodules, respectively. It was also found that the clinical indexes were correlated with gut microbiome.

CONCLUSION: Our results indicate that both thyroid cancer and thyroid nodules are associated with the composition of gut microbiome. These results may support further clinical diagnosis to a great extent and help in developing potential probiotics to facilitate the treatment of thyroid cancer and thyroid nodules.

RevDate: 2018-12-22

Nobili V, Mosca A, Alterio T, et al (2018)

Fighting Fatty Liver Diseases with Nutritional Interventions, Probiotics, Symbiotics, and Fecal Microbiota Transplantation (FMT).

Advances in experimental medicine and biology [Epub ahead of print].

Pediatric obesity is rising worldwide leading the worrying phenomenon of nonalcoholic fatty liver disease (NAFLD) to shift into one of the most frequent causes of chronic liver illness in childhood. Occurrence of NAFLD depends on several factors such as the geographical area and the diagnostic modalities used; overall it ranges between 3% and 10% of pediatric population, increasing up to 70% in patients with metabolic comorbidities (Manco M, Bottazzo G, DeVito R et al, J Am Coll Nutr 27:667-676, 2008).Recent findings have related the intestinal microbiota to a plethora of pathological conditions, including type 2 diabetes (T2D), obesity, and nonalcoholic steatohepatitis (NASH). One of the emerging areas of the study is the link between liver diseases and gut microbiome, which has added new information to the understanding of the so-called gut-liver axis.In order to address the role of gut microbiome in NAFLD onset and progression, it is necessary to "decipher" operational codes for microbiome investigation within the context of advanced laboratory medicine to capture microbiome features and, hence, to address the function of the intestinal microbiome within the gut microbiota-liver axis.Results of these investigations have allowed the beginning of implementing the usage of probiotics and symbiotics in the medical approach of obesity and NAFLD in adults and children. Several randomized clinical trials (RCTs) have been already published on fecal microbiota transplantation (FMT), T2D, NASH, and inflammatory bowel disease (IBD).This review proposes to describe the current state of knowledge on the ways fatty liver diseases can be addressed with nutritional interventions, probiotics, symbiotics, and FMT.

RevDate: 2018-12-22

Stubbendieck RM, May DS, Chevrette MG, et al (2018)

Competition among nasal bacteria suggests a role for siderophore-mediated interactions in shaping the human nasal microbiota.

Applied and environmental microbiology pii:AEM.02406-18 [Epub ahead of print].

Resources available in the human nasal cavity are limited. Therefore, to successfully colonize the nasal cavity, bacteria must compete for scarce nutrients. Competition may occur directly through interference (e.g., antibiotics) or indirectly by nutrient sequestration. To investigate the nature of nasal bacterial competition, we performed co-culture inhibition assays between nasal Actinobacteria and Staphylococcus spp. We found that coagulase-negative staphylococci (CoNS) isolates were sensitive to growth inhibition by Actinobacteria but Staphylococcus aureus isolates were resistant to inhibition. Among Actinobacteria, we observed that Corynebacterium spp. were variable in their ability to inhibit CoNS. We sequenced the genomes of ten Corynebacterium spp. isolates, including three Corynebacterium propinquum that strongly inhibited CoNS and seven other Corynebacterium spp. isolates that only weakly inhibited CoNS Using a comparative genomics approach, we found that the C. propinquum genomes were enriched in genes for iron acquisition and encoded a biosynthetic gene cluster (BGC) for siderophore production, absent in the non-inhibitory Corynebacterium spp. genomes. Using a chromeazurol S assay, we confirmed that C. propinquum produced siderophores. We demonstrated that iron supplementation rescued CoNS from inhibition by C. propinquum, suggesting that inhibition was due to iron restriction through siderophore production. Through comparative metabolomics and molecular networking, we identified the siderophore produced by C. propinquum as dehydroxynocardamine. Finally, we confirmed that the dehydroxynocardamine BGC is expressed in vivo by analyzing human nasal metatranscriptomes from the NIH Human Microbiome Project. Together, our results suggest that bacteria produce siderophores to compete for limited available iron in the nasal cavity and improve their fitness.IMPORTANCE Within the nasal cavity, interference competition through antimicrobial production is prevalent. For instance, nasal Staphylococcus spp. strains can inhibit the growth of other bacteria through the production of nonribosomal peptides and ribosomally synthesized and post-translationally modified peptides. In contrast, bacteria engaging in exploitation competition modify the external environment to prevent competitors from growing, usually by depleting access to essential nutrients. As the nasal cavity is a nutrient limited environment, we hypothesized that exploitation competition occurs in this system. We determined that Corynebacterium propinquum produces an iron-chelating siderophore and this iron-sequestering molecule correlates with the ability to inhibit the growth of coagulase-negative staphylococci. Further, we found that the genes required for siderophore production are expressed in vivo Thus, though siderophore production by bacteria is often considered a virulence trait, our work indicates that bacteria may produce siderophores to compete for limited iron in the human nasal cavity.

RevDate: 2018-12-22

Yang AJ, Marito S, Yang JJ, et al (2018)

A Microtube Array Membrane (MTAM) Encapsulated Live Fermenting Staphylococcus epidermidis as a Skin Probiotic Patch against Cutibacterium acnes.

International journal of molecular sciences, 20(1): pii:ijms20010014.

Antibiotics without selectivity for acne treatment may destroy the beneficial microbes in the human microbiome that helps to fight Cutibacterium acnes (C. acnes), a bacterium associated with inflammatory acne vulgaris. Probiotic treatment by direct application of live Staphylococcus epidermidis (S. epidermidis) onto the open acne lesions may run the risk of bloodstream infections. Here, we fabricated the polysulfone microtube array membranes (PSF MTAM) to encapsulate probiotic S.epidermidis. We demonstrate that the application of the encapsulation of S.epidermidis in PSF MTAM enhanced the glycerol fermentation activities of S. epidermidis. To mimic the granulomatous type of acne inflammatory acne vulgaris, the ears of mice were injected intradermally with C.acnes to induce the secretion of macrophage inflammatory protein-2 (MIP-2), a murine counterpart of human interleukin (IL)-8. The C. acnes-injected mouse ears were covered with a PST MTAM encapsulated with or without S.epidermidis in the presence of glycerol. The application of S.epidermidis-encapsulated PST MTAM plus glycerol onto the C.acnes-injected mouse ears considerably reduced the growth of C. acnes and the production of MIP-2. Furthermore, no S. epidermidis leaked from PSF MTAM into mouse skin. The S. epidermidis-encapsulated PST MTAM functions as a probiotic acne patch.

RevDate: 2018-12-21

Coryell M, McAlpine M, Pinkham NV, et al (2018)

The gut microbiome is required for full protection against acute arsenic toxicity in mouse models.

Nature communications, 9(1):5424 pii:10.1038/s41467-018-07803-9.

Arsenic poisons an estimated 200 million people worldwide through contaminated food and drinking water. Confusingly, the gut microbiome has been suggested to both mitigate and exacerbate arsenic toxicity. Here, we show that the microbiome protects mice from arsenic-induced mortality. Both antibiotic-treated and germ-free mice excrete less arsenic in stool and accumulate more arsenic in organs compared to control mice. Mice lacking the primary arsenic detoxification enzyme (As3mt) are hypersensitive to arsenic after antibiotic treatment or when derived germ-free, compared to wild-type and/or conventional counterparts. Human microbiome (stool) transplants protect germ-free As3mt-KO mice from arsenic-induced mortality, but protection depends on microbiome stability and the presence of specific bacteria, including Faecalibacterium. Our results demonstrate that both a functional As3mt and specific microbiome members are required for protection against acute arsenic toxicity in mouse models. We anticipate that the gut microbiome will become an important explanatory factor of disease (arsenicosis) penetrance in humans, and a novel target for prevention and treatment strategies.

RevDate: 2018-12-21

Altomare A, Putignani L, Del Chierico F, et al (2018)

Gut mucosal-associated microbiota better discloses Inflammatory Bowel Disease differential patterns than faecal microbiota.

Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver pii:S1590-8658(18)31260-X [Epub ahead of print].

BACKGROUND: Growing evidence supports the potential role of intestinal microbiota in the pathophysiology of Inflammatory Bowel Diseases (IBD) even if the literature does not reveal uniform alterations. The aim of the study was to evaluate the mucosal (MM) and faecal microbiota (FM) composition in a cohort of IBD patients compared to healthy controls (CTRLs).

METHODS: Faecal and mucosal samples were collected from 14 IBD patients and 11 CTRLs. The V1-V3 region of 16S rRNA locus was amplified on a 454-Junior Genome Sequencer. Reads were grouped into operational taxonomic units (OTUs) at a sequence similarity level of 97% for taxonomic assignment, and aligned for OTUs matching against Greengenes database.

RESULTS: Irrespective of disease localization and activity, in the MM of IBD patients a statistically significant increase of Proteobacteria (especially Enterobacteriaceae, Acidaminococcus, Veillonella dispar) and decrease of Firmicutes (especially Roseburia and Faecalibacterium prausnitzii) and Actinobacteria was found compared to CTRLs. In the colon district some specific bacterial biomarkers were identified: Enterobacteriaceae for IBD stools, Bacteroides for IBD biopsies, Mogibacteriaceae, Ruminococcaceae and Prevotella for CTRL stools, Ruminococcaceae for CTRL biopsies.

CONCLUSIONS: The profiles of FM were more similar to CTRLs, suggesting that microbiota adhering to the gut mucosa better discriminates patients from controls, with the identification of some interesting biomarkers.

RevDate: 2018-12-21

Sánchez-Ponce Y, Varela-Fascinetto G, Romo-Vázquez JC, et al (2018)

Simultaneous Detection of Beta and Gamma Human Herpesviruses by Multiplex qPCR Reveals Simple Infection and Coinfection Episodes Increasing Risk for Graft Rejection in Solid Organ Transplantation.

Viruses, 10(12): pii:v10120730.

Herpesviruses are common components of the human microbiome that become clinically relevant when a competent immunosurveillance is compromised, such as in transplantation. Members of the beta and gamma subfamilies are associated with a wide diversity of pathologies, including end-organ disease and cancer. In this study, we developed a multiplex qPCR technique with high specificity, sensitivity, efficiency and predictability that allowed the simultaneous detection and quantification of beta and gamma human herpesviruses. The technique was tested in a cohort of 34 kidney- or liver-transplanted pediatric patients followed up for up to 12 months post-transplant. Viral load was determined in 495 leukocyte-plasma paired samples collected bi-weekly or monthly. Human herpesvirus (HHV) 7 was the herpesvirus most frequently found in positive samples (39%), followed by Epstein-Barr virus (EBV) (20%). Also, EBV and HHV7 were present in the majority of coinfection episodes (62%). The share of positive samples exclusively detected either in leukocytes or plasma was 85%, suggesting that these herpesviruses tended to take a latent or lytic path in an exclusive manner. Infection by human cytomegalovirus (HCMV) and HHV6, as well as coinfection by EBV/HHV7 and EBV/HHV6/HHV7, were associated with graft rejection (RR = 40.33 (p = 0.0013), 5.60 (p = 0.03), 5.60 (p = 0.03) and 17.64 (p = 0.0003), respectively). The routine monitoring of beta and gamma herpesviruses should be mandatory in transplant centers to implement preventive strategies.

RevDate: 2018-12-19

Proal A, T Marshall (2018)

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome in the Era of the Human Microbiome: Persistent Pathogens Drive Chronic Symptoms by Interfering With Host Metabolism, Gene Expression, and Immunity.

Frontiers in pediatrics, 6:373.

The illness ME/CFS has been repeatedly tied to infectious agents such as Epstein Barr Virus. Expanding research on the human microbiome now allows ME/CFS-associated pathogens to be studied as interacting members of human microbiome communities. Humans harbor these vast ecosystems of bacteria, viruses and fungi in nearly all tissue and blood. Most well-studied inflammatory conditions are tied to dysbiosis or imbalance of the human microbiome. While gut microbiome dysbiosis has been identified in ME/CFS, microbes and viruses outside the gut can also contribute to the illness. Pathobionts, and their associated proteins/metabolites, often control human metabolism and gene expression in a manner that pushes the body toward a state of illness. Intracellular pathogens, including many associated with ME/CFS, drive microbiome dysbiosis by directly interfering with human transcription, translation, and DNA repair processes. Molecular mimicry between host and pathogen proteins/metabolites further complicates this interference. Other human pathogens disable mitochondria or dysregulate host nervous system signaling. Antibodies and/or clonal T cells identified in patients with ME/CFS are likely activated in response to these persistent microbiome pathogens. Different human pathogens have evolved similar survival mechanisms to disable the host immune response and host metabolic pathways. The metabolic dysfunction driven by these organisms can result in similar clusters of inflammatory symptoms. ME/CFS may be driven by this pathogen-induced dysfunction, with the nature of dysbiosis and symptom presentation varying based on a patient's unique infectious and environmental history. Under such conditions, patients would benefit from treatments that support the human immune system in an effort to reverse the infectious disease process.

RevDate: 2018-12-18

Tedijanto C, Olesen SW, Grad YH, et al (2018)

Estimating the proportion of bystander selection for antibiotic resistance among potentially pathogenic bacterial flora.

Proceedings of the National Academy of Sciences of the United States of America pii:1810840115 [Epub ahead of print].

Bystander selection-the selective pressure for resistance exerted by antibiotics on microbes that are not the target pathogen of treatment-is critical to understanding the total impact of broad-spectrum antibiotic use on pathogenic bacterial species that are often carried asymptomatically. However, to our knowledge, this effect has never been quantified. We quantify bystander selection for resistance for a range of clinically relevant antibiotic-species pairs as the proportion of all antibiotic exposures received by a species for conditions in which that species was not the causative pathogen ("proportion of bystander exposures"). Data sources include the 2010-2011 National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey, the Human Microbiome Project, and additional carriage and etiological data from existing literature. For outpatient prescribing in the United States, we find that this proportion over all included antibiotic classes is over 80% for eight of nine organisms of interest. Low proportions of bystander exposure are often associated with infrequent bacterial carriage or concentrated prescribing of a particular antibiotic for conditions caused by the species of interest. Applying our results, we roughly estimate that pneumococcal conjugate vaccination programs result in nearly the same proportional reduction in total antibiotic exposures of Streptococcus pneumoniae, Staphylococcus aureus, and Escherichia coli, despite the latter two organisms not being targeted by the vaccine. These results underscore the importance of considering antibiotic exposures of bystanders, in addition to the target pathogen, in measuring the impact of antibiotic resistance interventions.

RevDate: 2018-12-18

Relman DA, M Lipsitch (2018)

Microbiome as a tool and a target in the effort to address antimicrobial resistance.

Proceedings of the National Academy of Sciences of the United States of America pii:1717163115 [Epub ahead of print].

Reciprocal, intimate relationships between the human microbiome and the host immune system are shaped by past microbial encounters and prepare the host for future ones. Antibiotics and other antimicrobials leave their mark on both the microbiome and host immunity. Antimicrobials alter the structure of the microbiota, expand the host-specific pool of antimicrobial-resistance genes and organisms, degrade the protective effects of the microbiota against invasion by pathogens, and may impair vaccine efficacy. Through these effects on the microbiome they may affect immune responses. Vaccines that exert protective or therapeutic effects against pathogens may reduce the use of antimicrobials, the development and spread of antimicrobial resistance, and the harmful impacts of these drugs on the microbiome. Other strategies involving manipulation of the microbiome to deplete antibiotic-resistant organisms or to enhance immune responses to vaccines may prove valuable in addressing antimicrobial resistance as well. This article describes the intersections of immunity, microbiome and antimicrobial exposure, and the use of vaccines and other alternative strategies for the control and management of antimicrobial resistance.

RevDate: 2018-12-15

Romani L, Pane S, Severini C, et al (2018)

Challenging diagnosis of congenital malaria in non-endemic areas.

Malaria journal, 17(1):470 pii:10.1186/s12936-018-2614-9.

BACKGROUND: Congenital malaria is usually defined as the detection of asexual forms of Plasmodium spp. in a blood sample of a neonate during perinatal age if there is no possibility of postpartum infection by a mosquito bite. The incidence of congenital malaria is highly variable and seems related to several factors, such as different diagnostic methods for Plasmodium spp. detection, and area in which the epidemiologic analyses are performed. In non-endemic countries, cases of congenital malaria are rare. Hereby, a case of a congenital malaria in an HIV exposed child is reported.

CASE PRESENTATION: A 2-month-old male child was admitted to Bambino Gesù Children's Hospital due to anaemia and exposure to HIV. He was born prematurely in Italy by cesarean section at 34 weeks' gestation after a bicorial, biamniotic pregnancy by a migrant woman from Nigeria. He was the first of non-identical twins. Combined with anaemia, spleen and liver enlargement was noted, malaria was hypothesized. Malaria laboratory panel was performed on the newborn, mother and other twin blood samples, as follows: (i) malaria rapid diagnostic test (RDT); (ii) Giemsa-stained thick and thin blood smears for Plasmodium spp. identification and parasitaemia titration; (iii) molecular screening and typing of Plasmodium spp. by multiplex qualitative PCR assay based on 18S rRNA gene. Genotyping of Plasmodium falciparum isolates from mother and child was performed by neutral microsatellite and highly polymorphic marker amplification.

CONCLUSIONS: The maternal RDT sample was negative, while the infant RDT was positive; in both cases microscopy of blood smears and PCR showed infection with P. falciparum. Two of the genotypic molecular markers displayed different allelic variants between the two samples. This difference could imply infection multiplicity of the mother during the pregnancy, possibly harbouring more than one isolate, only one of them being transmitted to the newborn while the other persisting in the mother's blood. Because of the increasing number of pregnant women coming from endemic areas for malaria, an accurate anamnesis of infant's mother, and the inclusion of Plasmodium spp. research into TORCH screenings for mother-infant pair at birth, aiming at reducing morbidity and mortality associated to the disease might be suitable.

RevDate: 2018-12-14

D'Argenio V (2018)

The Prenatal Microbiome: A New Player for Human Health.

High-throughput, 7(4): pii:ht7040038.

The last few years have featured an increasing interest in the study of the human microbiome and its correlations with health status. Indeed, technological advances have allowed the study of microbial communities to reach a previously unthinkable sensitivity, showing the presence of microbes also in environments usually considered as sterile. In this scenario, microbial communities have been described in the amniotic fluid, the umbilical blood cord, and the placenta, denying a dogma of reproductive medicine that considers the uterus like a sterile womb. This prenatal microbiome may play a role not only in fetal development but also in the predisposition to diseases that may develop later in life, and also in adulthood. Thus, the aim of this review is to report the current knowledge regarding the prenatal microbiome composition, its association with pathological processes, and the future perspectives regarding its manipulation for healthy status promotion and maintenance.

RevDate: 2018-12-07

Yang J, Mu X, Wang Y, et al (2018)

Dysbiosis of the Salivary Microbiome Is Associated With Non-smoking Female Lung Cancer and Correlated With Immunocytochemistry Markers.

Frontiers in oncology, 8:520.

Background: Association between oral bacteria and increased risk of lung cancer have been reported in several previous studies, however, the potential association between salivary microbiome and lung cancer in non-smoking women have not been evaluated. There is also no report on the relationship between immunocytochemistry markers and salivary microbiota. Method: In this study, we assessed the salivary microbiome of 75 non-smoking female lung cancer patients and 172 matched healthy individuals using 16S rRNA gene amplicon sequencing. We also calculated the Spearman's rank correlation coefficient between salivary microbiota and three immunohistochemical markers (TTF-1, Napsin A and CK7). Result: We analyzed the salivary microbiota of 247 subjects and found that non-smoking female lung cancer patients exhibited oral microbial dysbiosis. There was significantly lower microbial diversity and richness in lung cancer patients when compared to the control group (Shannon index, P < 0.01; Ace index, P < 0.0001). Based on the analysis of similarities, the composition of the microbiota in lung cancer patients also differed from that of the control group (r = 0.454, P < 0.001, unweighted UniFrac; r = 0.113, P < 0.01, weighted UniFrac). The bacterial genera Sphingomonas (P < 0.05) and Blastomonas (P < 0.0001) were relatively higher in non-smoking female lung cancer patients, whereas Acinetobacter (P < 0.001) and Streptococcus (P < 0.01) were higher in controls. Based on Spearman's correlation analysis, a significantly positive correlation can be observed between CK7 and Enterobacteriaceae (r = 0.223, P < 0.05). At the same time, Napsin A was positively associated with genera Blastomonas (r = 0.251, P < 0.05). TTF-1 exhibited a significantly positive correlation with Enterobacteriaceae (r = 0.262, P < 0.05). Functional analysis from inferred metagenomes indicated that oral microbiome in non-smoking female lung cancer patients were related to cancer pathways, p53 signaling pathway, apoptosis and tuberculosis. Conclusions: The study identified distinct salivary microbiome profiles in non-smoking female lung cancer patients, revealed potential correlations between salivary microbiome and immunocytochemistry markers used in clinical diagnostics, and provided proof that salivary microbiota can be an informative source for discovering non-invasive lung cancer biomarkers.

RevDate: 2018-12-11

Escapa IF, Chen T, Huang Y, et al (2018)

New Insights into Human Nostril Microbiome from the Expanded Human Oral Microbiome Database (eHOMD): a Resource for the Microbiome of the Human Aerodigestive Tract.

mSystems, 3(6): pii:mSystems00187-18.

The expanded Human Oral Microbiome Database (eHOMD) is a comprehensive microbiome database for sites along the human aerodigestive tract that revealed new insights into the nostril microbiome. The eHOMD provides well-curated 16S rRNA gene reference sequences linked to available genomes and enables assignment of species-level taxonomy to most next-generation sequences derived from diverse aerodigestive tract sites, including the nasal passages, sinuses, throat, esophagus, and mouth. Using minimum entropy decomposition coupled with the RDP Classifier and our eHOMD V1-V3 training set, we reanalyzed 16S rRNA V1-V3 sequences from the nostrils of 210 Human Microbiome Project participants at the species level, revealing four key insights. First, we discovered that Lawsonella clevelandensis, a recently named bacterium, and Neisseriaceae [G-1] HMT-174, a previously unrecognized bacterium, are common in adult nostrils. Second, just 19 species accounted for 90% of the total sequences from all participants. Third, 1 of these 19 species belonged to a currently uncultivated genus. Fourth, for 94% of the participants, 2 to 10 species constituted 90% of their sequences, indicating that the nostril microbiome may be represented by limited consortia. These insights highlight the strengths of the nostril microbiome as a model system for studying interspecies interactions and microbiome function. Also, in this cohort, three common nasal species (Dolosigranulum pigrum and two Corynebacterium species) showed positive differential abundance when the pathobiont Staphylococcus aureus was absent, generating hypotheses regarding colonization resistance. By facilitating species-level taxonomic assignment to microbes from the human aerodigestive tract, the eHOMD is a vital resource enhancing clinical relevance of microbiome studies. IMPORTANCE The eHOMD ( is a valuable resource for researchers, from basic to clinical, who study the microbiomes and the individual microbes in body sites in the human aerodigestive tract, which includes the nasal passages, sinuses, throat, esophagus, and mouth, and the lower respiratory tract, in health and disease. The eHOMD is an actively curated, web-based, open-access resource. eHOMD provides the following: (i) species-level taxonomy based on grouping 16S rRNA gene sequences at 98.5% identity, (ii) a systematic naming scheme for unnamed and/or uncultivated microbial taxa, (iii) reference genomes to facilitate metagenomic, metatranscriptomic, and proteomic studies and (iv) convenient cross-links to other databases (e.g., PubMed and Entrez). By facilitating the assignment of species names to sequences, the eHOMD is a vital resource for enhancing the clinical relevance of 16S rRNA gene-based microbiome studies, as well as metagenomic studies.

RevDate: 2018-12-11

Lim MY, Cho Y, M Rho (2018)

Diverse Distribution of Resistomes in the Human and Environmental Microbiomes.

Current genomics, 19(8):701-711.

The routine therapeutic use of antibiotics has caused resistance genes to be disseminated across microbial populations. In particular, bacterial strains having antibiotic resistance genes are frequently observed in the human microbiome. Moreover, multidrug-resistant pathogens are now widely spread, threatening public health. Such genes are transferred and spread among bacteria even in different environments. Advances in high throughput sequencing technology and computational algorithms have accelerated investigation into antibiotic resistance genes of bacteria. Such studies have revealed that the antibiotic resistance genes are located close to the mobility-associated genes, which promotes their dissemination. An increasing level of information on genomic sequences of resistome should expedite research on drug-resistance in our body and environment, thereby contributing to the development of public health policy. In this review, the high prevalence of antibiotic resistance genes and their exchange in the human and environmental microbiome is discussed with respect to the genomic contents. The relationships among diverse resistomes, related bacterial species, and the antibiotics are reviewed. In addition, recent advances in bioinformatics approaches to investigate such relationships are discussed.

RevDate: 2018-12-11

Ben Y, Fu C, Hu M, et al (2018)

Human health risk assessment of antibiotic resistance associated with antibiotic residues in the environment: A review.

Environmental research, 169:483-493 pii:S0013-9351(18)30429-8 [Epub ahead of print].

The extensive use of antibiotics leading to the rapid spread of antibiotic resistance poses high health risks to humans, but to date there is still lack of a quantitative model to properly assess the risks. Concerns over the health risk of antibiotic residues in the environment are mainly (1) the potential hazard of ingested antibiotic residues in the environment altering the human microbiome and promoting emergence and selection for bacteria resistance inhabiting the human body, and (2) the potential hazard of creating a selection pressure on environmental microbiome and leading to reservoirs of antibiotic resistance in the environment. We provide a holistic view of health risk assessment of antibiotic resistance associated with antibiotic residues in the environment in contrast with that of the antibiotic resistant bacteria and discuss the main knowledge gaps and the future research that should be prioritized to achieve the quantitative risk assessment. We examined and summarized the available data and information on the four core elements of antibiotic resistance associated with antibiotic residues in the environment: hazard identification, exposure assessment, dose-response assessment, and risk characterization. The data required to characterize the risks of antibiotic residues in the environment is severely limited. The main future research needs have been identified to enable better assessments of antibiotic resistance associated with antibiotic residues in the environment: (1) establishment of a standardized monitoring guide of antibiotic residues and antibiotic resistance in the environment, (2) derivation of the relationship between antibiotic levels and pathogenic antibiotic-resistance development in different settings, and (3) establishment of the dose-response relationship between pathogenic antibiotic resistant bacteria and various infection diseases. After identification of key risk determinant parameters, we propose a conceptual framework of human health risk assessments of antibiotic residues in the environment. CAPSULE: A holistic view of human health risk assessment of antibiotic residues in the environment was provided.

RevDate: 2018-12-11

Robertson RC, Manges AR, Finlay BB, et al (2018)

The Human Microbiome and Child Growth - First 1000 Days and Beyond.

Trends in microbiology pii:S0966-842X(18)30204-X [Epub ahead of print].

The assembly of microbial communities within the gastrointestinal tract during early life plays a critical role in immune, endocrine, metabolic, and other host developmental pathways. Environmental insults during this period, such as food insecurity and infections, can disrupt this optimal microbial succession, which may contribute to lifelong and intergenerational deficits in growth and development. Here, we review the human microbiome in the first 1000 days - referring to the period from conception to 2 years of age - and using a developmental model, we examine the role of early microbial succession in growth and development. We propose that an 'undernourished' microbiome is intergenerational, thereby perpetuating growth impairments into successive generations. We also identify and discuss the intertwining host-microbe-environment interactions occurring prenatally and during early infancy, which may impair the trajectories of healthy growth and development, and explore their potential as novel microbial targets for intervention.

RevDate: 2018-12-11

Blaser MJ (2018)

Our missing microbes: Short-term antibiotic courses have long-term consequences.

Cleveland Clinic journal of medicine, 85(12):928-930.

RevDate: 2018-12-06

Jeżewska-Frąckowiak J, Seroczyńska K, Banaszczyk J, et al (2018)

The promises and risks of probiotic Bacillus species.

Acta biochimica Polonica pii:2652 [Epub ahead of print].

Supplementing the human microbiome with probiotic microorganisms is a proposed solution for civilization syndromes such as dysbiosis and gastrointestinal tract (GIT) disorders. Bimodal probiotic strains of the Bacillus genus constitute the microbiota of the human environment, and are typically found in soil, water, a number of non-dairy fermented foods, as well as in human and animal GIT. Probiotic Bacillus sp. are Gram positive rods, with the ability of sporulation to survive environmental stress and preparation conditions. In vitro models of the human stomach and human studies with probiotic Bacillus reveal the mechanisms of its life cycle and sporulation. The Bacillus sp. probiotic biofilm introduces biochemical effects such as antimicrobial and enzymatic activity, thus contributing to protection from GIT and other infections. Despite the beneficial activity of Bacillus strains belonging to the safety group 1, a number of strains can pose a substantial health risk, carrying genes for various toxins or antibiotic resistance. Commercially available Bacillus probiotic preparations include strains from the subtilis and other closely related phylogenetic clades. Those intended for oral administration in humans, often encapsulated with appropriate supporting materials, still tend to be mislabeled or poorly characterized. Bacillus sp. MALDI-TOF analysis, combined with sequencing of characteristic 16S rRNA or enzyme coding genes, may provide accurate identification. A promising future application of the probiotic Bacillus sp. might be the microflora biocontrol in the human body and the closest human environment. Environmental probiotic Bacillus species display the potential to support human microflora, however controversies regarding the safety of certain strains is a key factor in their still limited application.

RevDate: 2018-12-06

Vernocchi P, Del Chierico F, Russo A, et al (2018)

Gut microbiota signatures in cystic fibrosis: Loss of host CFTR function drives the microbiota enterophenotype.

PloS one, 13(12):e0208171 pii:PONE-D-17-43072.

BACKGROUND: Cystic fibrosis (CF) is a disorder affecting the respiratory, digestive, reproductive systems and sweat glands. This lethal hereditary disease has known or suspected links to the dysbiosis gut microbiota. High-throughput meta-omics-based approaches may assist in unveiling this complex network of symbiosis modifications.

OBJECTIVES: The aim of this study was to provide a predictive and functional model of the gut microbiota enterophenotype of pediatric patients affected by CF under clinical stability.

METHODS: Thirty-one fecal samples were collected from CF patients and healthy children (HC) (age range, 1-6 years) and analysed using targeted-metagenomics and metabolomics to characterize the ecology and metabolism of CF-linked gut microbiota. The multidimensional data were low fused and processed by chemometric classification analysis.

RESULTS: The fused metagenomics and metabolomics based gut microbiota profile was characterized by a high abundance of Propionibacterium, Staphylococcus and Clostridiaceae, including Clostridium difficile, and a low abundance of Eggerthella, Eubacterium, Ruminococcus, Dorea, Faecalibacterium prausnitzii, and Lachnospiraceae, associated with overexpression of 4-aminobutyrate (GABA), choline, ethanol, propylbutyrate, and pyridine and low levels of sarcosine, 4-methylphenol, uracil, glucose, acetate, phenol, benzaldehyde, and methylacetate. The CF gut microbiota pattern revealed an enterophenotype intrinsically linked to disease, regardless of age, and with dysbiosis uninduced by reduced pancreatic function and only partially related to oral antibiotic administration or lung colonization/infection.

CONCLUSIONS: All together, the results obtained suggest that the gut microbiota enterophenotypes of CF, together with endogenous and bacterial CF biomarkers, are direct expression of functional alterations at the intestinal level. Hence, it's possible to infer that CFTR impairment causes the gut ecosystem imbalance.This new understanding of CF host-gut microbiota interactions may be helpful to rationalize novel clinical interventions to improve the affected children's nutritional status and intestinal function.

RevDate: 2018-12-06

Slobodin G, Rosner I, A Kessel (2018)

Dendritic cells in the pathogenesis of ankylosing spondylitis and axial spondyloarthritis.

Clinical rheumatology pii:10.1007/s10067-018-4388-4 [Epub ahead of print].

The interaction of dendritic cells (DCs) with the human microbiome, with distorted handling of the microbiota or its products via the direct effect of HLA B27, probably represents the initial element in the chain of events leading to the development of clinical axial spondyloarthritis. The mechanism of disease extension onto the skeleton and other tissues involved, such as uvea, may also involve migratory DCs. Finally, the role of DCs in the initiation of the inflammatory tissue response with activation of the IL-17 axis has been demonstrated. Further, some initial data suggests the possible connection of DCs with disease-related new bone formation.

RevDate: 2018-12-03

Lai PS, DC Christiani (2018)

Impact of occupational exposure on human microbiota.

Current opinion in allergy and clinical immunology [Epub ahead of print].

PURPOSE OF REVIEW: Recent evidence suggests that environmental exposures change the adult human microbiome. Here, we review recent evidence on the impact of the work microbiome and work-related chemical, metal and particulate exposures on the human microbiome.

RECENT FINDINGS: Prior literature on occupational microbial exposures has focused mainly on the respiratory effects of endotoxin, but a recent study suggests that not all endotoxin is the same; endotoxin from some species is proinflammatory, whereas endotoxin from other species is anti-inflammatory. Work with animals can change the adult human microbiome, likely through colonization. Early studies in military personnel and animal models of gulf war illness show that military exposures change the gut microbiome and increase gut permeability. Heavy metal and particulate matter exposure, which are often elevated in occupational settings, also change the gut microbiome.

SUMMARY: An emerging body of literature shows that work-related exposures can change the human microbiome. The health effects of these changes are currently not well studied. If work exposures lead to disease through alterations in the human microbiome, exposure cessation without addressing changes to the human microbiome may be ineffective for disease prevention and treatment.

RevDate: 2018-12-05

O'Toole RF, SS Gautam (2018)

The host microbiome and impact of tuberculosis chemotherapy.

Tuberculosis (Edinburgh, Scotland), 113:26-29.

The treatment of Mycobacterium tuberculosis infection is often viewed in isolation from other human microbial symbionts. Understandably, the clinical priority is eliminating active or latent tuberculosis (TB) in patients. With the increasing resolution of molecular biology technologies, it is becoming apparent that antibiotic treatment can perturb the homeostasis of the host microbiome. For example, dysbiosis of the gut microbiota has been associated with an increased risk of the development of asthma, obesity and diabetes. Therefore, fundamental questions include: Does TB chemotherapy cause disruption of the human microbiome and adverse effects in patients; and are there signature taxa of dysbiosis following TB treatment. In this review, we examine recent research on the detection of changes in the microbiome during antibiotic administration and discuss specific findings that relate to the impact of anti-tubercular chemotherapy.

RevDate: 2018-12-04

Brenner LA, Hoisington AJ, Stearns-Yoder KA, et al (2018)

Military-Related Exposures, Social Determinants of Health, and Dysbiosis: The United States-Veteran Microbiome Project (US-VMP).

Frontiers in cellular and infection microbiology, 8:400.

Significant effort has been put forth to increase understanding regarding the role of the human microbiome in health- and disease-related processes. In turn, the United States (US) Veteran Microbiome Project (US-VMP) was conceptualized as a means by which to serially collect microbiome and health-related data from those seeking care within the Veterans Health Administration (VHA). In this manuscript, exposures related to military experiences, as well as conditions and health-related factors among patients seen in VHA clinical settings are discussed in relation to common psychological and physical outcomes. Upon enrollment in the study, Veterans complete psychometrically sound (i.e., reliable and valid) measures regarding their past and current medical history. Participants also provide skin, oral, and gut microbiome samples, and permission to track their health status via the VHA electronic medical record. To date, data collection efforts have been cross-diagnostic. Within this manuscript, we describe current data collection practices and procedures, as well as highlight demographic, military, and psychiatric characteristics of the first 188 Veterans enrolled in the study. Based on these findings, we assert that this cohort is unique as compared to those enrolled in recent large-scale studies of the microbiome. To increase understanding regarding disease and health among diverse cohorts, efforts such as the US-VMP are vital. Ongoing barriers and facilitators to data collection are discussed, as well as future research directions, with an emphasis on the importance of shifting current thinking regarding the microbiome from a focus on normalcy and dysbiosis to health promotion and disease prevention.

RevDate: 2018-12-04

Mathias M (2018)

Autointoxication and historical precursors of the microbiome-gut-brain axis.

Microbial ecology in health and disease, 29(2):1548249 pii:1548249.

This article focuses on autointoxication, a discredited medical theory from the late nineteenth century that provides important points of reflection for today's research on the role of microbes in the human gut for mental health. It considers how the theory of autointoxication, which came into great prominence amongst physicians and the general public worldwide, fell from grace by the middle of the twentieth century, and briefly asks why studies of the human microbiome are now back in vogue. It departs from earlier articles on the topic firstly by arguing that autointoxication theory was especially prevalent in France, and secondly by focusing on the application of this theory to mental health. Bringing to light medical treatises and theses from this period which have so far remained unexamined, it shows that examining the development and reception of medical theories form the past can help us today in understanding both the pitfalls and promise of research in this area.

RevDate: 2018-11-29

Ando H (2018)

[Creation of synthetic bacterial viruses].

Nihon saikingaku zasshi. Japanese journal of bacteriology, 73(4):201-210.

Bacteria are closely related with human health and diseases. For example, the emergence of drug-resistant bacteria is a serious problem in the world. Studying the human microbiome shows its important role for our health. But we have very limited tools to edit bacterial population. Antibiotics are generally broad-spectrum and unable to kill only bad bacteria. The natural enemies of bacteria, called bacteriophage (phage), have highly specific host range, and thus promising candidates for targeted bacterial population editing. However, isolation and characterization of natural phages can be a time-, labor- and cost-intensive way. Also, developing phage-based therapeutics and diagnostics is limited by the difficulty of engineering phages. Here, I describe a phage genome-engineering platform and synthetic phages with tunable host ranges to overcome these challenges.

RevDate: 2018-11-28

McCord B, Gauthier Q, Cho S, et al (2018)

Forensic DNA Analysis.

Analytical chemistry [Epub ahead of print].

This review focuses on recent developments in forensic DNA typing. It highlights important recent advances and issues in forensic human identification and identifies representative papers. It is not intended to be comprehensive. The review is divided into several important topic areas. These include developments in forensic serology using RNA, proteomic, and Epigenetic markers, and methods for human identification using short tandem repeats, single nucleotide polymorphisms, and insertion deletions. Sequencing methods for autosomal DNA, sex linked DNA, and mitochondrial DNA are included as well as for the human microbiome. New technologies are also featured, such as real time PCR, microfluidics, integrated rapid PCR systems, and massively parallel sequencing. Expert systems have also been developed to assist with the analysis of data from these complex analytical tools.

RevDate: 2018-11-28

Espinoza JL, Harkins DM, Torralba M, et al (2018)

Supragingival Plaque Microbiome Ecology and Functional Potential in the Context of Health and Disease.

mBio, 9(6): pii:mBio.01631-18.

To address the question of how microbial diversity and function in the oral cavities of children relates to caries diagnosis, we surveyed the supragingival plaque biofilm microbiome in 44 juvenile twin pairs. Using shotgun sequencing, we constructed a genome encyclopedia describing the core supragingival plaque microbiome. Caries phenotypes contained statistically significant enrichments in specific genome abundances and distinct community composition profiles, including strain-level changes. Metabolic pathways that are statistically associated with caries include several sugar-associated phosphotransferase systems, antimicrobial resistance, and metal transport. Numerous closely related previously uncharacterized microbes had substantial variation in central metabolism, including the loss of biosynthetic pathways resulting in auxotrophy, changing the ecological role. We also describe the first complete Gracilibacteria genomes from the human microbiome. Caries is a microbial community metabolic disorder that cannot be described by a single etiology, and our results provide the information needed for next-generation diagnostic tools and therapeutics for caries.IMPORTANCE Oral health has substantial economic importance, with over $100 billion spent on dental care in the United States annually. The microbiome plays a critical role in oral health, yet remains poorly classified. To address the question of how microbial diversity and function in the oral cavities of children relate to caries diagnosis, we surveyed the supragingival plaque biofilm microbiome in 44 juvenile twin pairs. Using shotgun sequencing, we constructed a genome encyclopedia describing the core supragingival plaque microbiome. This unveiled several new previously uncharacterized but ubiquitous microbial lineages in the oral microbiome. Caries is a microbial community metabolic disorder that cannot be described by a single etiology, and our results provide the information needed for next-generation diagnostic tools and therapeutics for caries.


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
21454 NE 143rd Street
Woodinville, WA 98077

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 )