@article {pmid30880022, year = {2019}, author = {Cohen, LJ and Cho, JH and Gevers, D and Chu, H}, title = {Genetic Factors and the Intestinal Microbiome Guide Development of Microbe-based Therapies for Inflammatory Bowel Diseases.}, journal = {Gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.1053/j.gastro.2019.03.017}, pmid = {30880022}, issn = {1528-0012}, abstract = {The intestinal microbiota is a dynamic community of bacteria, fungi, and viruses that mediates mucosal homeostasis and physiology. Imbalances in the microbiome and aberrant immune responses to gut bacteria can disrupt homeostasis and are associated with inflammatory bowel diseases (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.}, } @article {pmid30877283, year = {2019}, author = {Shaw, LP and Bassam, H and Barnes, CP and Walker, AS and Klein, N and Balloux, F}, title = {Modelling microbiome recovery after antibiotics using a stability landscape framework.}, journal = {The ISME journal}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41396-019-0392-1}, pmid = {30877283}, issn = {1751-7370}, support = {EP/F500351/1//RCUK | Engineering and Physical Sciences Research Council (EPSRC)/ ; 097319/Z/11/Z//Wellcome Trust (Wellcome)/ ; }, abstract = {Treatment with antibiotics is one of the most extreme perturbations to the human microbiome. Even standard courses of antibiotics dramatically reduce the microbiome's diversity and can cause transitions to dysbiotic states. Conceptually, this is often described as a 'stability landscape': the microbiome sits in a landscape with multiple stable equilibria, and sufficiently strong perturbations can shift the microbiome from its normal equilibrium to another state. However, this picture is only qualitative and has not been incorporated in previous mathematical models of the effects of antibiotics. Here, we outline a simple quantitative model based on the stability landscape concept and demonstrate its success on real data. Our analytical impulse-response model has minimal assumptions with three parameters. We fit this model in a Bayesian framework to data from a previous study of the year-long effects of short courses of four common antibiotics on the gut and oral microbiomes, allowing us to compare parameters between antibiotics and microbiomes, and further validate our model using data from another study looking at the impact of a combination of last-resort antibiotics on the gut microbiome. Using Bayesian model selection we find support for a long-term transition to an alternative microbiome state after courses of certain antibiotics in both the gut and oral microbiomes. Quantitative stability landscape frameworks are an exciting avenue for future microbiome modelling.}, } @article {pmid30876799, year = {2019}, author = {Douillard, FP and de Vos, WM}, title = {Biotechnology of health-promoting bacteria.}, journal = {Biotechnology advances}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.biotechadv.2019.03.008}, pmid = {30876799}, issn = {1873-1899}, abstract = {Over the last decade, there has been an increasing scientific and public interest in bacteria that may positively contribute to human gut health and well-being. This interest is reflected by the ever-increasing number of developed functional food products containing health-promoting bacteria and reaching the market place as well as by the growing revenue and profits of notably bacterial supplements worldwide. Traditionally, the origin of probiotic-marketed bacteria was limited to a rather small number of bacterial species that mostly belong to lactic acid bacteria and bifidobacteria. Intensifying research efforts on the human gut microbiome offered novel insights into the role of human gut microbiota in health and disease, while also providing a deep and increasingly comprehensive understanding of the bacterial communities present in this complex ecosystem and their interactions with the gut-liver-brain axis. This resulted in rational and systematic approaches to select novel health-promoting bacteria or to engineer existing bacteria with enhanced probiotic properties. In parallel, the field of gut microbiomics developed into a fertile framework for the identification, isolation and characterization of a phylogenetically diverse array of health-promoting bacterial species, also called next-generation therapeutic bacteria. The present review will address these developments with specific attention for the selection and improvement of a selected number of health-promoting bacterial species and strains that are extensively studied or hold promise for future food or pharma product development.}, } @article {pmid30871856, year = {2019}, author = {Minot, SS}, title = {De novo Assembly Vastly Expands the Known Microbial Universe.}, journal = {Trends in microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.tim.2019.02.007}, pmid = {30871856}, issn = {1878-4380}, abstract = {The study of the human microbiome relies heavily on the genomes of bacterial isolates that can be grown in culture. A recent study (Pasolli et al. Cell 2019;176:649-662) of stool microbiome samples generated over 150 000 microbial genomes without any culture, vastly expanding our knowledge of the biases in existing reference databases.}, } @article {pmid30871469, year = {2019}, author = {Perz, AI and Giles, CB and Brown, CA and Porter, H and Roopnarinesingh, X and Wren, JD}, title = {MNEMONIC: MetageNomic Experiment Mining to create an OTU Network of Inhabitant Correlations.}, journal = {BMC bioinformatics}, volume = {20}, number = {Suppl 2}, pages = {96}, doi = {10.1186/s12859-019-2623-x}, pmid = {30871469}, issn = {1471-2105}, abstract = {BACKGROUND: The number of publicly available metagenomic experiments in various environments has been rapidly growing, empowering the potential to identify similar shifts in species abundance between different experiments. This could be a potentially powerful way to interpret new experiments, by identifying common themes and causes behind changes in species abundance.

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.}, } @article {pmid30870464, year = {2019}, author = {Burcham, ZM and Schmidt, CJ and Pechal, JL and Brooks, CP and Rosch, JW and Benbow, ME and Jordan, HR}, title = {Detection of critical antibiotic resistance genes through routine microbiome surveillance.}, journal = {PloS one}, volume = {14}, number = {3}, pages = {e0213280}, doi = {10.1371/journal.pone.0213280}, pmid = {30870464}, issn = {1932-6203}, abstract = {Population-based public health data on antibiotic resistance gene carriage is poorly surveyed. Research of the human microbiome as an antibiotic resistance reservoir has primarily focused on gut associated microbial communities, but data have shown more widespread microbial colonization across organs than originally believed, with organs previously considered as sterile being colonized. Our study demonstrates the utility of postmortem microbiome sampling during routine autopsy as a method to survey antibiotic resistance carriage in a general population. Postmortem microbial sampling detected pathogens of public health concern including genes for multidrug efflux pumps, carbapenem, methicillin, vancomycin, and polymixin resistances. Results suggest that postmortem assessments of host-associated microbial communities are useful in acquiring community specific data while reducing selective-participant biases.}, } @article {pmid30867232, year = {2019}, author = {Elzinga, J and van der Oost, J and de Vos, WM and Smidt, H}, title = {The Use of Defined Microbial Communities To Model Host-Microbe Interactions in the Human Gut.}, journal = {Microbiology and molecular biology reviews : MMBR}, volume = {83}, number = {2}, pages = {}, doi = {10.1128/MMBR.00054-18}, pmid = {30867232}, issn = {1098-5557}, abstract = {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.}, } @article {pmid30863868, year = {2019}, author = {Plantinga, AM and Chen, J and Jenq, RR and Wu, MC}, title = {pldist: ecological dissimilarities for paired and longitudinal microbiome association analysis.}, journal = {Bioinformatics (Oxford, England)}, volume = {}, number = {}, pages = {}, doi = {10.1093/bioinformatics/btz120}, pmid = {30863868}, issn = {1367-4811}, abstract = {MOTIVATION: The human microbiome is notoriously variable across individuals, with a wide range of 'healthy' microbiomes. Paired and longitudinal studies of the microbiome have become increasingly popular as a way to reduce unmeasured confounding and to increase statistical power by reducing large inter-subject variability. Statistical methods for analyzing such datasets are scarce.

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 https://github.com/aplantin/pldist.

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.}, } @article {pmid30848142, year = {2018}, author = {Buchta, V}, title = {Vaginal microbiome.}, journal = {Ceska gynekologie}, volume = {83}, number = {5}, pages = {371-379}, pmid = {30848142}, issn = {1210-7832}, abstract = {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.}, } @article {pmid30843443, year = {2019}, author = {Salvucci, E}, title = {The human-microbiome superorganism and its modulation to restore health.}, journal = {International journal of food sciences and nutrition}, volume = {}, number = {}, pages = {1-15}, doi = {10.1080/09637486.2019.1580682}, pmid = {30843443}, issn = {1465-3478}, abstract = {Microbiome is the community of microorganism that co-live with a host. The human being is the result of the integration of its genome and the coexistence with millions of microorganisms throughout its evolutionary history. Human-microbiome association can be considered a step of integration in evolution, constituting a superorganism. Many emergent diseases are related to the loss of part of this microbiome and its restoration can be achieved by different strategies. Gut microbiome imbalance is particularly associated with numerous inflammatory, immune and nervous system-related diseases by a communication pathway called microbiome-brain axis. Modulation of microbiome by administering prebiotics, like arabinoxylans, and synbiotics is a plausible treatment for dysbiosis, the regulation of neurotransmitters and alleviation of neurological manifestations.}, } @article {pmid30835913, year = {2019}, author = {Rego, S and Dagan-Rosenfeld, O and Bivona, SA and Snyder, MP and Ormond, KE}, title = {Much ado about nothing: A qualitative study of the experiences of an average-risk population receiving results of exome sequencing.}, journal = {Journal of genetic counseling}, volume = {}, number = {}, pages = {}, doi = {10.1002/jgc4.1096}, pmid = {30835913}, issn = {1573-3599}, support = {1U54DE02378901//NIH Common Fund Human Microbiome Project (HMP)/ ; 1-14-TS-28//American Diabetes Association/ ; 1-11-CT-35//American Diabetes Association/ ; }, abstract = {The increasing availability of exome sequencing to the general ("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.}, } @article {pmid30835837, year = {2019}, author = {Haahtela, T}, title = {A Biodiversity Hypothesis.}, journal = {Allergy}, volume = {}, number = {}, pages = {}, doi = {10.1111/all.13763}, pmid = {30835837}, issn = {1398-9995}, abstract = {Biodiversity hypothesis states, that contact with natural environments enriches the human microbiome, promotes immune balance and protects from allergy and inflammatory disorders. We are protected by two nested layers of biodiversity, microbiota of the outer layer (soil, natural waters, plants, animals) and inner layer (gut, skin, airways). The latter inhabits our body and is colonized from the outer layer. Explosion of human populations along with cultural evolution 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.}, } @article {pmid30835680, year = {2019}, author = {Wallace, DJ and Sayre, NL and Patterson, TT and Nicholson, SE and Hilton, D and Grandhi, R}, title = {Spinal cord injury and the human microbiome: beyond the brain-gut axis.}, journal = {Neurosurgical focus}, volume = {46}, number = {3}, pages = {E11}, doi = {10.3171/2018.12.FOCUS18206}, pmid = {30835680}, issn = {1092-0684}, abstract = {In addition to standard management for the treatment of the acute phase of spinal cord injury (SCI), implementation of novel neuroprotective interventions offers the potential for significant reductions in morbidity and long-term health costs. A better understanding of the systemic changes after SCI could provide insight into mechanisms that lead to secondary injury. An emerging area of research involves the complex interplay of the gut microbiome and the CNS, i.e., a brain-gut axis, or perhaps more appropriately, a CNS-gut axis. This review summarizes the relevant literature relating to the gut microbiome and SCI. Experimental models in stroke and traumatic brain injury demonstrate the bidirectional communication of the CNS to the gut with postinjury dysbiosis, gastrointestinal-associated lymphoid tissue-mediated neuroinflammatory responses, and bacterial-metabolite neurotransmission. Similar findings are being elucidated in SCI as well. Experimental interventions in these areas have shown promise in improving functional outcomes in animal models. This commensal relationship between the human body and its microbiome, particularly the gut microbiome, represents an exciting frontier in experimental medicine.}, } @article {pmid30832730, year = {2019}, author = {Meyer, F and Bremges, A and Belmann, P and Janssen, S and McHardy, AC and Koslicki, D}, title = {Assessing taxonomic metagenome profilers with OPAL.}, journal = {Genome biology}, volume = {20}, number = {1}, pages = {51}, doi = {10.1186/s13059-019-1646-y}, pmid = {30832730}, issn = {1474-760X}, abstract = {The explosive growth in taxonomic metagenome profiling methods over the past years has created a need for systematic comparisons using relevant performance criteria. The Open-community Profiling Assessment tooL (OPAL) implements commonly used performance metrics, including those of the first challenge of the initiative for the Critical Assessment of Metagenome Interpretation (CAMI), together with convenient visualizations. In addition, we perform in-depth performance comparisons with seven profilers on datasets of CAMI and the Human Microbiome Project. OPAL is freely available at https://github.com/CAMI-challenge/OPAL .}, } @article {pmid30830433, year = {2019}, author = {Piersigilli, F and Lam, TT and Vernocchi, P and Quagliariello, A and Putignani, L and Aghai, ZH and Bhandari, V}, title = {Identification of new biomarkers of bronchopulmonary dysplasia using metabolomics.}, journal = {Metabolomics : Official journal of the Metabolomic Society}, volume = {15}, number = {2}, pages = {20}, doi = {10.1007/s11306-019-1482-9}, pmid = {30830433}, issn = {1573-3890}, abstract = {OBJECTIVE: To identify new biomarkers of bronchopulmonary dysplasia (BPD) in preterm neonates.

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.}, } @article {pmid30828318, year = {2019}, author = {Reid, G}, title = {Disentangling What We Know About Microbes and Mental Health.}, journal = {Frontiers in endocrinology}, volume = {10}, number = {}, pages = {81}, doi = {10.3389/fendo.2019.00081}, pmid = {30828318}, issn = {1664-2392}, abstract = {Much has been written in recent years about the gut-brain axis. Exciting pilot studies suggest probiotic applications to the gut can reduce anxiety and depression via the vagus nerve. But not to diminish such findings, much still needs to be considered, including the fact that the vagus nerve links to many other body sites that also host a microbiome. Questions remain that touch the core of being human: (i) Do our microbes influence happiness and to what extent? (ii) What components of the gut microbiota and their function, including as it relates to mental health, are critical and how do they differ between agile, fit hunter gatherers and obese westerners or Danes described as the happiest people on the planet? (iii) What role do environmental pollutants play in this microbes-host ecosystem? While approaching life from a reductionist perspective has a long history in science, we need to try to interrogate these health and disease issues from a wider perspective. For verification of a link between the gut microbiota and brain, and to test new therapies, human studies are needed, and are long overdue.}, } @article {pmid30815546, year = {2018}, author = {Wang, Z and Saha, S and Van Horn, S and Thomas, E and Traini, C and Sathe, G and Rajpal, DK and Brown, JR}, title = {Gut microbiome differences between metformin- and liraglutide-treated T2DM subjects.}, journal = {Endocrinology, diabetes & metabolism}, volume = {1}, number = {1}, pages = {e00009}, doi = {10.1002/edm2.9}, pmid = {30815546}, issn = {2398-9238}, abstract = {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.}, } @article {pmid30814984, year = {2019}, author = {Song, Z and Wang, X and Zhou, X and Jiang, S and Li, Y and Ahmad, O and Qi, L and Li, P and Li, J}, title = {Taxonomic Distribution of FosB in Human-Microbiota and Activity Comparison of Fosfomycin Resistance.}, journal = {Frontiers in microbiology}, volume = {10}, number = {}, pages = {200}, doi = {10.3389/fmicb.2019.00200}, pmid = {30814984}, issn = {1664-302X}, abstract = {FosB, a Mg2+ dependent thioltransferase, confers antibiotic resistance to fosfomycin through enzymatic drug inactivation. Among all antibiotic resistant proteins in the Antibiotic Resistance Genes Database and the Comprehensive Antibiotic Resistance Database, FosB is within 5% of the most number of ARPs identified in Human Microbiome Project reference database but mainly distributed in limited genera, i.e., 122 of total 133 FosB homologues are found from Bacillus and Staphylococcus. Furthermore, these FosB sequences could be divided into three clusters based on their phylogenetic relationship, i.e., two groups of FosB were mainly from Bacillus, and another was mainly from Staphylococcus. Finally, we confirmed that FosB from the group of Staphylococcus presented the highest resistance ability to fosfomycin by in silico and in vitro comparisons. In summary, this study elaborates the specific taxonomic characteristics and resistant abilities of FosB in human microbiota, which might help in developing more promising fosfomycin-like antibiotics.}, } @article {pmid30811000, year = {2019}, author = {Shan, Y and Wu, W and Fan, W and Haahtela, T and Zhang, G}, title = {House dust microbiome and human health risks.}, journal = {International microbiology : the official journal of the Spanish Society for Microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1007/s10123-019-00057-5}, pmid = {30811000}, issn = {1139-6709}, abstract = {People spend a lot of time indoors and the indoor microbiome is a major part of the environment that we are exposed to. However, awareness of the exposure to the indoor microbiome and its health effects remains poor. Outdoor environment (soil and air), indoor sources (ventilation, dampness and building materials), human occupants, and pets compose the indoor microbial community. It has been estimated that up to 500-1000 different species can be present in house dust. House dust is a major source and reservoir of indoor microbiome, which influences human microbiome and determines health and disease. Herein, we review the origins and the components of the fungal and bacterial communities in house dust and their possible effect on human health, in particular on allergic disorders, intestinal microbiome, and immune responses. We expect to lay a solid foundation for the further study on the mechanisms of how the house dust microbes interact with the host microbiome and the human immune system.}, } @article {pmid30810508, year = {2019}, author = {Falony, G and Vandeputte, D and Caenepeel, C and Vieira-Silva, S and Daryoush, T and Vermeire, S and Raes, J}, title = {The human microbiome in health and disease: hype or hope.}, journal = {Acta clinica Belgica}, volume = {}, number = {}, pages = {1-12}, doi = {10.1080/17843286.2019.1583782}, pmid = {30810508}, issn = {2295-3337}, abstract = {OBJECTIVES: The prognostic, diagnostic, and therapeutic potential of the human gut microbiota is widely recognised. However, translation of microbiome findings to clinical practice is challenging. Here, we discuss current knowledge and applications in the field.

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.}, } @article {pmid30808411, year = {2019}, author = {, }, title = {A review of 10 years of human microbiome research activities at the US National Institutes of Health, Fiscal Years 2007-2016.}, journal = {Microbiome}, volume = {7}, number = {1}, pages = {31}, doi = {10.1186/s40168-019-0620-y}, pmid = {30808411}, issn = {2049-2618}, abstract = {The National Institutes of Health (NIH) is the primary federal government agency for biomedical research in the USA. NIH provides extensive support for human microbiome research with 21 of 27 NIH Institutes and Centers (ICs) currently funding this area through their extramural research programs. This analysis of the NIH extramural portfolio in human microbiome research briefly reviews the early history of this field at NIH, summarizes the program objectives and the resources developed in the recently completed 10-year (fiscal years 2007-2016) $215 M Human Microbiome Project (HMP) program, evaluates the scope and range of the $728 M NIH investment in extramural human microbiome research activities outside of the HMP over fiscal years 2012-2016, and highlights some specific areas of research which emerged from this investment. This analysis closes with a few comments on the technical needs and knowledge gaps which remain for this field to be able to advance over the next decade and for the outcomes of this research to be able to progress to microbiome-based interventions for treating disease and supporting health.}, } @article {pmid30808401, year = {2019}, author = {, }, title = {2017 NIH-wide workshop report on "The Human Microbiome: Emerging Themes at the Horizon of the 21st Century".}, journal = {Microbiome}, volume = {7}, number = {1}, pages = {32}, doi = {10.1186/s40168-019-0627-4}, pmid = {30808401}, issn = {2049-2618}, support = {U54HD080784//Eunice Kennedy Shriver National Institute of Child Health and Human Development/ ; U54DK102557//National Institute of Diabetes and Digestive and Kidney Diseases/ ; R24DK110499//National Institute of Diabetes and Digestive and Kidney Diseases/ ; U54DE023789//National Institute of Dental and Craniofacial Research/ ; }, abstract = {The National Institutes of Health (NIH) organized a three-day human microbiome research workshop, August 16-18, 2017, to highlight the accomplishments of the 10-year Human Microbiome Project program, the outcomes of the investments made by the 21 NIH Institutes and Centers which now fund this area, and the technical challenges and knowledge gaps which will need to be addressed in order for this field to advance over the next 10 years. This report summarizes the key points in the talks, round table discussions, and Joint Agency Panel from this workshop.}, } @article {pmid30804923, year = {2018}, author = {Ma, Z and Li, L}, title = {Semen Microbiome Biogeography: An Analysis Based on a Chinese Population Study.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {3333}, doi = {10.3389/fmicb.2018.03333}, pmid = {30804923}, issn = {1664-302X}, abstract = {Investigating inter-subject heterogeneity (or spatial distribution) of human semen microbiome diversity is of important significance. Theoretically, the spatial distribution of biodiversity constitutes the core of microbiome biogeography. Practically, the inter-subject heterogeneity is crucial for understanding the normal (healthy) flora of semen microbiotas as well as their possible changes associated with abnormal fertility. In this article, we analyze the scaling (changes) of semen microbiome diversity across individuals with DAR (diversity-area relationship) analysis, a recent extension to classic SAR (species-area relationship) law in biogeography and ecology. Specifically, the unit of "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.}, } @article {pmid30801627, year = {2019}, author = {McSkimming, DI and Banack, HR and Genco, R and Wactawski-Wende, J and LaMonte, MJ}, title = {RE: "QUANTIFICATION OF HUMAN MICROBIOME STABILITY OVER 6 MONTHS: IMPLICATIONS FOR EPIDEMIOLOGIC STUDIES".}, journal = {American journal of epidemiology}, volume = {}, number = {}, pages = {}, doi = {10.1093/aje/kwz021}, pmid = {30801627}, issn = {1476-6256}, } @article {pmid30799264, year = {2019}, author = {De Filippis, F and Pasolli, E and Tett, A and Tarallo, S and Naccarati, A and De Angelis, M and Neviani, E and Cocolin, L and Gobbetti, M and Segata, N and Ercolini, D}, title = {Distinct Genetic and Functional Traits of Human Intestinal Prevotella copri Strains Are Associated with Different Habitual Diets.}, journal = {Cell host & microbe}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.chom.2019.01.004}, pmid = {30799264}, issn = {1934-6069}, abstract = {The role of intestinal Prevotella species in human health is controversial, with both positive and negative associations. Strain-level diversity may contribute to discrepancies in genus and species associations with health and disease. We dissected the gut metagenomes of Italians with varying dietary habits, investigating the presence of distinct Prevotella copri strains. Fiber-rich diets were linked to P. copri types with enhanced potential for carbohydrate catabolism. P. copri strains associated with an omnivore diet had a higher prevalence of the leuB gene-involved in branched-chain amino acid biosynthesis-a risk factor for glucose intolerance and type 2 diabetes. These P. copri pangenomes were compared to existing cohorts, providing evidence of distinct gene repertoires characterizing different P. copri populations, with drug metabolism and complex carbohydrate degradation significantly associated with Western and non-Western individuals, respectively. Strain-level P. copri diversity in gut microbiomes is affected by diet and should be considered when examining host-microbe associations.}, } @article {pmid30799003, year = {2019}, author = {Rogers, GB and Ward, J and Brown, A and Wesselingh, SL}, title = {Inclusivity and equity in human microbiome research.}, journal = {Lancet (London, England)}, volume = {393}, number = {10173}, pages = {728-729}, doi = {10.1016/S0140-6736(18)33204-5}, pmid = {30799003}, issn = {1474-547X}, } @article {pmid30777586, year = {2019}, author = {Araos, R and D'Agata, EMC}, title = {The human microbiota and infection prevention.}, journal = {Infection control and hospital epidemiology}, volume = {}, number = {}, pages = {1-5}, doi = {10.1017/ice.2019.28}, pmid = {30777586}, issn = {1559-6834}, abstract = {The human microbiome participates in numerous aspects of human physiology and disease states. Recently, studies have begun to explore the role of the microbiome in colonization, infection and transmission of pathogens. This review provides a summary of the methodological principles used in microbiome studies and the published evidence of the impact of microbiome dysbiosis in infection prevention.}, } @article {pmid30772579, year = {2019}, author = {Li, H and Zhou, XY and Yang, XR and Zhu, YG and Hong, YW and Su, JQ}, title = {Spatial and seasonal variation of the airborne microbiome in a rapidly developing city of China.}, journal = {The Science of the total environment}, volume = {665}, number = {}, pages = {61-68}, doi = {10.1016/j.scitotenv.2019.01.367}, pmid = {30772579}, issn = {1879-1026}, abstract = {Exposure to airborne microbes (AM) can affect the human microbiome and has various consequences for human health. Investigating the profiles of AM and the potential bacterial pathogens within, along with the factors influencing their community, is pivotal for understanding the impact of AM on human health. In this study, we collected AM during spring and summer from 11 sites with various levels of urbanization in the city of Xiamen, China. Bacterial community compositions of the AM were determined based on 16S rRNA gene amplicon sequencing. Firmicutes and Proteobacteria were the predominating phyla in the airborne bacterial communities, and a higher (P < 0.05) diversity of AM was found during the summer as compared to the spring. Significant differences in the community structure of the AM and the potential bacterial pathogens within airborne microbes were observed among the seasons and the sites with different levels of urbanization. Increases and/or decreases in the abundance of Bacillus and Acinetobacter could explain a major part of the variations in the AM community compositions. The proportion of potential bacterial pathogens during the summer was significantly higher (P < 0.01) than in the spring, and the relative abundance of several bacterial pathogens (i.e. Burkholderia multivoran, Enterococcus faecium and Streptococcus thermophilus) related to human diseases (39.8% of total pathogens on average) increased with increasing urbanization levels, suggesting that urbanization can increase the AM-associated human health risk.}, } @article {pmid30767956, year = {2019}, author = {Bai, J and Jhaney, I and Daniel, G and Watkins Bruner, D}, title = {Pilot Study of Vaginal Microbiome Using QIIME 2™ in Women With Gynecologic Cancer Before and After Radiation Therapy.}, journal = {Oncology nursing forum}, volume = {46}, number = {2}, pages = {E48-E59}, doi = {10.1188/19.ONF.E48-E59}, pmid = {30767956}, issn = {1538-0688}, abstract = {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.}, } @article {pmid30764863, year = {2019}, author = {Luo, Z and Li, M and Wu, Y and Meng, Z and Martin, L and Zhang, L and Ogunrinde, E and Zhou, Z and Qin, S and Wan, Z and Westerink, MAJ and Warth, S and Liu, H and Jin, P and Stroncek, D and Li, QZ and Wang, E and Wu, X and Heath, SL and Li, Z and Alekseyenko, AV and Jiang, W}, title = {Systemic translocation of Staphylococcus drives autoantibody production in HIV disease.}, journal = {Microbiome}, volume = {7}, number = {1}, pages = {25}, doi = {10.1186/s40168-019-0646-1}, pmid = {30764863}, issn = {2049-2618}, support = {AI091526//National Institutes of Health/ ; AI128864//National Institutes of Health/ ; P30 AI027767//National Institutes of Health/ ; AG045973//National Institutes of Health/ ; AI114380//National Institutes of Health/ ; AI114380//National Institutes of Health/ ; CA213290//Foundation for the National Institutes of Health/ ; CX001211//U.S. Department of Veterans Affairs/ ; }, abstract = {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.}, } @article {pmid30763534, year = {2019}, author = {Shkoporov, AN and Hill, C}, title = {Bacteriophages of the Human Gut: The "Known Unknown" of the Microbiome.}, journal = {Cell host & microbe}, volume = {25}, number = {2}, pages = {195-209}, doi = {10.1016/j.chom.2019.01.017}, pmid = {30763534}, issn = {1934-6069}, abstract = {The human gut microbiome is a dense and taxonomically diverse consortium of microorganisms. While the bacterial components of the microbiome have received considerable attention, comparatively little is known about the composition and physiological significance of human gut-associated bacteriophage populations (phageome). By extrapolating our knowledge of phage-host interactions from other environments, one could expect that >1012 viruses reside in the human gut, and we can predict that they play important roles in regulating the complex microbial networks operating in this habitat. Before delving into their function, we need to first overcome the challenges associated with studying and characterizing the phageome. In this Review, we summarize the available methods and main findings regarding taxonomic composition, community structure, and population dynamics in the human gut phageome. We also discuss the main challenges in the field and identify promising avenues for future research.}, } @article {pmid30759766, year = {2019}, author = {Reddel, S and Putignani, L and Del Chierico, F}, title = {The Impact of Low-FODMAPs, Gluten-Free, and Ketogenic Diets on Gut Microbiota Modulation in Pathological Conditions.}, journal = {Nutrients}, volume = {11}, number = {2}, pages = {}, doi = {10.3390/nu11020373}, pmid = {30759766}, issn = {2072-6643}, abstract = {The gut microbiota performs several essential protective, structural, and metabolic functions for host health. The maintenance of a beneficial microbiota requires a homeostatic equilibrium within microbial communities, and between the microorganisms and the host. The gut microbiota composition may be affected by external factors, among them diet habits may be considered most important. In some pathological conditions such as irritable bowel syndrome (IBS), celiac disease (CD), or neurological disorders (ND), specific dietary regimens as low-fermentable, oligo-, di-, mono-saccharides and polyols (FODMAPs), ketogenic (KD), and gluten-free (GFD) diets are considered therapeutic. These kinds of diets are characterized by a reduction or exclusion of a specific nutrient from the entire dietary pattern. Despite these alimentary regimens showing beneficial effects on disease symptoms, they can affect microbiota composition, especially if they are protracted for a long time. To date, only a few studies have reported the effects of these diets on gut microbiota. In this review, we discuss the effects of low-FODMAPs, KD, and GFD on gut microbiota modulation in pathological conditions, advancing the possibility of depicting a balanced diet and developing personalized dietary intervention protocols.}, } @article {pmid30744677, year = {2019}, author = {Blakeley-Ruiz, JA and Erickson, AR and Cantarel, BL and Xiong, W and Adams, R and Jansson, JK and Fraser, CM and Hettich, RL}, title = {Metaproteomics reveals persistent and phylum-redundant metabolic functional stability in adult human gut microbiomes of Crohn's remission patients despite temporal variations in microbial taxa, genomes, and proteomes.}, journal = {Microbiome}, volume = {7}, number = {1}, pages = {18}, doi = {10.1186/s40168-019-0631-8}, pmid = {30744677}, issn = {2049-2618}, support = {UH2DK83991//National Institutes of Health/ ; }, abstract = {BACKGROUND: The gut microbiome plays a fundamental role in the human host's overall health by contributing key biological functions such as expanded metabolism and pathogen defense/immune control. In a healthy individual, the gut microbiome co-exists within the human host in a symbiotic, non-inflammatory relationship that enables mutual benefits, such as microbial degradation of indigestible food products into small molecules that the host can utilize, and enhanced pathogen defense. In abnormal conditions, such as Crohn's disease, this favorable metabolic relationship breaks down and a variety of undesirable activities result, including chronic inflammation and other health-related issues. It has been difficult, however, to elucidate the overall functional characteristics of this relationship because the microbiota can vary substantially in composition for healthy humans and possibly even more in individuals with gut disease conditions such as Crohn's disease. Overall, this suggests that microbial membership composition may not be the best way to characterize a phenotype. Alternatively, it seems to be more informative to examine and characterize the functional composition of a gut microbiome. Towards that end, this study examines 25 metaproteomes measured in several Crohn's disease patients' post-resection surgery across the course of 1 year, in order to examine persistence of microbial taxa, genes, proteins, and metabolic functional distributions across time in individuals whose microbiome might be more variable due to the gut disease condition.

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.}, } @article {pmid30660785, year = {2019}, author = {Marsh, RL and Smith-Vaughan, HC and Chen, ACH and Marchant, JM and Yerkovich, ST and Gibson, PG and Pizzutto, SJ and Hodge, S and Upham, JW and Chang, AB}, title = {Multiple Respiratory Microbiota Profiles Are Associated With Lower Airway Inflammation in Children With Protracted Bacterial Bronchitis.}, journal = {Chest}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.chest.2019.01.002}, pmid = {30660785}, issn = {1931-3543}, abstract = {BACKGROUND: Effective management of protracted bacterial bronchitis (PBB) is needed to prevent chronic disease (eg, bronchiectasis). Understanding the contributions of ongoing airway infection and inflammation is important to achieving optimal PBB treatments. The aim of this study was to compare BAL microbiota, bacterial biomass, and inflammatory markers in children with PBB and age-matched control patients.

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.}, } @article {pmid30732955, year = {2019}, author = {Healy, CM and Moran, GP}, title = {The microbiome and oral cancer: More questions than answers.}, journal = {Oral oncology}, volume = {89}, number = {}, pages = {30-33}, doi = {10.1016/j.oraloncology.2018.12.003}, pmid = {30732955}, issn = {1879-0593}, abstract = {Recent advances in DNA sequencing technology have facilitated rapid advances in the analysis of the human microbiome and its role in human disease. Several studies have now shown that OSCC and some oral premalignant conditions are associated with alterations in the oral microbiome. These studies raise questions regarding the role of the oral microbiome in the progression of oral malignancies and whether microbiome change is a significant risk factor in the development of oral cancer. This short review summarises current knowledge in the field and highlights questions that require further investigation.}, } @article {pmid30731251, year = {2019}, author = {Bekker, V and Zwittink, RD and Knetsch, CW and Sanders, IMJG and Berghuis, D and Heidt, PJ and Vossen, JMJJ and de Vos, WM and Belzer, C and Bredius, RGM and van 't Hof, PJ and Lankester, AC and Kuijper, EJ}, title = {Dynamics of the Gut Microbiota in Children Receiving Selective or Total Gut Decontamination Treatment During Hematopoietic Stem Cell Transplantation.}, journal = {Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.bbmt.2019.01.037}, pmid = {30731251}, issn = {1523-6536}, abstract = {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.}, } @article {pmid30728915, year = {2019}, author = {Lu, H and Ren, Z and Li, A and Li, J and Xu, S and Zhang, H and Jiang, J and Yang, J and Luo, Q and Zhou, K and Zheng, S and Li, L}, title = {Tongue coating microbiome data distinguish patients with pancreatic head cancer from healthy controls.}, journal = {Journal of oral microbiology}, volume = {11}, number = {1}, pages = {1563409}, doi = {10.1080/20002297.2018.1563409}, pmid = {30728915}, issn = {2000-2297}, abstract = {Background: The microbiota plays a critical role in the process of human carcinogenesis. Pancreatic head carcinoma (PHC)-associated tongue coating microbiome dysbiosis has not yet been clearly defined.Objective: Our aim is to reveal the bacterial composition shifts in the microbiota of the tongue coat of PHC patients.Design: The tongue coating microbiota was analyzed in 30 PHC patients and 25 healthy controls using 16S rRNA gene sequencing technology.Results: The microbiome diversity of the tongue coat in PHC patients was significantly increased, as shown by the Shannon, Simpson, inverse Simpson, Obs and incidence-based coverage estimators. Principal component analysis revealed that PHC patients were colonized by remarkably different tongue coating microbiota than healthy controls and liver cancer patients. Linear discriminant analysis effect size revealed that Leptotrichia, Fusobacterium,Rothia, Actinomyces, Corynebacterium, Atopobium, Peptostreptococcus, Catonella, Oribacterium, Filifactor, Campylobacter, Moraxella and Tannerella were overrepresented in the tongue coating of PHC patients, and Haemophilus, Porphyromonas and Paraprevotella were enriched in the tongue coating microbiota of healthy controls. Strikingly, Haemophilus, Porphyromonas, Leptotrichia and Fusobacterium could distinguish PHC patients from healthy subjects, and Streptococcus and SR1 could distinguish PHC patients from liver cancer patients. Conclusions: These findings identified the microbiota dysbiosis of the tongue coat in PHC patients, and provide insight into the association between the human microbiome and pancreatic cancer.}, } @article {pmid30725462, year = {2019}, author = {Morales, E and Chen, J and Greathouse, KL}, title = {Compositional Analysis of the Human Microbiome in Cancer Research.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {1928}, number = {}, pages = {299-335}, doi = {10.1007/978-1-4939-9027-6_16}, pmid = {30725462}, issn = {1940-6029}, abstract = {Gut microbial composition has shown to be associated with obesity, diabetes mellitus, inflammatory bowel disease, colitis, autoimmune disorders, and cancer, among other diseases. Microbiome research has significantly evolved through the years and continues to advance as we develop new and better strategies to more accurately measure its composition and function. Careful selection of study design, inclusion and exclusion criteria of participants, and methodology are paramount to accurately analyze microbial structure. Here we present the most up-to-date available information on methods for gut microbial collection and analysis.}, } @article {pmid30718869, year = {2019}, author = {Forster, SC and Kumar, N and Anonye, BO and Almeida, A and Viciani, E and Stares, MD and Dunn, M and Mkandawire, TT and Zhu, A and Shao, Y and Pike, LJ and Louie, T and Browne, HP and Mitchell, AL and Neville, BA and Finn, RD and Lawley, TD}, title = {A human gut bacterial genome and culture collection for improved metagenomic analyses.}, journal = {Nature biotechnology}, volume = {37}, number = {2}, pages = {186-192}, doi = {10.1038/s41587-018-0009-7}, pmid = {30718869}, issn = {1546-1696}, abstract = {Understanding gut microbiome functions requires cultivated bacteria for experimental validation and reference bacterial genome sequences to interpret metagenome datasets and guide functional analyses. We present the Human Gastrointestinal Bacteria Culture Collection (HBC), a comprehensive set of 737 whole-genome-sequenced bacterial isolates, representing 273 species (105 novel species) from 31 families found in the human gastrointestinal microbiota. The HBC increases the number of bacterial genomes derived from human gastrointestinal microbiota by 37%. The resulting global Human Gastrointestinal Bacteria Genome Collection (HGG) classifies 83% of genera by abundance across 13,490 shotgun-sequenced metagenomic samples, improves taxonomic classification by 61% compared to the Human Microbiome Project (HMP) genome collection and achieves subspecies-level classification for almost 50% of sequences. The improved resource of gastrointestinal bacterial reference sequences circumvents dependence on de novo assembly of metagenomes and enables accurate and cost-effective shotgun metagenomic analyses of human gastrointestinal microbiota.}, } @article {pmid30710104, year = {2019}, author = {Du Toit, A}, title = {Expanding diversity of the human microbiome.}, journal = {Nature reviews. Microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41579-019-0154-0}, pmid = {30710104}, issn = {1740-1534}, } @article {pmid30705670, year = {2018}, author = {Whittle, E and Leonard, MO and Harrison, R and Gant, TW and Tonge, DP}, title = {Multi-Method Characterization of the Human Circulating Microbiome.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {3266}, doi = {10.3389/fmicb.2018.03266}, pmid = {30705670}, issn = {1664-302X}, abstract = {The term microbiome describes the genetic material encoding the various microbial populations that inhabit our body. Whilst colonization of various body niches (e.g., the gut) by dynamic communities of microorganisms is now universally accepted, the existence of microbial populations in other "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.}, } @article {pmid30701191, year = {2019}, author = {Leviatan, S and Segal, E}, title = {A Significant Expansion of Our Understanding of the Composition of the Human Microbiome.}, journal = {mSystems}, volume = {4}, number = {1}, pages = {}, doi = {10.1128/mSystems.00010-19}, pmid = {30701191}, issn = {2379-5077}, abstract = {Shotgun sequencing of samples taken from the human microbiome often reveals only partial mapping of the sequenced metagenomic reads to existing reference genomes. Such partial mappability indicates that many genomes are missing in our reference genome set. This is particularly true for non-Western populations and for samples that do not originate from the gut. Pasolli et al. (E. Pasolli, F. Asnicar, S. Manara, M. Zolfo, et al., Cell, 2019, https://doi.org/10.1016/j.cell.2019.01.001) perform a grand effort to expand the reference set, and to better classify its members, revealing a wider pangenome of existing species as well as identifying new species of previously unknown taxonomic branches.}, } @article {pmid30700742, year = {2019}, author = {Tejesvi, MV and Nissi, R and Saravesi, K and Pirttilä, AM and Markkola, A and Talvensaari-Mattila, A and Ruotsalainen, AL}, title = {Association of prevalent vaginal microbiome of mother with occurrence of type I diabetes in child.}, journal = {Scientific reports}, volume = {9}, number = {1}, pages = {959}, doi = {10.1038/s41598-018-37467-w}, pmid = {30700742}, issn = {2045-2322}, support = {138309//Suomen Akatemia | Biotieteiden ja Ymp&#x00E4;rist&#x00F6;n Tutkimuksen Toimikunta (Research Council for Biosciences and Environment)/ ; }, abstract = {Type I diabetes (T1D) is a rapidly increasing autoimmune disease especially in the Western countries and poses a serious global health problem. Incidence of T1D cannot be fully explained by genetic background, and environmental factors have been assumed to play a role. Environmental conditions and composition of human microbiome have been found to correlate with the incidence of T1D. We asked whether mothers' prevalent vaginal microbiome could correlate with the incidence of T1D in child. To test this hypothesis, we collected samples of vaginal microbiomes from eight mothers that had at least one child with T1D (child age maximum of 11 years at the time of sampling), born with a vaginal delivery. Eight control mothers had child/children with vaginal delivery and no diabetic child/children. The microbiomes were studied by using 16S rRNA Ion Torrent high throughput sequencing. We found that composition of total and Lactobacillus microbiome was altered, and saw an indication that diversity of vaginal microbiomes of the mothers with a diabetic child could be higher. Based on these pilot observations, we strongly encourage a larger population study to verify whether mother vaginal microbiome diversity and composition are linked to the prevalence of T1D in children.}, } @article {pmid30697198, year = {2018}, author = {Naradasu, D and Miran, W and Sakamoto, M and Okamoto, A}, title = {Isolation and Characterization of Human Gut Bacteria Capable of Extracellular Electron Transport by Electrochemical Techniques.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {3267}, doi = {10.3389/fmicb.2018.03267}, pmid = {30697198}, issn = {1664-302X}, abstract = {Microorganisms are known to exhibit extracellular electron transfer (EET) in a wide variety of habitats. However, as for the human microbiome which significantly impacts our health, the role and importance of EET has not been widely investigated. In this study, we enriched and isolated the EET-capable bacteria from human gut microbes using an electrochemical enrichment method and examined whether the isolates couple EET with anaerobic respiration or fermentation. Upon the use of energy-rich or minimum media (with acetate or lactate) for electrochemical enrichment with the human gut sample at an electrode potential of +0.4 V [vs. the standard hydrogen electrode (SHE)], both culture conditions showed significant current production. However, EET-capable pure strains were enriched specifically with minimum media, and subsequent incubation using the δ-MnO2-agar plate with lactate or acetate led to the isolation of two EET-capable microbial strains, Gut-S1 and Gut-S2, having 99% of 16S rRNA gene sequence identity with Enterococcus avium (E. avium) and Klebsiella pneumoniae (K. pneumoniae), respectively. While the enrichment involved anaerobic respiration with acetate and lactate, further electrochemistry with E. avium and K. pneumoniae revealed that the glucose fermentation was also coupled with EET. These results indicate that EET couples not only with anaerobic respiration as found in environmental bacteria, but also with fermentation in the human gut.}, } @article {pmid30692672, year = {2019}, author = {Devoto, AE and Santini, JM and Olm, MR and Anantharaman, K and Munk, P and Tung, J and Archie, EA and Turnbaugh, PJ and Seed, KD and Blekhman, R and Aarestrup, FM and Thomas, BC and Banfield, JF}, title = {Megaphages infect Prevotella and variants are widespread in gut microbiomes.}, journal = {Nature microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41564-018-0338-9}, pmid = {30692672}, issn = {2058-5276}, abstract = {Bacteriophages (phages) dramatically shape microbial community composition, redistribute nutrients via host lysis and drive evolution through horizontal gene transfer. Despite their importance, much remains to be learned about phages in the human microbiome. We investigated the gut microbiomes of humans from Bangladesh and Tanzania, two African baboon social groups and Danish pigs; many of these microbiomes contain phages belonging to a clade with genomes >540 kilobases in length, the largest yet reported in the human microbiome and close to the maximum size ever reported for phages. We refer to these as Lak phages. CRISPR spacer targeting indicates that Lak phages infect bacteria of the genus Prevotella. We manually curated to completion 15 distinct Lak phage genomes recovered from metagenomes. The genomes display several interesting features, including use of an alternative genetic code, large intergenic regions that are highly expressed and up to 35 putative transfer RNAs, some of which contain enigmatic introns. Different individuals have distinct phage genotypes, and shifts in variant frequencies over consecutive sampling days reflect changes in the relative abundance of phage subpopulations. Recent homologous recombination has resulted in extensive genome admixture of nine baboon Lak phage populations. We infer that Lak phages are widespread in gut communities that contain the Prevotella species, and conclude that megaphages, with fascinating and underexplored biology, may be common but largely overlooked components of human and animal gut microbiomes.}, } @article {pmid30689687, year = {2019}, author = {Waldron, L and Schiffer, L and Azhar, R and Ramos, M and Geistlinger, L and Segata, N}, title = {Improving Accessibility of the Human Microbiome Project Data Through Integration With R/Bioconductor.}, journal = {American journal of epidemiology}, volume = {}, number = {}, pages = {}, doi = {10.1093/aje/kwz008}, pmid = {30689687}, issn = {1476-6256}, } @article {pmid30687300, year = {2018}, author = {Woods, DF and Kozak, IM and Flynn, S and O'Gara, F}, title = {The Microbiome of an Active Meat Curing Brine.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {3346}, doi = {10.3389/fmicb.2018.03346}, pmid = {30687300}, issn = {1664-302X}, abstract = {Traditional food products are important to our culture and heritage, and to the continued success of the food industry. Many of the production processes associated with these products have not been subjected to an in-depth microbial compositional analysis. The traditional process of curing meat, both preserves a natural protein source, as well as increasing its organoleptic qualities. One of the most important salting processes is known as Wiltshire curing. The Wiltshire process involves injecting pork with a curing solution and immersing the meat into microbial-rich brine which promotes the development of the distinct organoleptic characteristics. The important microbial component of Wiltshire brine has not been extensively characterized. We analyzed the key microbial component of Wiltshire brine by performing microbiome analysis using Next Generation Sequencing (NGS) technologies. This analysis identified the genera, Marinilactibacillus, Carnobacterium, Leuconostoc, and Vibrio as the core microflora present in Wiltshire curing brine. The important food industrial applications of these bacteria were also assessed. The bacterial diversity of the brine was investigated, and the community composition of the brine was demonstrated to change over time. New knowledge on the characterization of key microbiota associated with a productive Wiltshire brine is an important development linked to promoting enhanced quality and safety of meat processing in the food industry.}, } @article {pmid30687254, year = {2018}, author = {Forbes, JD and Bernstein, CN and Tremlett, H and Van Domselaar, G and Knox, NC}, title = {A Fungal World: Could the Gut Mycobiome Be Involved in Neurological Disease?.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {3249}, doi = {10.3389/fmicb.2018.03249}, pmid = {30687254}, issn = {1664-302X}, abstract = {The human microbiome has received decades of attention from scientific and medical research communities. The human gastrointestinal tract is host to immense populations of microorganisms including bacteria, viruses, archaea, and fungi (the gut microbiota). High-throughput sequencing and computational advancements provide unprecedented ability to investigate the structure and function of microbial communities associated with the human body in health and disease. Most research to date has largely focused on elucidating the bacterial component of the human gut microbiota. Study of the gut "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.}, } @article {pmid30644740, year = {2019}, author = {Brasili, E and Hassimotto, NMA and Del Chierico, F and Marini, F and Quagliariello, A and Sciubba, F and Miccheli, A and Putignani, L and Lajolo, F}, title = {Daily Consumption of Orange Juice from Citrus sinensis L. Osbeck cv. Cara Cara and cv. Bahia Differently Affects Gut Microbiota Profiling as Unveiled by an Integrated Meta-Omics Approach.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.8b05408}, pmid = {30644740}, issn = {1520-5118}, abstract = {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.}, } @article {pmid30675064, year = {2019}, author = {Tanoue, T and Morita, S and Plichta, DR and Skelly, AN and Suda, W and Sugiura, Y and Narushima, S and Vlamakis, H and Motoo, I and Sugita, K and Shiota, A and Takeshita, K and Yasuma-Mitobe, K and Riethmacher, D and Kaisho, T and Norman, JM and Mucida, D and Suematsu, M and Yaguchi, T and Bucci, V and Inoue, T and Kawakami, Y and Olle, B and Roberts, B and Hattori, M and Xavier, RJ and Atarashi, K and Honda, K}, title = {A defined commensal consortium elicits CD8 T cells and anti-cancer immunity.}, journal = {Nature}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41586-019-0878-z}, pmid = {30675064}, issn = {1476-4687}, abstract = {There is a growing appreciation for the importance of the gut microbiota as a therapeutic target in various diseases. However, there are only a handful of known commensal strains that can potentially be used to manipulate host physiological functions. Here we isolate a consortium of 11 bacterial strains from healthy human donor faeces that is capable of robustly inducing interferon-γ-producing CD8 T cells in the intestine. These 11 strains act together to mediate the induction without causing inflammation in a manner that is dependent on CD103+ dendritic cells and major histocompatibility (MHC) class Ia molecules. Colonization of mice with the 11-strain mixture enhances both host resistance against Listeria monocytogenes infection and the therapeutic efficacy of immune checkpoint inhibitors in syngeneic tumour models. The 11 strains primarily represent rare, low-abundance components of the human microbiome, and thus have great potential as broadly effective biotherapeutics.}, } @article {pmid30671046, year = {2018}, author = {Zhang, C and Thakkar, PV and Powell, SE and Sharma, P and Vennelaganti, S and Betel, D and Shah, MA}, title = {A Comparison of Homogenization vs. Enzymatic Lysis for Microbiome Profiling in Clinical Endoscopic Biopsy Tissue Samples.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {3246}, doi = {10.3389/fmicb.2018.03246}, pmid = {30671046}, issn = {1664-302X}, abstract = {Identification of the human microbiome has proven to be of utmost importance with the emerging role of bacteria in various physiological and pathological processes. High throughput sequencing strategies have evolved to assess the composition of the microbiome. To identify possible bias that may exist in the processing of tissue for whole genome sequencing (WGS), it is important to evaluate the extraction method on the overall microbial content and composition. Here we compare two different methods of extraction, homogenization vs. enzymatic lysis, on gastric, esophageal and colorectal biopsies and survey the microbial content and composition using WGS and quantitative PCR (qPCR). We examined total bacterial content using universal 16S rDNA qPCR as well as the abundance of three phyla (Actinobacter, Firmicutes, Bacteroidetes) and one genus (Fusobacterium). We found minimal differences between the two extraction methods in the overall community structure. Furthermore, based on our qPCR analysis, neither method demonstrated preferential extraction of any particular clade of bacteria, nor significantly altered the detection of Gram-positive or Gram-negative organisms. However, although the overall microbial composition remained very similar and the most prevalent bacteria could be detected effectively using either method, the precise community structure and microbial abundances between the two methods were different, primarily due to variations in detection of low abundance genus. We also demonstrate that the homogenization extraction method provides higher microbial DNA content and higher read counts from human tissue biopsy samples of the gastrointestinal tract.}, } @article {pmid30670574, year = {2019}, author = {Dominguez-Bello, MG and Godoy-Vitorino, F and Knight, R and Blaser, MJ}, title = {Role of the microbiome in human development.}, journal = {Gut}, volume = {}, number = {}, pages = {}, doi = {10.1136/gutjnl-2018-317503}, pmid = {30670574}, issn = {1468-3288}, abstract = {The host-microbiome supraorganism appears to have coevolved and the unperturbed microbial component of the dyad renders host health sustainable. This coevolution has likely shaped evolving phenotypes in all life forms on this predominantly microbial planet. The microbiota seems to exert effects on the next generation from gestation, via maternal microbiota and immune responses. The microbiota ecosystems develop, restricted to their epithelial niches by the host immune system, concomitantly with the host chronological development, providing early modulation of physiological host development and functions for nutrition, immunity and resistance to pathogens at all ages. Here, we review the role of the microbiome in human development, including evolutionary considerations, and the maternal/fetal relationships, contributions to nutrition and growth. We also discuss what constitutes a healthy microbiota, how antimicrobial modern practices are impacting the human microbiota, the associations between microbiota perturbations, host responses and diseases rocketing in urban societies and potential for future restoration.}, } @article {pmid30666529, year = {2018}, author = {Bilen, M and Fonkou, MDM and Caputo, A and Nguyen, TT and Di Pinto, F and Bittar, F and Daoud, Z and Levasseur, A and Fournier, PE and Raoult, D and Cadoret, F}, title = {Phoenicibacter congonensis gen. nov., sp. nov., a new genus isolated from the human gut and its description using a taxonogenomic approach.}, journal = {Antonie van Leeuwenhoek}, volume = {}, number = {}, pages = {}, doi = {10.1007/s10482-018-01211-1}, pmid = {30666529}, issn = {1572-9699}, support = {10-IAHU- 03//Agence Nationale de la Recherche/ ; FEDER PRIMI//Conseil R?gional Provence-Alpes-C?te d'Azur/ ; }, abstract = {Culturomics has recently allowed the isolation and description of previously uncultured bacteria from the human microbiome at different body sites. As part of a project aiming to describe the human gut microbiota by culturomics, Phoenicibacter congonensis strain Marseille-P3241T was isolated from the gut of a 45 years old Pygmy female. In the present work, we aim to describe this strain via the taxonogenomics approach. The major phenotypic, genomic and biochemical characteristics of this strain were analysed. Strain Marseille-P3241T is an anaerobic, Gram-positive and motile coccobacillus that grows optimally at 37 °C. The genome of strain Marseille-P3241T is 1,447,956 bp long with 43.44% GC content and its 16S rRNA gene sequence exhibited 89% sequence similarity with that of Denitrobacterium detoxificans strain NPOH1T, the phylogenetically closest related species with current standing in nomenclature. After performing a phylogenetic and genomic analysis, we conclude that strain Marseille-P3241T (= CCUG 70681T = CSUR P3241T) represents the type species of a new genus, for which we propose the name Phoenicibacter congonensis gen. nov., sp. nov.}, } @article {pmid30666248, year = {2018}, author = {Malla, MA and Dubey, A and Kumar, A and Yadav, S and Hashem, A and Abd Allah, EF}, title = {Exploring the Human Microbiome: The Potential Future Role of Next-Generation Sequencing in Disease Diagnosis and Treatment.}, journal = {Frontiers in immunology}, volume = {9}, number = {}, pages = {2868}, doi = {10.3389/fimmu.2018.02868}, pmid = {30666248}, issn = {1664-3224}, abstract = {The interaction between the human microbiome and immune system has an effect on several human metabolic functions and impacts our well-being. Additionally, the interaction between humans and microbes can also play a key role in determining the wellness or disease status of the human body. Dysbiosis is related to a plethora of diseases, including skin, inflammatory, metabolic, and neurological disorders. A better understanding of the host-microbe interaction is essential for determining the diagnosis and appropriate treatment of these ailments. The significance of the microbiome on host health has led to the emergence of new therapeutic approaches focused on the prescribed manipulation of the host microbiome, either by removing harmful taxa or reinstating missing beneficial taxa and the functional roles they perform. Culturing large numbers of microbial taxa in the laboratory is problematic at best, if not impossible. Consequently, this makes it very difficult to comprehensively catalog the individual members comprising a specific microbiome, as well as understanding how microbial communities function and influence host-pathogen interactions. Recent advances in sequencing technologies and computational tools have allowed an increasing number of metagenomic studies to be performed. These studies have provided key insights into the human microbiome and a host of other microbial communities in other environments. In the present review, the role of the microbiome as a therapeutic agent and its significance in human health and disease is discussed. Advances in high-throughput sequencing technologies for surveying host-microbe interactions are also discussed. Additionally, the correlation between the composition of the microbiome and infectious diseases as described in previously reported studies is covered as well. Lastly, recent advances in state-of-the-art bioinformatics software, workflows, and applications for analysing metagenomic data are summarized.}, } @article {pmid30664484, year = {2019}, author = {Lauwers, L and Bastiaens, H and Remmen, R and Keune, H}, title = {The Integration of Interlinkages Between Nature and Human Health in Primary Health Care: Protocol for a Scoping Review.}, journal = {JMIR research protocols}, volume = {8}, number = {1}, pages = {e12510}, doi = {10.2196/12510}, pmid = {30664484}, issn = {1929-0748}, abstract = {BACKGROUND: International overview reports and the majority of scientific publications on interlinkages between nature and human health (NHI) do not seem to focus on the role of the health care sector. Primary health care (PHC) is often the first point of contact people have with the health care system and provides comprehensive, accessible, and community-based care that meets the health needs of individuals throughout their life. PHC is a vital backbone for linking knowledge and practice within the organization of health care. This scoping review aims to focus on the potential role of PHC in relation to NHI.

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.

DERR1-10.2196/12510.}, } @article {pmid30664014, year = {2019}, author = {Joris, BR and Gloor, GB}, title = {Unaccounted risk of cardiovascular disease: the role of the microbiome in lipid metabolism.}, journal = {Current opinion in lipidology}, volume = {}, number = {}, pages = {}, doi = {10.1097/MOL.0000000000000582}, pmid = {30664014}, issn = {1473-6535}, abstract = {PURPOSE OF REVIEW: Not all of the risk of cardiovascular disease can be explained by diet and genetics, and the human microbiome, which lies at the interface of these two factors, may help explain some of the unaccounted risk. This review examines some of the well established links between the microbiome and cardiovascular health, and proposes relatively unexplored associations.

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.}, } @article {pmid30661755, year = {2019}, author = {Pasolli, E and Asnicar, F and Manara, S and Zolfo, M and Karcher, N and Armanini, F and Beghini, F and Manghi, P and Tett, A and Ghensi, P and Collado, MC and Rice, BL and DuLong, C and Morgan, XC and Golden, CD and Quince, C and Huttenhower, C and Segata, N}, title = {Extensive Unexplored Human Microbiome Diversity Revealed by Over 150,000 Genomes from Metagenomes Spanning Age, Geography, and Lifestyle.}, journal = {Cell}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.cell.2019.01.001}, pmid = {30661755}, issn = {1097-4172}, abstract = {The body-wide human microbiome plays a role in health, but its full diversity remains uncharacterized, particularly outside of the gut and in international populations. We leveraged 9,428 metagenomes to reconstruct 154,723 microbial genomes (45% of high quality) spanning body sites, ages, countries, and lifestyles. We recapitulated 4,930 species-level genome bins (SGBs), 77% without genomes in public repositories (unknown SGBs [uSGBs]). uSGBs are prevalent (in 93% of well-assembled samples), expand underrepresented phyla, and are enriched in non-Westernized populations (40% of the total SGBs). We annotated 2.85 M genes in SGBs, many associated with conditions including infant development (94,000) or Westernization (106,000). SGBs and uSGBs permit deeper microbiome analyses and increase the average mappability of metagenomic reads from 67.76% to 87.51% in the gut (median 94.26%) and 65.14% to 82.34% in the mouth. We thus identify thousands of microbial genomes from yet-to-be-named species, expand the pangenomes of human-associated microbes, and allow better exploitation of metagenomic technologies.}, } @article {pmid30658055, year = {2019}, author = {Pellock, SJ and Walton, WG and Ervin, SM and Torres-Rivera, D and Creekmore, BC and Bergan, G and Dunn, ZD and Li, B and Tripathy, A and Redinbo, MR}, title = {Discovery and Characterization of FMN-Binding β-Glucuronidases in the Human Gut Microbiome.}, journal = {Journal of molecular biology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jmb.2019.01.013}, pmid = {30658055}, issn = {1089-8638}, abstract = {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.}, } @article {pmid30657195, year = {2019}, author = {Espin-Garcia, O and Croitoru, K and Xu, W}, title = {A finite mixture model for X-chromosome association with an emphasis on microbiome data analysis.}, journal = {Genetic epidemiology}, volume = {}, number = {}, pages = {}, doi = {10.1002/gepi.22190}, pmid = {30657195}, issn = {1098-2272}, support = {RGPIN-2017-06672//Natural Sciences and Engineering Research Council of Canada/ ; 145546//Canadian Institutes of Health Research/Canada ; GET-101831//Canadian Institutes of Health Research/Canada ; CMF108031//Canadian Institutes of Health Research/Canada ; //Crohn's and Colitis Canada Grant CCC-GEMIII/ ; //Helmsley Charitable Trust/ ; }, abstract = {Analysis of the X chromosome has been largely neglected in genetic studies mainly because of complex underlying biological mechanisms. On the other hand, the study of human microbiome data (typically over-dispersed counts with an excess of zeros) has generated great interest recently because of advancements in next-generation sequencing technologies. We propose a novel approach to infer the association between host genetic variants in the X-chromosome and microbiome data. The method accounts for random X-chromosome inactivation (XCI), skewed (or nonrandom) XCI (XCI-S), and escape of XCI (XCI-E). The inference is performed through a finite mixture model (FMM), in which an indicator variable denoting the "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.}, } @article {pmid30650377, year = {2019}, author = {Britton, GJ and Contijoch, EJ and Mogno, I and Vennaro, OH and Llewellyn, SR and Ng, R and Li, Z and Mortha, A and Merad, M and Das, A and Gevers, D and McGovern, DPB and Singh, N and Braun, J and Jacobs, JP and Clemente, JC and Grinspan, A and Sands, BE and Colombel, JF and Dubinsky, MC and Faith, JJ}, title = {Microbiotas from Humans with Inflammatory Bowel Disease Alter the Balance of Gut Th17 and RORγt+ Regulatory T Cells and Exacerbate Colitis in Mice.}, journal = {Immunity}, volume = {50}, number = {1}, pages = {212-224.e4}, doi = {10.1016/j.immuni.2018.12.015}, pmid = {30650377}, issn = {1097-4180}, abstract = {Microbiota are thought to influence the development and progression of inflammatory bowel disease (IBD), but determining generalizable effects of microbiota on IBD etiology requires larger-scale functional analyses. We colonized germ-free mice with intestinal microbiotas from 30 healthy and IBD donors and determined the homeostatic intestinal T cell response to each microbiota. Compared to microbiotas from healthy donors, transfer of IBD microbiotas into germ-free mice increased numbers of intestinal Th17 cells and Th2 cells and decreased numbers of RORγt+ Treg cells. Colonization with IBD microbiotas exacerbated disease in a model where colitis is induced upon transfer of naive T cells into Rag1-/- mice. The proportions of Th17 and RORγt+ Treg cells induced by each microbiota were predictive of human disease status and accounted for disease severity in the Rag1-/- colitis model. Thus, an impact on intestinal Th17 and RORγt+ Treg cell compartments emerges as a unifying feature of IBD microbiotas, suggesting a general mechanism for microbial contribution to IBD pathogenesis.}, } @article {pmid30649168, year = {2019}, author = {Griffith, JC and Morgan, XC}, title = {Invited Commentary: Improving accessibility of the Human Microbiome Project data through integration with R/Bioconductor.}, journal = {American journal of epidemiology}, volume = {}, number = {}, pages = {}, doi = {10.1093/aje/kwz007}, pmid = {30649168}, issn = {1476-6256}, abstract = {Alterations in the composition of the microbiota have been implicated in many diseases. The Human Microbiome Project (HMP) provides a comprehensive reference 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.}, } @article {pmid30649166, year = {2019}, author = {Schiffer, L and Azhar, R and Shepherd, L and Ramos, M and Geistlinger, L and Huttenhower, C and Dowd, JB and Segata, N and Waldron, L}, title = {HMP16SData: Efficient Access to the Human Microbiome Project through Bioconductor.}, journal = {American journal of epidemiology}, volume = {}, number = {}, pages = {}, doi = {10.1093/aje/kwz006}, pmid = {30649166}, issn = {1476-6256}, abstract = {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.}, } @article {pmid30649062, year = {2019}, author = {Sessa, L and Reddel, S and Manno, E and Quagliariello, A and Cotugno, N and Del Chierico, F and Amodio, D and Capponi, C and Leone, F and Bernardi, S and Rossi, P and Putignani, L and Palma, P}, title = {Distinct gut microbiota profile in ART-treated perinatally HIV-infected patients associated with cardiac and inflammatory biomarkers.}, journal = {AIDS (London, England)}, volume = {}, number = {}, pages = {}, doi = {10.1097/QAD.0000000000002131}, pmid = {30649062}, issn = {1473-5571}, abstract = {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.}, } @article {pmid30643895, year = {2019}, author = {Gutiérrez-Barranquero, JA and Parages, ML and Dobson, ADW and Reen, FJ and O'Gara, F}, title = {Genome Sequence of Paracoccus sp. JM45, a Bacterial Strain Isolated from a Marine Sponge with a Dual Quorum Sensing Inhibition Activity.}, journal = {Microbiology resource announcements}, volume = {8}, number = {2}, pages = {}, doi = {10.1128/MRA.01496-18}, pmid = {30643895}, issn = {2576-098X}, abstract = {The draft genome sequence of Paracoccus sp. strain JM45, isolated from a marine sponge harvested off the west coast of Ireland, is reported here. Quorum sensing and quorum sensing inhibition activities have been reported recently for this bacterium, and genomic analysis supports its potential use for novel therapeutic development.}, } @article {pmid30635376, year = {2019}, author = {Feng, S and McLellan, SL}, title = {Highly specific sewage-derived Bacteroides qPCR assays target sewage polluted waters.}, journal = {Applied and environmental microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1128/AEM.02696-18}, pmid = {30635376}, issn = {1098-5336}, abstract = {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.}, } @article {pmid30626617, year = {2019}, author = {Rowan-Nash, AD and Korry, BJ and Mylonakis, E and Belenky, P}, title = {Cross-Domain and Viral Interactions in the Microbiome.}, journal = {Microbiology and molecular biology reviews : MMBR}, volume = {83}, number = {1}, pages = {}, doi = {10.1128/MMBR.00044-18}, pmid = {30626617}, issn = {1098-5557}, abstract = {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.}, } @article {pmid30619299, year = {2018}, author = {Satitsuksanoa, P and Jansen, K and Głobińska, A and van de Veen, W and Akdis, M}, title = {Regulatory Immune Mechanisms in Tolerance to Food Allergy.}, journal = {Frontiers in immunology}, volume = {9}, number = {}, pages = {2939}, doi = {10.3389/fimmu.2018.02939}, pmid = {30619299}, issn = {1664-3224}, abstract = {Oral tolerance can develop after frequent exposure to food allergens. Upon ingestion, food is digested into small protein fragments in the gastrointestinal tract. Small food particles are later absorbed into the human body. Interestingly, some of these ingested food proteins can cause allergic immune responses, which can lead to food allergy. So far it has not been completely elucidated how these proteins become immunogenic and cause food allergies. In contrast, oral tolerance helps to prevent the pathologic reactions against different types of food antigens from animal or plant origin. Tolerance to food is mainly acquired by dendritic cells, epithelial cells in the gut, and the gut microbiome. A subset of CD103+ DCs is capable of inducing T regulatory cells (Treg cells) that express anti-inflammatory cytokines. Anergic T cells also contribute to oral tolerance, by reducing the number of effector cells. Similar to Treg cells, B regulatory cells (Breg cells) suppress effector T cells and contribute to the immune tolerance to food allergens. Furthermore, the human microbiome is an essential mediator in the induction of oral tolerance or food allergy. In this review, we outline the current understanding of regulatory immune mechanisms in oral tolerance. The biological changes reflecting early consequences of immune stimulation with food allergens should provide useful information for the development of novel therapeutic treatments.}, } @article {pmid30619188, year = {2018}, author = {Xiao, J and Chen, L and Yu, Y and Zhang, X and Chen, J}, title = {A Phylogeny-Regularized Sparse Regression Model for Predictive Modeling of Microbial Community Data.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {3112}, doi = {10.3389/fmicb.2018.03112}, pmid = {30619188}, issn = {1664-302X}, abstract = {Fueled by technological advancement, there has been a surge of human microbiome studies surveying the microbial communities associated with the human body and their links with health and disease. As a complement to the human genome, the human microbiome holds great potential for precision medicine. Efficient predictive models based on microbiome data could be potentially used in various clinical applications such as disease diagnosis, patient stratification and drug response prediction. One important characteristic of the microbial community data is the phylogenetic tree that relates all the microbial taxa based on their evolutionary history. The phylogenetic tree is an informative prior for more efficient prediction since the microbial community changes are usually not randomly distributed on the tree but tend to occur in clades at varying phylogenetic depths (clustered signal). Although community-wide changes are possible for some conditions, it is also likely that the community changes are only associated with a small subset of "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.}, } @article {pmid30604388, year = {2019}, author = {Osman, AEG and Luke, JJ}, title = {The Impact of the Fecal Microbiome on Cancer Immunotherapy.}, journal = {BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy}, volume = {}, number = {}, pages = {}, doi = {10.1007/s40259-018-0328-8}, pmid = {30604388}, issn = {1179-190X}, support = {W81XWH-17-1-0265//U.S. Department of Defense/ ; }, abstract = {Recent advances in culture-free methods of studying the human microbiome, coupled with strong bioinformatics tools, have provided new insights on the role of the human microbiome in health and disease. The human gut, in particular, houses a vast number and diverse variety of microbes. A plethora of evidence has demonstrated the significant effects of the gut microbiome on local and systemic immunity. Studies in hematopoietic stem cell transplantation recipients provided early evidence of the involvement of the gut microbiome in the development of graft-versus-host disease and its related mortality. Cancer immunotherapy and checkpoint inhibitors, in particular, harness the power of the host's immune system to fight a range of malignancies. Resistance to immunotherapy and fatal immune-related adverse events both continue to be challenges in the field. The role of the human gut microbiome in affecting the response to immunotherapy was recently uncovered through a series of preclinical and clinical studies. The evidence presented in these studies provides tremendous potential for gut microbes to be used for biomarker development and therapeutic intervention trials.}, } @article {pmid30592383, year = {2018}, author = {van Dijkhuizen, EHP and Del Chierico, F and Malattia, C and Russo, A and Pires Marafon, D and Ter Haar, NM and Magni-Manzoni, S and Vastert, SJ and Dallapiccola, B and Prakken, B and Martini, A and De Benedetti, F and Putignani, L and , }, title = {Microbiome analytics of the gut microbiota in juvenile idiopathic arthritis patients: an observational, longitudinal cohort study.}, journal = {Arthritis & rheumatology (Hoboken, N.J.)}, volume = {}, number = {}, pages = {}, doi = {10.1002/art.40827}, pmid = {30592383}, issn = {2326-5205}, abstract = {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.}, } @article {pmid30588567, year = {2018}, author = {Wei, F and Wu, Q and Hu, Y and Huang, G and Nie, Y and Yan, L}, title = {Conservation metagenomics: a new branch of conservation biology.}, journal = {Science China. Life sciences}, volume = {}, number = {}, pages = {}, doi = {10.1007/s11427-018-9423-3}, pmid = {30588567}, issn = {1869-1889}, abstract = {Multifaceted approaches are required to monitor wildlife populations and improve conservation efforts. In the last decade, increasing evidence suggests that metagenomic analysis offers valuable perspectives and tools for identifying microbial communities and functions. It has become clear that gut microbiome plays a critical role in health, nutrition, and physiology of wildlife, including numerous endangered animals in the wild and in captivity. In this review, we first introduce the human microbiome and metagenomics, highlighting the importance of microbiome for host fitness. Then, for the first time, we propose the concept of conservation metagenomics, an emerging subdiscipline of conservation biology, which aims to understand the roles of the microbiota in evolution and conservation of endangered animals. We define what conservation metagenomics is along with current approaches, main scientific issues and significant implications in the study of host evolution, physiology, nutrition, ecology and conservation. We also discuss future research directions of conservation metagenomics. Although there is still a long way to go, conservation metagenomics has already shown a significant potential for improving the conservation and management of wildlife.}, } @article {pmid30584647, year = {2018}, author = {Zhang, J and Zhang, F and Zhao, C and Xu, Q and Liang, C and Yang, Y and Wang, H and Shang, Y and Wang, Y and Mu, X and Zhu, D and Zhang, C and Yang, J and Yao, M and Zhang, L}, title = {Dysbiosis of the gut microbiome is associated with thyroid cancer and thyroid nodules and correlated with clinical index of thyroid function.}, journal = {Endocrine}, volume = {}, number = {}, pages = {}, doi = {10.1007/s12020-018-1831-x}, pmid = {30584647}, issn = {1559-0100}, support = {31471202//the National Natural Science Foundation of China/ ; 81670822//the National Natural Science Foundation of China/ ; 2016YYSP009//the Shandong Provincial Key Research and Development Program/ ; 2016GNS023//Weihai Technique Extension Project/ ; 17-3-3-10-nsh//Qingdao Key Research Project/ ; tshw20120206//the Taishan Scholars Program of Shandong Province/ ; }, abstract = {PURPOSE: Thyroid cancer and thyroid nodules are the most prevalent form of thyroid endocrine disorder. The balance of gut microbiome is highly crucial for a healthy human body, especially for the immune and endocrine system. However, the relationship between gut microbiome and the thyroid endocrine disorders such as thyroid cancer and thyroid nodules has not been reported yet.

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.}, } @article {pmid30578461, year = {2018}, author = {Nobili, V and Mosca, A and Alterio, T and Cardile, S and Putignani, L}, title = {Fighting Fatty Liver Diseases with Nutritional Interventions, Probiotics, Symbiotics, and Fecal Microbiota Transplantation (FMT).}, journal = {Advances in experimental medicine and biology}, volume = {}, number = {}, pages = {}, doi = {10.1007/5584_2018_318}, pmid = {30578461}, issn = {0065-2598}, abstract = {Pediatric obesity is rising worldwide leading the worrying phenomenon of nonalcoholic fatty liver disease (NAFLD) to shift into one of the most frequent causes of chronic liver illness in childhood. Occurrence of NAFLD depends on several factors such as the geographical area and the diagnostic modalities used; overall it ranges between 3% and 10% of pediatric population, increasing up to 70% in patients with metabolic comorbidities (Manco M, Bottazzo G, DeVito R et al, J Am Coll Nutr 27:667-676, 2008).Recent findings have related the intestinal microbiota to a plethora of pathological conditions, including type 2 diabetes (T2D), obesity, and nonalcoholic steatohepatitis (NASH). One of the emerging areas of the study is the link between liver diseases and gut microbiome, which has added new information to the understanding of the so-called gut-liver axis.In order to address the role of gut microbiome in NAFLD onset and progression, it is necessary to "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.}, } @article {pmid30578265, year = {2018}, author = {Stubbendieck, RM and May, DS and Chevrette, MG and Temkin, MI and Wendt-Pienkowski, E and Cagnazzo, J and Carlson, CM and Gern, JE and Currie, CR}, title = {Competition among nasal bacteria suggests a role for siderophore-mediated interactions in shaping the human nasal microbiota.}, journal = {Applied and environmental microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1128/AEM.02406-18}, pmid = {30578265}, issn = {1098-5336}, abstract = {Resources available in the human nasal cavity are limited. Therefore, to successfully colonize the nasal cavity, bacteria must compete for scarce nutrients. Competition may occur directly through interference (e.g., antibiotics) or indirectly by nutrient sequestration. To investigate the nature of nasal bacterial competition, we performed 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.}, } @article {pmid30577530, year = {2018}, author = {Yang, AJ and Marito, S and Yang, JJ and Keshari, S and Chew, CH and Chen, CC and Huang, CM}, title = {A Microtube Array Membrane (MTAM) Encapsulated Live Fermenting Staphylococcus epidermidis as a Skin Probiotic Patch against Cutibacterium acnes.}, journal = {International journal of molecular sciences}, volume = {20}, number = {1}, pages = {}, doi = {10.3390/ijms20010014}, pmid = {30577530}, issn = {1422-0067}, support = {106-2320-B-008, 105-2314-B-008-001, 101-2221-E-038-009-, 107-2314-B-008 -001, 107-2622-B-008-002-CC1 and 106/107-2622-B-008-001-CC1//Ministry of Science and Technology, Taiwan/ ; NHRI-EX106-10607SI//NHRI/ ; }, abstract = {Antibiotics without selectivity for acne treatment may destroy the beneficial microbes in the human microbiome that helps to fight Cutibacterium acnes (C. acnes), a bacterium associated with inflammatory acne vulgaris. Probiotic treatment by direct application of live Staphylococcus epidermidis (S. epidermidis) onto the open acne lesions may run the risk of bloodstream infections. Here, we fabricated the polysulfone microtube array membranes (PSF MTAM) to encapsulate probiotic S.epidermidis. We demonstrate that the application of the encapsulation of S.epidermidis in PSF MTAM enhanced the glycerol fermentation activities of S. epidermidis. To mimic the granulomatous type of acne inflammatory acne vulgaris, the ears of mice were injected intradermally with C.acnes to induce the secretion of macrophage inflammatory protein-2 (MIP-2), a murine counterpart of human interleukin (IL)-8. The C. acnes-injected mouse ears were covered with a PST MTAM encapsulated with or without S.epidermidis in the presence of glycerol. The application of S.epidermidis-encapsulated PST MTAM plus glycerol onto the C.acnes-injected mouse ears considerably reduced the growth of C. acnes and the production of MIP-2. Furthermore, no S. epidermidis leaked from PSF MTAM into mouse skin. The S. epidermidis-encapsulated PST MTAM functions as a probiotic acne patch.}, } @article {pmid30575732, year = {2018}, author = {Coryell, M and McAlpine, M and Pinkham, NV and McDermott, TR and Walk, ST}, title = {The gut microbiome is required for full protection against acute arsenic toxicity in mouse models.}, journal = {Nature communications}, volume = {9}, number = {1}, pages = {5424}, doi = {10.1038/s41467-018-07803-9}, pmid = {30575732}, issn = {2041-1723}, abstract = {Arsenic poisons an estimated 200 million people worldwide through contaminated food and drinking water. Confusingly, the gut microbiome has been suggested to both mitigate and exacerbate arsenic toxicity. Here, we show that the microbiome protects mice from arsenic-induced mortality. Both antibiotic-treated and germ-free mice excrete less arsenic in stool and accumulate more arsenic in organs compared to control mice. Mice lacking the primary arsenic detoxification enzyme (As3mt) are hypersensitive to arsenic after antibiotic treatment or when derived germ-free, compared to wild-type and/or conventional counterparts. Human microbiome (stool) transplants protect germ-free As3mt-KO mice from arsenic-induced mortality, but protection depends on microbiome stability and the presence of specific bacteria, including Faecalibacterium. Our results demonstrate that both a functional As3mt and specific microbiome members are required for protection against acute arsenic toxicity in mouse models. We anticipate that the gut microbiome will become an important explanatory factor of disease (arsenicosis) penetrance in humans, and a novel target for prevention and treatment strategies.}, } @article {pmid30573380, year = {2018}, author = {Altomare, A and Putignani, L and Del Chierico, F and Cocca, S and Angeletti, S and Ciccozzi, M and Tripiciano, C and Dalla Piccola, B and Cicala, M and Guarino, MPL}, title = {Gut mucosal-associated microbiota better discloses Inflammatory Bowel Disease differential patterns than faecal microbiota.}, journal = {Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.dld.2018.11.021}, pmid = {30573380}, issn = {1878-3562}, abstract = {BACKGROUND: Growing evidence supports the potential role of intestinal microbiota in the pathophysiology of Inflammatory Bowel Diseases (IBD) even if the literature does not reveal uniform alterations. The aim of the study was to evaluate the mucosal (MM) and faecal microbiota (FM) composition in a cohort of IBD patients compared to healthy controls (CTRLs).

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.}, } @article {pmid30572622, year = {2018}, author = {Sánchez-Ponce, Y and Varela-Fascinetto, G and Romo-Vázquez, JC and López-Martínez, B and Sánchez-Huerta, JL and Parra-Ortega, I and Fuentes-Pananá, EM and Morales-Sánchez, A}, title = {Simultaneous Detection of Beta and Gamma Human Herpesviruses by Multiplex qPCR Reveals Simple Infection and Coinfection Episodes Increasing Risk for Graft Rejection in Solid Organ Transplantation.}, journal = {Viruses}, volume = {10}, number = {12}, pages = {}, doi = {10.3390/v10120730}, pmid = {30572622}, issn = {1999-4915}, support = {261307//Consejo Nacional de Ciencia y Tecnología/ ; HIM-2016-021//Fondo de Apoyo a la Investigación Hospital Infantil de México Federico Gómez/ ; }, abstract = {Herpesviruses are common components of the human microbiome that become clinically relevant when a competent immunosurveillance is compromised, such as in transplantation. Members of the beta and gamma subfamilies are associated with a wide diversity of pathologies, including end-organ disease and cancer. In this study, we developed a multiplex qPCR technique with high specificity, sensitivity, efficiency and predictability that allowed the simultaneous detection and quantification of beta and gamma human herpesviruses. The technique was tested in a cohort of 34 kidney- or liver-transplanted pediatric patients followed up for up to 12 months post-transplant. Viral load was determined in 495 leukocyte-plasma paired samples collected bi-weekly or monthly. Human herpesvirus (HHV) 7 was the herpesvirus most frequently found in positive samples (39%), followed by Epstein-Barr virus (EBV) (20%). Also, EBV and HHV7 were present in the majority of coinfection episodes (62%). The share of positive samples exclusively detected either in leukocytes or plasma was 85%, suggesting that these herpesviruses tended to take a latent or lytic path in an exclusive manner. Infection by human cytomegalovirus (HCMV) and HHV6, as well as coinfection by EBV/HHV7 and EBV/HHV6/HHV7, were associated with graft rejection (RR = 40.33 (p = 0.0013), 5.60 (p = 0.03), 5.60 (p = 0.03) and 17.64 (p = 0.0003), respectively). The routine monitoring of beta and gamma herpesviruses should be mandatory in transplant centers to implement preventive strategies.}, } @article {pmid30564562, year = {2018}, author = {Proal, A and Marshall, T}, title = {Myalgic Encephalomyelitis/Chronic Fatigue Syndrome in the Era of the Human Microbiome: Persistent Pathogens Drive Chronic Symptoms by Interfering With Host Metabolism, Gene Expression, and Immunity.}, journal = {Frontiers in pediatrics}, volume = {6}, number = {}, pages = {373}, doi = {10.3389/fped.2018.00373}, pmid = {30564562}, issn = {2296-2360}, abstract = {The illness ME/CFS has been repeatedly tied to infectious agents such as Epstein Barr Virus. Expanding research on the human microbiome now allows ME/CFS-associated pathogens to be studied as interacting members of human microbiome communities. Humans harbor these vast ecosystems of bacteria, viruses and fungi in nearly all tissue and blood. Most well-studied inflammatory conditions are tied to dysbiosis or imbalance of the human microbiome. While gut microbiome dysbiosis has been identified in ME/CFS, microbes and viruses outside the gut can also contribute to the illness. Pathobionts, and their associated proteins/metabolites, often control human metabolism and gene expression in a manner that pushes the body toward a state of illness. Intracellular pathogens, including many associated with ME/CFS, drive microbiome dysbiosis by directly interfering with human transcription, translation, and DNA repair processes. Molecular mimicry between host and pathogen proteins/metabolites further complicates this interference. Other human pathogens disable mitochondria or dysregulate host nervous system signaling. Antibodies and/or clonal T cells identified in patients with ME/CFS are likely activated in response to these persistent microbiome pathogens. Different human pathogens have evolved similar survival mechanisms to disable the host immune response and host metabolic pathways. The metabolic dysfunction driven by these organisms can result in similar clusters of inflammatory symptoms. ME/CFS may be driven by this pathogen-induced dysfunction, with the nature of dysbiosis and symptom presentation varying based on a patient's unique infectious and environmental history. Under such conditions, patients would benefit from treatments that support the human immune system in an effort to reverse the infectious disease process.}, } @article {pmid30559213, year = {2018}, author = {Tedijanto, C and Olesen, SW and Grad, YH and Lipsitch, M}, title = {Estimating the proportion of bystander selection for antibiotic resistance among potentially pathogenic bacterial flora.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {}, number = {}, pages = {}, doi = {10.1073/pnas.1810840115}, pmid = {30559213}, issn = {1091-6490}, abstract = {Bystander selection-the selective pressure for resistance exerted by antibiotics on microbes that are not the target pathogen of treatment-is critical to understanding the total impact of broad-spectrum antibiotic use on pathogenic bacterial species that are often carried asymptomatically. However, to our knowledge, this effect has never been quantified. We quantify bystander selection for resistance for a range of clinically relevant antibiotic-species pairs as the proportion of all antibiotic exposures received by a species for conditions in which that species was not the causative pathogen ("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.}, } @article {pmid30559176, year = {2018}, author = {Relman, DA and Lipsitch, M}, title = {Microbiome as a tool and a target in the effort to address antimicrobial resistance.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {}, number = {}, pages = {}, doi = {10.1073/pnas.1717163115}, pmid = {30559176}, issn = {1091-6490}, abstract = {Reciprocal, intimate relationships between the human microbiome and the host immune system are shaped by past microbial encounters and prepare the host for future ones. Antibiotics and other antimicrobials leave their mark on both the microbiome and host immunity. Antimicrobials alter the structure of the microbiota, expand the host-specific pool of antimicrobial-resistance genes and organisms, degrade the protective effects of the microbiota against invasion by pathogens, and may impair vaccine efficacy. Through these effects on the microbiome they may affect immune responses. Vaccines that exert protective or therapeutic effects against pathogens may reduce the use of antimicrobials, the development and spread of antimicrobial resistance, and the harmful impacts of these drugs on the microbiome. Other strategies involving manipulation of the microbiome to deplete antibiotic-resistant organisms or to enhance immune responses to vaccines may prove valuable in addressing antimicrobial resistance as well. This article describes the intersections of immunity, microbiome and antimicrobial exposure, and the use of vaccines and other alternative strategies for the control and management of antimicrobial resistance.}, } @article {pmid30551740, year = {2018}, author = {Romani, L and Pane, S and Severini, C and Menegon, M and Foglietta, G and Bernardi, S and Tchidjou, HK and Onetti Muda, A and Palma, P and Putignani, L}, title = {Challenging diagnosis of congenital malaria in non-endemic areas.}, journal = {Malaria journal}, volume = {17}, number = {1}, pages = {470}, doi = {10.1186/s12936-018-2614-9}, pmid = {30551740}, issn = {1475-2875}, support = {RC2018//Bambino Gesù Children's Hospital/ ; }, abstract = {BACKGROUND: Congenital malaria is usually defined as the detection of asexual forms of Plasmodium spp. in a blood sample of a neonate during perinatal age if there is no possibility of postpartum infection by a mosquito bite. The incidence of congenital malaria is highly variable and seems related to several factors, such as different diagnostic methods for Plasmodium spp. detection, and area in which the epidemiologic analyses are performed. In non-endemic countries, cases of congenital malaria are rare. Hereby, a case of a congenital malaria in an HIV exposed child is reported.

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.}, } @article {pmid30544936, year = {2018}, author = {D'Argenio, V}, title = {The Prenatal Microbiome: A New Player for Human Health.}, journal = {High-throughput}, volume = {7}, number = {4}, pages = {}, doi = {10.3390/ht7040038}, pmid = {30544936}, issn = {2571-5135}, abstract = {The last few years have featured an increasing interest in the study of the human microbiome and its correlations with health status. Indeed, technological advances have allowed the study of microbial communities to reach a previously unthinkable sensitivity, showing the presence of microbes also in environments usually considered as sterile. In this scenario, microbial communities have been described in the amniotic fluid, the umbilical blood cord, and the placenta, denying a dogma of reproductive medicine that considers the uterus like a sterile womb. This prenatal microbiome may play a role not only in fetal development but also in the predisposition to diseases that may develop later in life, and also in adulthood. Thus, the aim of this review is to report the current knowledge regarding the prenatal microbiome composition, its association with pathological processes, and the future perspectives regarding its manipulation for healthy status promotion and maintenance.}, } @article {pmid30524957, year = {2018}, author = {Yang, J and Mu, X and Wang, Y and Zhu, D and Zhang, J and Liang, C and Chen, B and Wang, J and Zhao, C and Zuo, Z and Heng, X and Zhang, C and Zhang, L}, title = {Dysbiosis of the Salivary Microbiome Is Associated With Non-smoking Female Lung Cancer and Correlated With Immunocytochemistry Markers.}, journal = {Frontiers in oncology}, volume = {8}, number = {}, pages = {520}, doi = {10.3389/fonc.2018.00520}, pmid = {30524957}, issn = {2234-943X}, abstract = {Background: Association between oral bacteria and increased risk of lung cancer have been reported in several previous studies, however, the potential association between salivary microbiome and lung cancer in non-smoking women have not been evaluated. There is also no report on the relationship between immunocytochemistry markers and salivary microbiota. Method: In this study, we assessed the salivary microbiome of 75 non-smoking female lung cancer patients and 172 matched healthy individuals using 16S rRNA gene amplicon sequencing. We also calculated the Spearman's rank correlation coefficient between salivary microbiota and three immunohistochemical markers (TTF-1, Napsin A and CK7). Result: We analyzed the salivary microbiota of 247 subjects and found that non-smoking female lung cancer patients exhibited oral microbial dysbiosis. There was significantly lower microbial diversity and richness in lung cancer patients when compared to the control group (Shannon index, P < 0.01; Ace index, P < 0.0001). Based on the analysis of similarities, the composition of the microbiota in lung cancer patients also differed from that of the control group (r = 0.454, P < 0.001, unweighted UniFrac; r = 0.113, P < 0.01, weighted UniFrac). The bacterial genera Sphingomonas (P < 0.05) and Blastomonas (P < 0.0001) were relatively higher in non-smoking female lung cancer patients, whereas Acinetobacter (P < 0.001) and Streptococcus (P < 0.01) were higher in controls. Based on Spearman's correlation analysis, a significantly positive correlation can be observed between CK7 and Enterobacteriaceae (r = 0.223, P < 0.05). At the same time, Napsin A was positively associated with genera Blastomonas (r = 0.251, P < 0.05). TTF-1 exhibited a significantly positive correlation with Enterobacteriaceae (r = 0.262, P < 0.05). Functional analysis from inferred metagenomes indicated that oral microbiome in non-smoking female lung cancer patients were related to cancer pathways, p53 signaling pathway, apoptosis and tuberculosis. Conclusions: The study identified distinct salivary microbiome profiles in non-smoking female lung cancer patients, revealed potential correlations between salivary microbiome and immunocytochemistry markers used in clinical diagnostics, and provided proof that salivary microbiota can be an informative source for discovering non-invasive lung cancer biomarkers.}, } @article {pmid30534599, year = {2018}, author = {Escapa, IF and Chen, T and Huang, Y and Gajare, P and Dewhirst, FE and Lemon, KP}, title = {New Insights into Human Nostril Microbiome from the Expanded Human Oral Microbiome Database (eHOMD): a Resource for the Microbiome of the Human Aerodigestive Tract.}, journal = {mSystems}, volume = {3}, number = {6}, pages = {}, doi = {10.1128/mSystems.00187-18}, pmid = {30534599}, issn = {2379-5077}, abstract = {The expanded Human Oral Microbiome Database (eHOMD) is a comprehensive microbiome database for sites along the human aerodigestive tract that revealed new insights into the nostril microbiome. The eHOMD provides well-curated 16S rRNA gene reference sequences linked to available genomes and enables assignment of species-level taxonomy to most next-generation sequences derived from diverse aerodigestive tract sites, including the nasal passages, sinuses, throat, esophagus, and mouth. Using minimum entropy decomposition coupled with the RDP Classifier and our eHOMD V1-V3 training set, we reanalyzed 16S rRNA V1-V3 sequences from the nostrils of 210 Human Microbiome Project participants at the species level, revealing four key insights. First, we discovered that Lawsonella clevelandensis, a recently named bacterium, and Neisseriaceae [G-1] HMT-174, a previously unrecognized bacterium, are common in adult nostrils. Second, just 19 species accounted for 90% of the total sequences from all participants. Third, 1 of these 19 species belonged to a currently uncultivated genus. Fourth, for 94% of the participants, 2 to 10 species constituted 90% of their sequences, indicating that the nostril microbiome may be represented by limited consortia. These insights highlight the strengths of the nostril microbiome as a model system for studying interspecies interactions and microbiome function. Also, in this cohort, three common nasal species (Dolosigranulum pigrum and two Corynebacterium species) showed positive differential abundance when the pathobiont Staphylococcus aureus was absent, generating hypotheses regarding colonization resistance. By facilitating species-level taxonomic assignment to microbes from the human aerodigestive tract, the eHOMD is a vital resource enhancing clinical relevance of microbiome studies. IMPORTANCE The eHOMD (http://www.ehomd.org) is a valuable resource for researchers, from basic to clinical, who study the microbiomes and the individual microbes in body sites in the human aerodigestive tract, which includes the nasal passages, sinuses, throat, esophagus, and mouth, and the lower respiratory tract, in health and disease. The eHOMD is an actively curated, web-based, open-access resource. eHOMD provides the following: (i) species-level taxonomy based on grouping 16S rRNA gene sequences at 98.5% identity, (ii) a systematic naming scheme for unnamed and/or uncultivated microbial taxa, (iii) reference genomes to facilitate metagenomic, metatranscriptomic, and proteomic studies and (iv) convenient cross-links to other databases (e.g., PubMed and Entrez). By facilitating the assignment of species names to sequences, the eHOMD is a vital resource for enhancing the clinical relevance of 16S rRNA gene-based microbiome studies, as well as metagenomic studies.}, } @article {pmid30532649, year = {2018}, author = {Lim, MY and Cho, Y and Rho, M}, title = {Diverse Distribution of Resistomes in the Human and Environmental Microbiomes.}, journal = {Current genomics}, volume = {19}, number = {8}, pages = {701-711}, doi = {10.2174/1389202919666180911130845}, pmid = {30532649}, issn = {1389-2029}, abstract = {The routine therapeutic use of antibiotics has caused resistance genes to be disseminated across microbial populations. In particular, bacterial strains having antibiotic resistance genes are frequently observed in the human microbiome. Moreover, multidrug-resistant pathogens are now widely spread, threatening public health. Such genes are transferred and spread among bacteria even in different environments. Advances in high throughput sequencing technology and computational algorithms have accelerated investigation into antibiotic resistance genes of bacteria. Such studies have revealed that the antibiotic resistance genes are located close to the mobility-associated genes, which promotes their dissemination. An increasing level of information on genomic sequences of resistome should expedite research on drug-resistance in our body and environment, thereby contributing to the development of public health policy. In this review, the high prevalence of antibiotic resistance genes and their exchange in the human and environmental microbiome is discussed with respect to the genomic contents. The relationships among diverse resistomes, related bacterial species, and the antibiotics are reviewed. In addition, recent advances in bioinformatics approaches to investigate such relationships are discussed.}, } @article {pmid30530088, year = {2018}, author = {Ben, Y and Fu, C and Hu, M and Liu, L and Wong, MH and Zheng, C}, title = {Human health risk assessment of antibiotic resistance associated with antibiotic residues in the environment: A review.}, journal = {Environmental research}, volume = {169}, number = {}, pages = {483-493}, doi = {10.1016/j.envres.2018.11.040}, pmid = {30530088}, issn = {1096-0953}, abstract = {The extensive use of antibiotics leading to the rapid spread of antibiotic resistance poses high health risks to humans, but to date there is still lack of a quantitative model to properly assess the risks. Concerns over the health risk of antibiotic residues in the environment are mainly (1) the potential hazard of ingested antibiotic residues in the environment altering the human microbiome and promoting emergence and selection for bacteria resistance inhabiting the human body, and (2) the potential hazard of creating a selection pressure on environmental microbiome and leading to reservoirs of antibiotic resistance in the environment. We provide a holistic view of health risk assessment of antibiotic resistance associated with antibiotic residues in the environment in contrast with that of the antibiotic resistant bacteria and discuss the main knowledge gaps and the future research that should be prioritized to achieve the quantitative risk assessment. We examined and summarized the available data and information on the four core elements of antibiotic resistance associated with antibiotic residues in the environment: hazard identification, exposure assessment, dose-response assessment, and risk characterization. The data required to characterize the risks of antibiotic residues in the environment is severely limited. The main future research needs have been identified to enable better assessments of antibiotic resistance associated with antibiotic residues in the environment: (1) establishment of a standardized monitoring guide of antibiotic residues and antibiotic resistance in the environment, (2) derivation of the relationship between antibiotic levels and pathogenic antibiotic-resistance development in different settings, and (3) establishment of the dose-response relationship between pathogenic antibiotic resistant bacteria and various infection diseases. After identification of key risk determinant parameters, we propose a conceptual framework of human health risk assessments of antibiotic residues in the environment. CAPSULE: A holistic view of human health risk assessment of antibiotic residues in the environment was provided.}, } @article {pmid30529020, year = {2018}, author = {Robertson, RC and Manges, AR and Finlay, BB and Prendergast, AJ}, title = {The Human Microbiome and Child Growth - First 1000 Days and Beyond.}, journal = {Trends in microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.tim.2018.09.008}, pmid = {30529020}, issn = {1878-4380}, abstract = {The assembly of microbial communities within the gastrointestinal tract during early life plays a critical role in immune, endocrine, metabolic, and other host developmental pathways. Environmental insults during this period, such as food insecurity and infections, can disrupt this optimal microbial succession, which may contribute to lifelong and intergenerational deficits in growth and development. Here, we review the human microbiome in the first 1000 days - referring to the period from conception to 2 years of age - and using a developmental model, we examine the role of early microbial succession in growth and development. We propose that an 'undernourished' microbiome is intergenerational, thereby perpetuating growth impairments into successive generations. We also identify and discuss the intertwining host-microbe-environment interactions occurring prenatally and during early infancy, which may impair the trajectories of healthy growth and development, and explore their potential as novel microbial targets for intervention.}, } @article {pmid30526758, year = {2018}, author = {Blaser, MJ}, title = {Our missing microbes: Short-term antibiotic courses have long-term consequences.}, journal = {Cleveland Clinic journal of medicine}, volume = {85}, number = {12}, pages = {928-930}, doi = {10.3949/ccjm.85gr.18005}, pmid = {30526758}, issn = {1939-2869}, } @article {pmid30521647, year = {2018}, author = {Jeżewska-Frąckowiak, J and Seroczyńska, K and Banaszczyk, J and Woźniak, D and Żylicz-Stachula, A and Skowron, PM}, title = {The promises and risks of probiotic Bacillus species.}, journal = {Acta biochimica Polonica}, volume = {}, number = {}, pages = {}, doi = {10.18388/abp.2018_2652}, pmid = {30521647}, issn = {1734-154X}, abstract = {Supplementing the human microbiome with probiotic microorganisms is a proposed solution for civilization syndromes such as dysbiosis and gastrointestinal tract (GIT) disorders. Bimodal probiotic strains of the Bacillus genus constitute the microbiota of the human environment, and are typically found in soil, water, a number of non-dairy fermented foods, as well as in human and animal GIT. Probiotic Bacillus sp. are Gram positive rods, with the ability of sporulation to survive environmental stress and preparation conditions. In vitro models of the human stomach and human studies with probiotic Bacillus reveal the mechanisms of its life cycle and sporulation. The Bacillus sp. probiotic biofilm introduces biochemical effects such as antimicrobial and enzymatic activity, thus contributing to protection from GIT and other infections. Despite the beneficial activity of Bacillus strains belonging to the safety group 1, a number of strains can pose a substantial health risk, carrying genes for various toxins or antibiotic resistance. Commercially available Bacillus probiotic preparations include strains from the subtilis and other closely related phylogenetic clades. Those intended for oral administration in humans, often encapsulated with appropriate supporting materials, still tend to be mislabeled or poorly characterized. Bacillus sp. MALDI-TOF analysis, combined with sequencing of characteristic 16S rRNA or enzyme coding genes, may provide accurate identification. A promising future application of the probiotic Bacillus sp. might be the microflora biocontrol in the human body and the closest human environment. Environmental probiotic Bacillus species display the potential to support human microflora, however controversies regarding the safety of certain strains is a key factor in their still limited application.}, } @article {pmid30521551, year = {2018}, author = {Vernocchi, P and Del Chierico, F and Russo, A and Majo, F and Rossitto, M and Valerio, M and Casadei, L and La Storia, A and De Filippis, F and Rizzo, C and Manetti, C and Paci, P and Ercolini, D and Marini, F and Fiscarelli, EV and Dallapiccola, B and Lucidi, V and Miccheli, A and Putignani, L}, title = {Gut microbiota signatures in cystic fibrosis: Loss of host CFTR function drives the microbiota enterophenotype.}, journal = {PloS one}, volume = {13}, number = {12}, pages = {e0208171}, doi = {10.1371/journal.pone.0208171}, pmid = {30521551}, issn = {1932-6203}, abstract = {BACKGROUND: Cystic fibrosis (CF) is a disorder affecting the respiratory, digestive, reproductive systems and sweat glands. This lethal hereditary disease has known or suspected links to the dysbiosis gut microbiota. High-throughput meta-omics-based approaches may assist in unveiling this complex network of symbiosis modifications.

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.}, } @article {pmid30519775, year = {2018}, author = {Slobodin, G and Rosner, I and Kessel, A}, title = {Dendritic cells in the pathogenesis of ankylosing spondylitis and axial spondyloarthritis.}, journal = {Clinical rheumatology}, volume = {}, number = {}, pages = {}, doi = {10.1007/s10067-018-4388-4}, pmid = {30519775}, issn = {1434-9949}, abstract = {The interaction of dendritic cells (DCs) with the human microbiome, with distorted handling of the microbiota or its products via the direct effect of HLA B27, probably represents the initial element in the chain of events leading to the development of clinical axial spondyloarthritis. The mechanism of disease extension onto the skeleton and other tissues involved, such as uvea, may also involve migratory DCs. Finally, the role of DCs in the initiation of the inflammatory tissue response with activation of the IL-17 axis has been demonstrated. Further, some initial data suggests the possible connection of DCs with disease-related new bone formation.}, } @article {pmid30507717, year = {2018}, author = {Lai, PS and Christiani, DC}, title = {Impact of occupational exposure on human microbiota.}, journal = {Current opinion in allergy and clinical immunology}, volume = {}, number = {}, pages = {}, doi = {10.1097/ACI.0000000000000502}, pmid = {30507717}, issn = {1473-6322}, abstract = {PURPOSE OF REVIEW: Recent evidence suggests that environmental exposures change the adult human microbiome. Here, we review recent evidence on the impact of the work microbiome and work-related chemical, metal and particulate exposures on the human microbiome.

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.}, } @article {pmid30514510, year = {2018}, author = {O'Toole, RF and Gautam, SS}, title = {The host microbiome and impact of tuberculosis chemotherapy.}, journal = {Tuberculosis (Edinburgh, Scotland)}, volume = {113}, number = {}, pages = {26-29}, doi = {10.1016/j.tube.2018.08.015}, pmid = {30514510}, issn = {1873-281X}, abstract = {The treatment of Mycobacterium tuberculosis infection is often viewed in isolation from other human microbial symbionts. Understandably, the clinical priority is eliminating active or latent tuberculosis (TB) in patients. With the increasing resolution of molecular biology technologies, it is becoming apparent that antibiotic treatment can perturb the homeostasis of the host microbiome. For example, dysbiosis of the gut microbiota has been associated with an increased risk of the development of asthma, obesity and diabetes. Therefore, fundamental questions include: Does TB chemotherapy cause disruption of the human microbiome and adverse effects in patients; and are there signature taxa of dysbiosis following TB treatment. In this review, we examine recent research on the detection of changes in the microbiome during antibiotic administration and discuss specific findings that relate to the impact of anti-tubercular chemotherapy.}, } @article {pmid30510919, year = {2018}, author = {Brenner, LA and Hoisington, AJ and Stearns-Yoder, KA and Stamper, CE and Heinze, JD and Postolache, TT and Hadidi, DA and Hoffmire, CA and Stanislawski, MA and Lowry, CA}, title = {Military-Related Exposures, Social Determinants of Health, and Dysbiosis: The United States-Veteran Microbiome Project (US-VMP).}, journal = {Frontiers in cellular and infection microbiology}, volume = {8}, number = {}, pages = {400}, doi = {10.3389/fcimb.2018.00400}, pmid = {30510919}, issn = {2235-2988}, abstract = {Significant effort has been put forth to increase understanding regarding the role of the human microbiome in health- and disease-related processes. In turn, the United States (US) Veteran Microbiome Project (US-VMP) was conceptualized as a means by which to serially collect microbiome and health-related data from those seeking care within the Veterans Health Administration (VHA). In this manuscript, exposures related to military experiences, as well as conditions and health-related factors among patients seen in VHA clinical settings are discussed in relation to common psychological and physical outcomes. Upon enrollment in the study, Veterans complete psychometrically sound (i.e., reliable and valid) measures regarding their past and current medical history. Participants also provide skin, oral, and gut microbiome samples, and permission to track their health status via the VHA electronic medical record. To date, data collection efforts have been cross-diagnostic. Within this manuscript, we describe current data collection practices and procedures, as well as highlight demographic, military, and psychiatric characteristics of the first 188 Veterans enrolled in the study. Based on these findings, we assert that this cohort is unique as compared to those enrolled in recent large-scale studies of the microbiome. To increase understanding regarding disease and health among diverse cohorts, efforts such as the US-VMP are vital. Ongoing barriers and facilitators to data collection are discussed, as well as future research directions, with an emphasis on the importance of shifting current thinking regarding the microbiome from a focus on normalcy and dysbiosis to health promotion and disease prevention.}, } @article {pmid30510497, year = {2018}, author = {Mathias, M}, title = {Autointoxication and historical precursors of the microbiome-gut-brain axis.}, journal = {Microbial ecology in health and disease}, volume = {29}, number = {2}, pages = {1548249}, doi = {10.1080/16512235.2018.1548249}, pmid = {30510497}, issn = {0891-060X}, abstract = {This article focuses on autointoxication, a discredited medical theory from the late nineteenth century that provides important points of reflection for today's research on the role of microbes in the human gut for mental health. It considers how the theory of autointoxication, which came into great prominence amongst physicians and the general public worldwide, fell from grace by the middle of the twentieth century, and briefly asks why studies of the human microbiome are now back in vogue. It departs from earlier articles on the topic firstly by arguing that autointoxication theory was especially prevalent in France, and secondly by focusing on the application of this theory to mental health. Bringing to light medical treatises and theses from this period which have so far remained unexamined, it shows that examining the development and reception of medical theories form the past can help us today in understanding both the pitfalls and promise of research in this area.}, } @article {pmid30487377, year = {2018}, author = {Ando, H}, title = {[Creation of synthetic bacterial viruses].}, journal = {Nihon saikingaku zasshi. Japanese journal of bacteriology}, volume = {73}, number = {4}, pages = {201-210}, doi = {10.3412/jsb.73.201}, pmid = {30487377}, issn = {1882-4110}, abstract = {Bacteria are closely related with human health and diseases. For example, the emergence of drug-resistant bacteria is a serious problem in the world. Studying the human microbiome shows its important role for our health. But we have very limited tools to edit bacterial population. Antibiotics are generally broad-spectrum and unable to kill only bad bacteria. The natural enemies of bacteria, called bacteriophage (phage), have highly specific host range, and thus promising candidates for targeted bacterial population editing. However, isolation and characterization of natural phages can be a time-, labor- and cost-intensive way. Also, developing phage-based therapeutics and diagnostics is limited by the difficulty of engineering phages. Here, I describe a phage genome-engineering platform and synthetic phages with tunable host ranges to overcome these challenges.}, } @article {pmid30485738, year = {2018}, author = {McCord, B and Gauthier, Q and Cho, S and Roig, M and Gibson-Daw, G and Young, B and Taglia, F and Zapico, SC and Mariot, RF and Lee, SB and Duncan, G}, title = {Forensic DNA Analysis.}, journal = {Analytical chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.analchem.8b05318}, pmid = {30485738}, issn = {1520-6882}, abstract = {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.}, } @article {pmid30482830, year = {2018}, author = {Espinoza, JL and Harkins, DM and Torralba, M and Gomez, A and Highlander, SK and Jones, MB and Leong, P and Saffery, R and Bockmann, M and Kuelbs, C and Inman, JM and Hughes, T and Craig, JM and Nelson, KE and Dupont, CL}, title = {Supragingival Plaque Microbiome Ecology and Functional Potential in the Context of Health and Disease.}, journal = {mBio}, volume = {9}, number = {6}, pages = {}, doi = {10.1128/mBio.01631-18}, pmid = {30482830}, issn = {2150-7511}, abstract = {To address the question of how microbial diversity and function in the oral cavities of children relates to caries diagnosis, we surveyed the supragingival plaque biofilm microbiome in 44 juvenile twin pairs. Using shotgun sequencing, we constructed a genome encyclopedia describing the core supragingival plaque microbiome. Caries phenotypes contained statistically significant enrichments in specific genome abundances and distinct community composition profiles, including strain-level changes. Metabolic pathways that are statistically associated with caries include several sugar-associated phosphotransferase systems, antimicrobial resistance, and metal transport. Numerous closely related previously uncharacterized microbes had substantial variation in central metabolism, including the loss of biosynthetic pathways resulting in auxotrophy, changing the ecological role. We also describe the first complete Gracilibacteria genomes from the human microbiome. Caries is a microbial community metabolic disorder that cannot be described by a single etiology, and our results provide the information needed for next-generation diagnostic tools and therapeutics for caries.IMPORTANCE Oral health has substantial economic importance, with over $100 billion spent on dental care in the United States annually. The microbiome plays a critical role in oral health, yet remains poorly classified. To address the question of how microbial diversity and function in the oral cavities of children relate to caries diagnosis, we surveyed the supragingival plaque biofilm microbiome in 44 juvenile twin pairs. Using shotgun sequencing, we constructed a genome encyclopedia describing the core supragingival plaque microbiome. This unveiled several new previously uncharacterized but ubiquitous microbial lineages in the oral microbiome. Caries is a microbial community metabolic disorder that cannot be described by a single etiology, and our results provide the information needed for next-generation diagnostic tools and therapeutics for caries.}, } @article {pmid30481125, year = {2018}, author = {Kim, JW and Lee, JS and Kim, JH and Jeong, JW and Lee, DH and Nam, S}, title = {Comparison of Microbiota Variation in Korean Healthy Adolescents with Adults Suggests Notable Maturity Differences.}, journal = {Omics : a journal of integrative biology}, volume = {}, number = {}, pages = {}, doi = {10.1089/omi.2018.0146}, pmid = {30481125}, issn = {1557-8100}, abstract = {Comparative studies of microbiome variation in world populations and different developmental stages of organisms are essential to decipher the linkages among microbiome, health, and disease. Notably, the gut microbiota are believed to mature in early life. In this context, we compared the gut microbiota diversity in Korean adolescent healthy samples (KAHSs) to healthy Korean adults (HKAs) as well as the Human Microbiome Project healthy samples (HMPHSs), the latter being one of the largest adult cohorts, based on organismal composition, alpha- and beta-diversities, function/pathway prediction analysis, and co-occurrence networks. We found that the gut microbiota compositions, including the ratios of firmicutes to bacteroidetes, between KAHSs and HMPHSs were different, and the diversities of KAHSs were less than those of HMPHSs. The predicted functions, for example, secondary bile acid synthesis and insulin signaling of KAHSs and HMPHSs, were also significantly different. Genus-level networks showed that co-occurrences among different taxa more frequently happened in HMPHSs than in KAHSs. Even though both KAHSs and HMPHSs represent healthy microbiomes, comparisons showed substantial differences, likely implicating different diets, environments, and demographics. Interestingly, we observed lower microbial diversities and less frequent co-occurrences among different taxa in KAHSs than adult HMPHSs and HKAs. These new findings collectively suggest that the adolescent gut microbiota in the present Korean sample did not reach the extent of maturity of adult microbiota diversity. In all, further population studies of microbiome variation across geographies and developmental stages are warranted, and should usefully inform future diagnostics and therapeutics innovation targeting the microbiome.}, } @article {pmid30477563, year = {2018}, author = {Sinha, R and Ahsan, H and Blaser, M and Caporaso, JG and Carmical, JR and Chan, AT and Fodor, A and Gail, MH and Harris, CC and Helzlsouer, K and Huttenhower, C and Knight, R and Kong, HH and Lai, GY and Hutchinson, DLS and Le Marchand, L and Li, H and Orlich, MJ and Shi, J and Truelove, A and Verma, M and Vogtmann, E and White, O and Willett, W and Zheng, W and Mahabir, S and Abnet, C}, title = {Next steps in studying the human microbiome and health in prospective studies, Bethesda, MD, May 16-17, 2017.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {210}, doi = {10.1186/s40168-018-0596-z}, pmid = {30477563}, issn = {2049-2618}, abstract = {The National Cancer Institute (NCI) sponsored a 2-day workshop, "Next Steps in Studying the Human Microbiome and Health in Prospective Studies," in Bethesda, Maryland, May 16-17, 2017. The workshop brought together researchers in the field to discuss the challenges of conducting microbiome studies, including study design, collection and processing of samples, bioinformatics and statistical methods, publishing results, and ensuring reproducibility of published results. The presenters emphasized the great potential of microbiome research in understanding the etiology of cancer. This report summarizes the workshop and presents practical suggestions for conducting microbiome studies, from workshop presenters, moderators, and participants.}, } @article {pmid30477107, year = {2018}, author = {Cristofori, F and Indrio, F and Miniello, VL and De Angelis, M and Francavilla, R}, title = {Probiotics in Celiac Disease.}, journal = {Nutrients}, volume = {10}, number = {12}, pages = {}, doi = {10.3390/nu10121824}, pmid = {30477107}, issn = {2072-6643}, abstract = {Recently, the interest in the human microbiome and its interplay with the host has exploded and provided new insights on its role in conferring host protection and regulating host physiology, including the correct development of immunity. However, in the presence of microbial imbalance and particular genetic settings, the microbiome may contribute to the dysfunction of host metabolism and physiology, leading to pathogenesis and/or the progression of several diseases. Celiac disease (CD) is a chronic autoimmune enteropathy triggered by dietary gluten exposure in genetically predisposed individuals. Despite ascertaining that gluten is the trigger in CD, evidence has indicated that intestinal microbiota is somehow involved in the pathogenesis, progression, and clinical presentation of CD. Indeed, several studies have reported imbalances in the intestinal microbiota of patients with CD that are mainly characterized by an increased abundance of Bacteroides spp. and a decrease in Bifidobacterium spp. The evidence that some of these microbial imbalances still persist in spite of a strict gluten-free diet and that celiac patients suffering from persistent gastrointestinal symptoms have a desert gut microbiota composition further support its close link with CD. All of this evidence gives rise to the hypothesis that probiotics might play a role in this condition. In this review, we describe the recent scientific evidences linking the gut microbiota in CD, starting from the possible role of microbes in CD pathogenesis, the attempt to define a microbial signature of disease, the effect of a gluten-free diet and host genetic assets regarding microbial composition to end in the exploration of the proof of concept of probiotic use in animal models to the most recent clinical application of selected probiotic strains.}, } @article {pmid30474490, year = {2018}, author = {Jonsson, V and Österlund, T and Nerman, O and Kristiansson, E}, title = {Modelling of zero-inflation improves inference of metagenomic gene count data.}, journal = {Statistical methods in medical research}, volume = {}, number = {}, pages = {962280218811354}, doi = {10.1177/0962280218811354}, pmid = {30474490}, issn = {1477-0334}, abstract = {Metagenomics enables the study of gene abundances in complex mixtures of microorganisms and has become a standard methodology for the analysis of the human microbiome. However, gene abundance data is inherently noisy and contains high levels of biological and technical variability as well as an excess of zeros due to non-detected genes. This makes the statistical analysis challenging. In this study, we present a new hierarchical Bayesian model for inference of metagenomic gene abundance data. The model uses a zero-inflated overdispersed Poisson distribution which is able to simultaneously capture the high gene-specific variability as well as zero observations in the data. By analysis of three comprehensive datasets, we show that zero-inflation is common in metagenomic data from the human gut and, if not correctly modelled, it can lead to substantial reductions in statistical power. We also show, by using resampled metagenomic data, that our model has, compared to other methods, a higher and more stable performance for detecting differentially abundant genes. We conclude that proper modelling of the gene-specific variability, including the excess of zeros, is necessary to accurately describe gene abundances in metagenomic data. The proposed model will thus pave the way for new biological insights into the structure of microbial communities.}, } @article {pmid30466159, year = {2018}, author = {Mendez, R and Banerjee, S and Bhattacharya, SK and Banerjee, S}, title = {Lung inflammation and disease: A perspective on microbial homeostasis and metabolism.}, journal = {IUBMB life}, volume = {}, number = {}, pages = {}, doi = {10.1002/iub.1969}, pmid = {30466159}, issn = {1521-6551}, support = {EY14801//National Eye Institute/ ; R21HL125021//National Heart, Lung, and Blood Institute/ ; }, abstract = {It is now well appreciated that the human microbiome plays a significant role in a number of processes in the body, significantly affecting its metabolic, inflammatory, and immune homeostasis. Recent research has revealed that almost every mucosal surface in the human body is associated with a resident commensal microbiome of its own. While the gut microbiome and its role in regulation of host metabolism along with its alteration in a disease state has been well studied, there is a lacuna in understanding the resident microbiota of other mucosal surfaces. Among these, the scientific information on the role of lung microbiota in pulmonary diseases is currently severely limited. Historically, lungs have been considered to be sterile and lung diseases have only been studied in the context of bacterial pathogenesis. Recently however, studies have revealed a resilient microbiome in the upper and lower respiratory tracts and there is increased evidence on its central role in respiratory diseases. Knowledge of lung microbiome and its metabolic fallout (local and systemic) is still in its nascent stages and attracting immense interest in recent times. In this review, we will provide a perspective on lung-associated metabolic disorders defined for lung diseases (e.g., chronic obstructive pulmonary disease, asthma, and respiratory depression due to infection) and correlate it with lung microbial perturbation. Such perturbations may be due to altered biochemical or metabolic stress as well. Finally, we will draw evidence from microbiome and classical microbiology literature to demonstrate how specific lung morbidities associate with specific metabolic characteristics of the disease, and with the role of microbiome in this context. © 2018 IUBMB Life, 1-14, 2018.}, } @article {pmid30466152, year = {2018}, author = {Beilsmith, K and Thoen, MPM and Brachi, B and Gloss, AD and Khan, MH and Bergelson, J}, title = {Genome-Wide Association studies on the phyllosphere microbiome: embracing complexity in host-microbe interactions.}, journal = {The Plant journal : for cell and molecular biology}, volume = {}, number = {}, pages = {}, doi = {10.1111/tpj.14170}, pmid = {30466152}, issn = {1365-313X}, abstract = {Environmental sequencing shows that plants harbor complex communities of microbes that vary across environments. However, many approaches for mapping plant genetic variation to microbe-related traits were developed in the relatively simple context of binary host-microbe interactions under controlled conditions. Recent advances in sequencing and statistics make genome-wide association studies (GWAS) an increasingly promising approach for identifying the plant genetic variation associated with microbes in a community context. This review discusses early efforts at GWAS of the plant phyllosphere microbiome and the outlook for future studies based on human microbiome GWAS. A workflow for GWAS of the phyllosphere microbiome is then presented, with particular attention to how perspectives on the mechanisms, evolution, and environmental dependence of plant-microbe interactions will influence the choice of traits to be mapped. This article is protected by copyright. All rights reserved.}, } @article {pmid30465353, year = {2018}, author = {Wang, H and Kang, D and Zhou, XD and Li, YQ}, title = {[Prevention of infectious diseases through microecology modulation techniques].}, journal = {Hua xi kou qiang yi xue za zhi = Huaxi kouqiang yixue zazhi = West China journal of stomatology}, volume = {36}, number = {5}, pages = {564-567}, doi = {10.7518/hxkq.2018.05.018}, pmid = {30465353}, issn = {1000-1182}, abstract = {The microbe is small in volume, but large in quantity and species. The symbiotic microbe, which is far more than human cells, code millions times of genes than human being. Somatic cells and these symbiotic microbe distributing in human body skin, respiratory tract, oral cavity and gastrointestinal tract, urinary tract and other parts form a complex ecosystem whose dynamic balance is highly related to body health. With the successful implementation of Human Microbiome Project, more attentions have been paid to the next generation microbiome technologies. New tools and methods for ecological regulation of human microbiome are emerging. The way we improve the world of human microbiology will be more convenient. This paper will make a review on the modulation techniques of human microbiome.}, } @article {pmid30460770, year = {2018}, author = {Barbara, G and Cremon, C and Azpiroz, F}, title = {Probiotics in irritable bowel syndrome: Where are we?.}, journal = {Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society}, volume = {30}, number = {12}, pages = {e13513}, doi = {10.1111/nmo.13513}, pmid = {30460770}, issn = {1365-2982}, support = {SAF 2016-76648-R//Italian Ministry of Education, University and Research, and the Spanish Ministry of Economy and Competitiveness/ ; //Instituto de Salud Carlos III/ ; //University of Bologna RFO/ ; //Fondazione del Monte di Bologna e Ravenna/ ; }, abstract = {We have only recently begun to understand how alterations of the intestinal microbial ecosystem lead to the disruption of host-microbial interactions and are associated with diseases, including functional gastrointestinal disorders such as irritable bowel syndrome (IBS). Although we are still far from understanding the human microbiome, gut microbiota is already a therapeutic target. Probiotics are live microorganisms that, when administered in adequate amounts, confer a health benefit to the host and may represent a therapeutic option for diseases characterized by dysbiosis such as IBS. Meta-analyses suggest that probiotics provide a therapeutic gain over placebo on global symptoms with a high safety profile in IBS patients. However, the mechanisms by which they provide benefit in IBS remain virtually unknown. In this issue of Neurogastroenterology and Motility, BIO-25, a multispecies probiotic, did not significantly modify the composition of the fecal microbiota, but interestingly, patients with specific basal features of the intestinal microbial ecosystem improved with treatment. Based on these data, it is tantalizing to speculate that microbiota composition serves as a predictor of the response to probiotic intervention. This mini-review addresses unresolved issues related to mechanisms through which probiotics may exert their beneficial effects, the biological, as well as clinical predictors of favorable outcomes in IBS and finally considers possible new directions for future studies.}, } @article {pmid30459400, year = {2018}, author = {Chen, B and Zhao, Y and Li, S and Yang, L and Wang, H and Wang, T and Bin Shi, and Gai, Z and Heng, X and Zhang, C and Yang, J and Zhang, L}, title = {Variations in oral microbiome profiles in rheumatoid arthritis and osteoarthritis with potential biomarkers for arthritis screening.}, journal = {Scientific reports}, volume = {8}, number = {1}, pages = {17126}, doi = {10.1038/s41598-018-35473-6}, pmid = {30459400}, issn = {2045-2322}, support = {No. 31471202//National Natural Science Foundation of China (National Science Foundation of China)/ ; }, abstract = {The key to arthritis management is early diagnosis and treatment to prevent further joint destruction and maximize functional ability. Osteoarthritis (OA) and rheumatoid arthritis (RA) are two common types of arthritis that the primary care provider must differentiate, in terms of diagnosis and treatment. Effective and non-invasive strategies for early detection and disease identification are sorely needed. Growing evidence suggests that RA has a correlation with oral microbiome and may be affected by its dynamic variations. There is already a study comparing oral microbiome in patients with RA and OA, however, it did not screen for potential biomarkers for arthritis. In this study, we assessed the oral microbiome in saliva samples from 110 RA patients, 67 OA patients and 155 healthy subjects, using 16S rRNA gene amplicon sequencing. The structure and differences in oral microbiome between RA, OA and healthy subjects were analyzed. Eight oral bacterial biomarkers were identified to differentiate RA from OA. This report provides proof of oral microbiota as an informative source for discovering non-invasive biomarkers for arthritis screening.}, } @article {pmid30452039, year = {2018}, author = {Rajakovich, LJ and Balskus, EP}, title = {Metabolic functions of the human gut microbiota: the role of metalloenzymes.}, journal = {Natural product reports}, volume = {}, number = {}, pages = {}, doi = {10.1039/c8np00074c}, pmid = {30452039}, issn = {1460-4752}, abstract = {Covering: up to the end of 2017The human body is composed of an equal number of human and microbial cells. While the microbial community inhabiting the human gastrointestinal tract plays an essential role in host health, these organisms have also been connected to various diseases. Yet, the gut microbial functions that modulate host biology are not well established. In this review, we describe metabolic functions of the human gut microbiota that involve metalloenzymes. These activities enable gut microbial colonization, mediate interactions with the host, and impact human health and disease. We highlight cases in which enzyme characterization has advanced our understanding of the gut microbiota and examples that illustrate the diverse ways in which metalloenzymes facilitate both essential and unique functions of this community. Finally, we analyze Human Microbiome Project sequencing datasets to assess the distribution of a prominent family of metalloenzymes in human-associated microbial communities, guiding future enzyme characterization efforts.}, } @article {pmid30449316, year = {2018}, author = {Guerin, E and Shkoporov, A and Stockdale, SR and Clooney, AG and Ryan, FJ and Sutton, TDS and Draper, LA and Gonzalez-Tortuero, E and Ross, RP and Hill, C}, title = {Biology and Taxonomy of crAss-like Bacteriophages, the Most Abundant Virus in the Human Gut.}, journal = {Cell host & microbe}, volume = {24}, number = {5}, pages = {653-664.e6}, doi = {10.1016/j.chom.2018.10.002}, pmid = {30449316}, issn = {1934-6069}, abstract = {CrAssphages represent the most abundant virus in the human gut microbiota, but the lack of available genome sequences for comparison has kept them enigmatic. Recently, sequence-based classification of distantly related crAss-like phages from multiple environments was reported, leading to a proposed familial-level taxonomic group. Here, we assembled the metagenomic sequencing reads from 702 human fecal virome/phageome samples and analyzed 99 complete circular crAss-like phage genomes and 150 contigs ≥70 kb. In silico comparative genomics and taxonomic analysis enabled a classification scheme of crAss-like phages from human fecal microbiomes into four candidate subfamilies composed of ten candidate genera. Laboratory analysis was performed on fecal samples from an individual harboring seven distinct crAss-like phages. We achieved crAss-like phage propagation in ex vivo human fecal fermentations and visualized short-tailed podoviruses by electron microscopy. Mass spectrometry of a crAss-like phage capsid protein could be linked to metagenomic sequencing data, confirming crAss-like phage structural annotations.}, } @article {pmid30443602, year = {2018}, author = {Hillmann, B and Al-Ghalith, GA and Shields-Cutler, RR and Zhu, Q and Gohl, DM and Beckman, KB and Knight, R and Knights, D}, title = {Evaluating the Information Content of Shallow Shotgun Metagenomics.}, journal = {mSystems}, volume = {3}, number = {6}, pages = {}, doi = {10.1128/mSystems.00069-18}, pmid = {30443602}, issn = {2379-5077}, abstract = {Although microbial communities are associated with human, environmental, plant, and animal health, there exists no cost-effective method for precisely characterizing species and genes in such communities. While deep whole-metagenome shotgun (WMS) sequencing provides high taxonomic and functional resolution, it is often prohibitively expensive for large-scale studies. The prevailing alternative, 16S rRNA gene amplicon (16S) sequencing, often does not resolve taxonomy past the genus level and provides only moderately accurate predictions of the functional profile; thus, there is currently no widely accepted approach to affordable, high-resolution, taxonomic, and functional microbiome analysis. To address this technology gap, we evaluated the information content of shallow shotgun sequencing with as low as 0.5 million sequences per sample as an alternative to 16S sequencing for large human microbiome studies. We describe a library preparation protocol enabling shallow shotgun sequencing at approximately the same per-sample cost as 16S sequencing. We analyzed multiple real and simulated biological data sets, including two novel human stool samples with ultradeep sequencing of 2.5 billion sequences per sample, and found that shallow shotgun sequencing recovers more-accurate species-level taxonomic and functional profiles of the human microbiome than 16S sequencing. We discuss the inherent limitations of shallow shotgun sequencing and note that 16S sequencing remains a valuable and important method for taxonomic profiling of novel environments. Although deep WMS sequencing remains the gold standard for high-resolution microbiome analysis, we recommend that researchers consider shallow shotgun sequencing as a useful alternative to 16S sequencing for large-scale human microbiome research studies where WMS sequencing may be cost-prohibitive. IMPORTANCE A common refrain in recent microbiome-related academic meetings is that the field needs to move away from broad taxonomic surveys using 16S sequencing and toward more powerful longitudinal studies using shotgun sequencing. However, performing deep shotgun sequencing in large longitudinal studies remains prohibitively expensive for all but the most well-funded research labs and consortia, which leads many researchers to choose 16S sequencing for large studies, followed by deep shotgun sequencing on a subset of targeted samples. Here, we show that shallow- or moderate-depth shotgun sequencing may be used by researchers to obtain species-level taxonomic and functional data at approximately the same cost as amplicon sequencing. While shallow shotgun sequencing is not intended to replace deep shotgun sequencing for strain-level characterization, we recommend that microbiome scientists consider using shallow shotgun sequencing instead of 16S sequencing for large-scale human microbiome studies.}, } @article {pmid30439937, year = {2018}, author = {Jha, AR and Davenport, ER and Gautam, Y and Bhandari, D and Tandukar, S and Ng, KM and Fragiadakis, GK and Holmes, S and Gautam, GP and Leach, J and Sherchand, JB and Bustamante, CD and Sonnenburg, JL}, title = {Gut microbiome transition across a lifestyle gradient in Himalaya.}, journal = {PLoS biology}, volume = {16}, number = {11}, pages = {e2005396}, doi = {10.1371/journal.pbio.2005396}, pmid = {30439937}, issn = {1545-7885}, abstract = {The composition of the gut microbiome in industrialized populations differs from those living traditional lifestyles. However, it has been difficult to separate the contributions of human genetic and geographic factors from lifestyle. Whether shifts away from the foraging lifestyle that characterize much of humanity's past influence the gut microbiome, and to what degree, remains unclear. Here, we characterize the stool bacterial composition of four Himalayan populations to investigate how the gut community changes in response to shifts in traditional human lifestyles. These groups led seminomadic hunting-gathering lifestyles until transitioning to varying levels of agricultural dependence upon farming. The Tharu began farming 250-300 years ago, the Raute and Raji transitioned 30-40 years ago, and the Chepang retain many aspects of a foraging lifestyle. We assess the contributions of dietary and environmental factors on their gut-associated microbes and find that differences in the lifestyles of Himalayan foragers and farmers are strongly correlated with microbial community variation. Furthermore, the gut microbiomes of all four traditional Himalayan populations are distinct from that of the Americans, indicating that industrialization may further exacerbate differences in the gut community. The Chepang foragers harbor an elevated abundance of taxa associated with foragers around the world. Conversely, the gut microbiomes of the populations that have transitioned to farming are more similar to those of Americans, with agricultural dependence and several associated lifestyle and environmental factors correlating with the extent of microbiome divergence from the foraging population. The gut microbiomes of Raute and Raji reveal an intermediate state between the Chepang and Tharu, indicating that divergence from a stereotypical foraging microbiome can occur within a single generation. Our results also show that environmental factors such as drinking water source and solid cooking fuel are significantly associated with the gut microbiome. Despite the pronounced differences in gut bacterial composition across populations, we found little differences in alpha diversity across lifestyles. These findings in genetically similar populations living in the same geographical region establish the key role of lifestyle in determining human gut microbiome composition and point to the next challenging steps of determining how large-scale gut microbiome reconfiguration impacts human biology.}, } @article {pmid30431239, year = {2018}, author = {Berry, D}, title = {Up-close-and-personal with the human microbiome.}, journal = {Environmental microbiology reports}, volume = {}, number = {}, pages = {}, doi = {10.1111/1758-2229.12709}, pmid = {30431239}, issn = {1758-2229}, } @article {pmid30426826, year = {2018}, author = {Daisley, BA and Monachese, M and Trinder, M and Bisanz, JE and Chmiel, JA and Burton, JP and Reid, G}, title = {Immobilization of cadmium and lead by Lactobacillus rhamnosus GR-1 mitigates apical-to-basolateral heavy metal translocation in a Caco-2 model of the intestinal epithelium.}, journal = {Gut microbes}, volume = {}, number = {}, pages = {1-13}, doi = {10.1080/19490976.2018.1526581}, pmid = {30426826}, issn = {1949-0984}, abstract = {Heavy metals are highly toxic elements that contaminate the global food supply and affect human and wildlife health. Purification technologies are often too expensive or not practically applicable for large-scale implementation, especially in impoverished nations where heavy metal contamination is widespread. Lactobacillus rhamnosus GR-1 (LGR-1) was shown in previous work to reduce heavy metal bioaccumulation in a Tanzanian cohort of women and children through indeterminant mechanisms. Here, it was hypothesized that LGR-1 could sequester the heavy metals lead (Pb) and cadmium (Cd), thereby reducing their absorption across intestinal epithelium. LGR-1 and other lactobacilli significantly reduced the amount of Pb and Cd in solution at all concentrations tested (0.5 mg/L - 50 mg/L) and exhibited sustained binding profiles over a 48-hour period. Relative binding efficiency of LGR-1 decreased as Pb concentration increased, with an absolute minimum binding threshold apparent at concentrations of 2 mg/L and above. Electron microscopy revealed that Pb formed irregular cell-surface clusters on LGR-1, while Cd appeared to form intracellular polymeric clusters. Additionally, LGR-1 was able to significantly reduce apical-to-basolateral translocation of Pb and Cd in a Caco-2 model of the intestinal epithelium. These findings demonstrate the absorbent properties of LGR-1 can immobilize Pb and Cd, effectively reducing their translocation across the intestinal epithelium in vitro. Oral administration of heavy metal-binding Lactobacillus spp. (many of which are known human symbionts and strains of established probiotics) may offer a simple and effective means to reduce the amount of heavy metals absorbed from foods in contaminated regions of the world.}, } @article {pmid30423063, year = {2018}, author = {Frioux, C and Fremy, E and Trottier, C and Siegel, A}, title = {Scalable and exhaustive screening of metabolic functions carried out by microbial consortia.}, journal = {Bioinformatics (Oxford, England)}, volume = {34}, number = {17}, pages = {i934-i943}, doi = {10.1093/bioinformatics/bty588}, pmid = {30423063}, issn = {1367-4811}, abstract = {Motivation: The selection of species exhibiting metabolic behaviors of interest is a challenging step when switching from the investigation of a large microbiota to the study of functions effectiveness. Approaches based on a compartmentalized framework are not scalable. The output of scalable approaches based on a non-compartmentalized modeling may be so large that it has neither been explored nor handled so far.

Results: We present the Miscoto tool to facilitate the selection of a community optimizing a desired function in a microbiome by reporting several possibilities which can be then sorted according to biological criteria. Communities are exhaustively identified using logical programming and by combining the non-compartmentalized and the compartmentalized frameworks. The benchmarking of 4.9 million metabolic functions associated with the Human Microbiome Project, shows that Miscoto is suited to screen and classify metabolic producibility in terms of feasibility, functional redundancy and cooperation processes involved. As an illustration of a host-microbial system, screening the Recon 2.2 human metabolism highlights the role of different consortia within a family of 773 intestinal bacteria.

Miscoto source code, instructions for use and examples are available at: https://github.com/cfrioux/miscoto.}, } @article {pmid30420594, year = {2018}, author = {Yost, S and Stashenko, P and Choi, Y and Kukuruzinska, M and Genco, CA and Salama, A and Weinberg, EO and Kramer, CD and Frias-Lopez, J}, title = {Increased virulence of the oral microbiome in oral squamous cell carcinoma revealed by metatranscriptome analyses.}, journal = {International journal of oral science}, volume = {10}, number = {4}, pages = {32}, doi = {10.1038/s41368-018-0037-7}, pmid = {30420594}, issn = {2049-3169}, support = {Evans Center for Interdisciplinary Biomedical Research ARC//Boston University (BU)/ ; Evans Center for Interdisciplinary Biomedical Research ARC//Boston University (BU)/ ; Evans Center for Interdisciplinary Biomedical Research ARC//Boston University (BU)/ ; Evans Center for Interdisciplinary Biomedical Research ARC//Boston University (BU)/ ; Evans Center for Interdisciplinary Biomedical Research ARC//Boston University (BU)/ ; Evans Center for Interdisciplinary Biomedical Research ARC//Boston University (BU)/ ; Evans Center for Interdisciplinary Biomedical Research ARC//Boston University (BU)/ ; Evans Center for Interdisciplinary Biomedical Research ARC//Boston University (BU)/ ; Evans Center for Interdisciplinary Biomedical Research ARC//Boston University (BU)/ ; }, abstract = {Oral squamous cell carcinoma (OSCC) is the most prevalent and most commonly studied oral cancer. However, there is a void regarding the role that the oral microbiome may play in OSCC. Although the relationship between microbial community composition and OSCC has been thoroughly investigated, microbial profiles of the human microbiome in cancer are understudied. Here we performed a small pilot study of community-wide metatranscriptome analysis to profile mRNA expression in the entire oral microbiome in OSCC to reveal molecular functions associated with this disease. Fusobacteria showed a statistically significantly higher number of transcripts at tumour sites and tumour-adjacent sites of cancer patients compared to the healthy controls analysed. Regardless of the community composition, specific metabolic signatures were consistently found in disease. Activities such as iron ion transport, tryptophanase activity, peptidase activities and superoxide dismutase were over-represented in tumour and tumour-adjacent samples when compared to the healthy controls. The expression of putative virulence factors in the oral communities associated with OSCC showed that activities related to capsule biosynthesis, flagellum synthesis and assembly, chemotaxis, iron transport, haemolysins and adhesins were upregulated at tumour sites. Moreover, activities associated with protection against reactive nitrogen intermediates, chemotaxis, flagellar and capsule biosynthesis were also upregulated in non-tumour sites of cancer patients. Although they are preliminary, our results further suggest that Fusobacteria may be the leading phylogenetic group responsible for the increase in expression of virulence factors in the oral microbiome of OSCC patients.}, } @article {pmid30419494, year = {2018}, author = {Ventura Spagnolo, E and Stassi, C and Mondello, C and Zerbo, S and Milone, L and Argo, A}, title = {Forensic microbiology applications: A systematic review.}, journal = {Legal medicine (Tokyo, Japan)}, volume = {36}, number = {}, pages = {73-80}, doi = {10.1016/j.legalmed.2018.11.002}, pmid = {30419494}, issn = {1873-4162}, abstract = {According to the Human Microbiome Project (HMP), a healthy human body contains ten times more microbes than human cells. Microbial communities colonize different organs of the body, playing fundamental roles both in human health and disease. Despite the vast scientific knowledge of the role of microbial communities in a living body, little is known at present about microbial changes occurring after death, thus leading many authors to investigate the composition of the thanatomicrobiome and its potential applications in the forensic field. The aim of the following review is to provide a general overview of the advances of postmortem microbiology research, mainly focusing on the role of microbiological investigations carried out on internal organs and fluids. To this end, a total of 19 studies have been sistematically reviewed, each one chosen according to specific inclusion/exclusion criteria. The selected studies assess the contribution of contamination, postmortem transmigration and agonal spread to microbial isolation from dead body samples, and shed light on the role of postmortem microbiological investigations in several forensic fields, such as cause of death or PMI determination.}, } @article {pmid30417656, year = {2018}, author = {Fonkou, MD and Dufour, JC and Dubourg, G and Raoult, D}, title = {Repertoire of bacterial species cultured from the human oral cavity and respiratory tract.}, journal = {Future microbiology}, volume = {}, number = {}, pages = {}, doi = {10.2217/fmb-2018-0181}, pmid = {30417656}, issn = {1746-0921}, abstract = {While the gut microbiota is currently in the spotlight, the airway microbiome has been recently associated with several pulmonary diseases and carcinogenesis. As there are several biases associated with high-throughput sequencing methods, cultivation techniques are crucial for the investigation of the human microbiome. We thus aimed to build an exhaustive database, including a list of microbes isolated by culture from respiratory specimens, by performing a review of the literature. Herein, we have listed a total of 756 species cultured from the human respiratory tract. This represents 27.23% of the overall bacterial richness captured from human being by culture methods. This repertoire could be valuable for the elucidation of the interactions between the respiratory microbiome and human health.}, } @article {pmid30401779, year = {2018}, author = {Bratburd, JR and Keller, C and Vivas, E and Gemperline, E and Li, L and Rey, FE and Currie, CR}, title = {Gut Microbial and Metabolic Responses to Salmonella enterica Serovar Typhimurium and Candida albicans.}, journal = {mBio}, volume = {9}, number = {6}, pages = {}, doi = {10.1128/mBio.02032-18}, pmid = {30401779}, issn = {2150-7511}, abstract = {The gut microbiota confers resistance to pathogens of the intestinal ecosystem, yet the dynamics of pathogen-microbiome interactions and the metabolites involved in this process remain largely unknown. Here, we use gnotobiotic mice infected with the virulent pathogen Salmonella enterica serovar Typhimurium or the opportunistic pathogen Candida albicans in combination with metagenomics and discovery metabolomics to identify changes in the community and metabolome during infection. To isolate the role of the microbiota in response to pathogens, we compared mice monocolonized with the pathogen, uninfected mice "humanized" with a synthetic human microbiome, or infected humanized mice. In Salmonella-infected mice, by 3 days into infection, microbiome community structure and function changed substantially, with a rise in Enterobacteriaceae strains and a reduction in biosynthetic gene cluster potential. In contrast, Candida-infected mice had few microbiome changes. The LC-MS metabolomic fingerprint of the cecum differed between mice monocolonized with either pathogen and humanized infected mice. Specifically, we identified an increase in glutathione disulfide, glutathione cysteine disulfide, inosine 5'-monophosphate, and hydroxybutyrylcarnitine in mice infected with Salmonella in contrast to uninfected mice and mice monocolonized with Salmonella These metabolites potentially play a role in pathogen-induced oxidative stress. These results provide insight into how the microbiota community members interact with each other and with pathogens on a metabolic level.IMPORTANCE The gut microbiota is increasingly recognized for playing a critical role in human health and disease, especially in conferring resistance to both virulent pathogens such as Salmonella, which infects 1.2 million people in the United States every year (E. Scallan, R. M. Hoekstra, F. J. Angulo, R. V. Tauxe, et al., Emerg Infect Dis 17:7-15, 2011, https://doi.org/10.3201/eid1701.P11101), and opportunistic pathogens like Candida, which causes an estimated 46,000 cases of invasive candidiasis each year in the United States (Centers for Disease Control and Prevention, Antibiotic Resistance Threats in the United States, 2013, 2013). Using a gnotobiotic mouse model, we investigate potential changes in gut microbial community structure and function during infection using metagenomics and metabolomics. We observe that changes in the community and in biosynthetic gene cluster potential occur within 3 days for the virulent Salmonella enterica serovar Typhimurium, but there are minimal changes with a poorly colonizing Candida albicans In addition, the metabolome shifts depending on infection status, including changes in glutathione metabolites in response to Salmonella infection, potentially in response to host oxidative stress.}, } @article {pmid30400268, year = {2018}, author = {Ojo-Okunola, A and Nicol, M and du Toit, E}, title = {Human Breast Milk Bacteriome in Health and Disease.}, journal = {Nutrients}, volume = {10}, number = {11}, pages = {}, doi = {10.3390/nu10111643}, pmid = {30400268}, issn = {2072-6643}, support = {U54HG009824//NIH Office of the Director/ ; 1U01AI110466-01A1//H3Africa U01 AWARD FROM THE NATIONAL INSTITUTES OF HEALTH OF THE USA/ ; OPP1017641; OPP1017579//Bill and Melinda Gates Foundation/ ; }, abstract = {It is well-known that, beyond nutritional components, human breast milk (HBM) contains a wide variety of non-nutritive bio-factors perfectly suited for the growing infant. In the pre-2000 era, HBM was considered sterile and devoid of micro-organisms. Though HBM was not included as part of the human microbiome project launched in 2007, great strides have been made in studying the bacterial diversity of HBM in both a healthy state and diseased state, and in understanding their role in infant health. HBM provides a vast array of beneficial micro-organisms that play a key role in colonizing the infant's mucosal system, including that of the gut. They also have a role in priming the infant's immune system and supporting its maturation. In this review, we provide an in-depth and updated insight into the immunomodulatory, metabolic, and anti-infective role of HBM bacteriome (bacterial community) and its effect on infant health. We also provide key information from the literature by exploring the possible origin of microbial communities in HBM, the bacterial diversity in this niche and the determinants influencing the HBM bacteriome. Lastly, we investigate the role of the HBM bacteriome in maternal infectious disease (human immunodeficiency virus (HIV) and mastitis)), and cancer. Key gaps in HBM bacterial research are also identified.}, } @article {pmid30397357, year = {2018}, author = {Tirosh, O and Conlan, S and Deming, C and Lee-Lin, SQ and Huang, X and , and Su, HC and Freeman, AF and Segre, JA and Kong, HH}, title = {Expanded skin virome in DOCK8-deficient patients.}, journal = {Nature medicine}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41591-018-0211-7}, pmid = {30397357}, issn = {1546-170X}, abstract = {Human microbiome studies have revealed the intricate interplay of host immunity and bacterial communities to achieve homeostatic balance. Healthy skin microbial communities are dominated by bacteria with low viral representation1-3, mainly bacteriophage. Specific eukaryotic viruses have been implicated in both common and rare skin diseases, but cataloging skin viral communities has been limited. Alterations in host immunity provide an opportunity to expand our understanding of microbial-host interactions. Primary immunodeficient patients manifest with various viral, bacterial, fungal, and parasitic infections, including skin infections4. Dedicator of cytokinesis 8 (DOCK8) deficiency is a rare primary human immunodeficiency characterized by recurrent cutaneous and systemic infections, as well as atopy and cancer susceptibility5. DOCK8, encoding a guanine nucleotide exchange factor highly expressed in lymphocytes, regulates actin cytoskeleton, which is critical for migration through collagen-dense tissues such as skin6. Analyzing deep metagenomic sequencing data from DOCK8-deficient skin samples demonstrated a notable increase in eukaryotic viral representation and diversity compared with healthy volunteers. De novo assembly approaches identified hundreds of novel human papillomavirus genomes, illuminating microbial dark matter. Expansion of the skin virome in DOCK8-deficient patients underscores the importance of immune surveillance in controlling eukaryotic viral colonization and infection.}, } @article {pmid30396009, year = {2018}, author = {Woerner, AE and Novroski, NMM and Wendt, FR and Ambers, A and Wiley, R and Schmedes, SE and Budowle, B}, title = {Forensic human identification with targeted microbiome markers using nearest neighbor classification.}, journal = {Forensic science international. Genetics}, volume = {38}, number = {}, pages = {130-139}, doi = {10.1016/j.fsigen.2018.10.003}, pmid = {30396009}, issn = {1878-0326}, abstract = {From the perspective of forensics genetics, the human microbiome is a rich, relatively untapped resource for human identity testing. Since it varies within and among people, and perhaps temporally, the potential forensic applications of the use of the microbiome can exceed that of human identification. However, the same inherent variability in microbial distributions may pose a substantial barrier to forming predictions on an individual as the source of the microbial sample unless stable signatures of the microbiome are identified and targeted. One of the more commonly adopted strategies for microbial human identification relies on quantifying which taxa are present and their respective abundance levels. It remains an open question if such microbial signatures are more individualizing than estimates of the degree of genetic relatedness between microbial samples. This study attempts to address this question by contrasting two prediction strategies. The first approach uses phylogenetic distance to predict the host individual; thus it operates under the premise that microbes within individuals are more closely related than microbes between/among individuals. The second approach uses population genetic measures of diversity at clade-specific markers, serving as a fine-grained assessment of microbial composition and quantification. Both assessments were performed using targeted sequencing of 286 markers from 22 microbial taxa sampled in 51 individuals across three body sites measured in triplicate. Nearest neighbor and reverse nearest neighbor classifiers were constructed based on the pooled data and yielded 71% and 78% accuracy, respectively, when diversity was considered, and performed significantly worse when a phylogenetic distance was used (54% and 63% accuracy, respectively). However, empirical estimates of classification accuracy were 100% when conditioned on a maximum nearest neighbor distance when diversity was used, while identification based on a phylogenetic distance failed to reach saturation. These findings suggest that microbial strain composition is more individualizing than that of a phylogeny, perhaps indicating that microbial composition may be more individualizing than recent common ancestry. One inference that may be drawn from these findings is that host-environment interactions may maintain the targeted microbial profile and that this maintenance may not necessarily be repopulated by intra-individual microbial strains.}, } @article {pmid30392721, year = {2018}, author = {Cogdill, AP and Gaudreau, PO and Arora, R and Gopalakrishnan, V and Wargo, JA}, title = {The Impact of Intratumoral and Gastrointestinal Microbiota on Systemic Cancer Therapy.}, journal = {Trends in immunology}, volume = {39}, number = {11}, pages = {900-920}, doi = {10.1016/j.it.2018.09.007}, pmid = {30392721}, issn = {1471-4981}, abstract = {The human microbiome is a complex aggregate of microorganisms, and their genomes exert a number of influences crucial to the metabolic, immunologic, hormonal, and homeostatic function of the host. Recent work, both in preclinical mouse models and human studies, has shed light on the impact of gut and tumor microbiota on responses to systemic anticancer therapeutics. In light of this, strategies to target the microbiome to improve therapeutic responses are underway, including efforts to target gut and intratumoral microbes. Here, we discuss mechanisms by which microbiota may impact systemic and antitumor immunity, in addition to outstanding questions in the field. A deeper understanding of these is critical as we devise putative strategies to target the microbiome.}, } @article {pmid30390805, year = {2018}, author = {Wang, Q and Yang, F and Jia, H}, title = {Mining the Microbiome for Drug Targets.}, journal = {Methods in enzymology}, volume = {610}, number = {}, pages = {59-72}, doi = {10.1016/bs.mie.2018.09.014}, pmid = {30390805}, issn = {1557-7988}, abstract = {The human microbiome is our "other genome." Implicated in a growing list of complex diseases, for which genomic studies typically explain a portion of the disease susceptibility, the human gut microbiome has been at the spotlight for our understanding of human diseases. As the microbiome is intrinsically more variable than the human genome, it is important to take careful considerations at each step of a study. Here, we put forward our recommendations, which we envision would facilitate identification of true drug targets in the human microbiome in the colon as well as at other body sites.}, } @article {pmid30390741, year = {2018}, author = {Wu, BG and Segal, LN}, title = {The Lung Microbiome and Its Role in Pneumonia.}, journal = {Clinics in chest medicine}, volume = {39}, number = {4}, pages = {677-689}, doi = {10.1016/j.ccm.2018.07.003}, pmid = {30390741}, issn = {1557-8216}, abstract = {The use of next-generation sequencing and multiomic analysis reveals new insights on the identity of microbes in the lower airways blurring the lines between commensals and pathogens. Microbes are not found in isolation; rather they form complex metacommunities where microbe-host and microbe-microbe interactions play important roles on the host susceptibility to pathogens. In addition, the lower airway microbiota exert significant effects on host immune tone. Thus, this review highlights the roles that microbes in the respiratory tract play in the development of pneumonia.}, } @article {pmid30389765, year = {2018}, author = {Junges, R and Sturød, K and Salvadori, G and Åmdal, HA and Chen, T and Petersen, FC}, title = {Characterization of a signaling system in the oral commensal Streptococcus mitis that mediates interspecies communication with the pathogen Streptococcus pneumoniae.}, journal = {Applied and environmental microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1128/AEM.02297-18}, pmid = {30389765}, issn = {1098-5336}, abstract = {Streptococcus mitis is found in the oral cavity and nasopharynx and forms a significant portion of the human microbiome. In this study, in silico analyses indicated the presence of an Rgg/SHP cell-to-cell communication system in S. mitis Although Rgg presented higher similarity to a repressor in Streptococcus pyogenes, auto-inducing assays and an rgg deletion mutant revealed that in S. mitis Rgg acts as an activator. Transcriptome analysis showed that in addition to shp, the system regulates two other downstream genes, comprising a segment of a putative lantibiotic gene cluster that is in a conjugative element locus in different members of the mitis group. Close comparison to a similar lantibiotic gene cluster in Streptococcus pneumoniae indicated that S. mitis lacked the full set of genes. Despite the potential of SHP to trigger a futile cycle of auto-induction, growth was not significantly affected for the rgg mutant under normal or antibiotic stress conditions. The S. mitis SHP was, however, fully functional in promoting cross-species communication and increasing S. pneumoniae surface polysaccharide production, which in this species is regulated by Rgg/SHP. The activity of SHPs produced by both species was detected in co-cultures using a S. mitis reporter strain. In competitive assays, a slight advantage was observed for the rgg mutants. We conclude that the Rgg/SHP system in S. mitis regulates the expression of its own shp, and activates an Rgg/SHP system in S. pneumoniae that regulates surface polysaccharide synthesis. Fundamentally, cross-communication of such systems may have a role during multi-species interactions.IMPORTANCEBacteria secrete signal molecules into the environment which are sensed by other cells when the density reaches a certain threshold. In this study, we describe a communication system in Streptococcus mitis, a commensal species from the oral cavity, which we also found in several species and strains of streptococci from the mitis group. Further, we show that this system can promote cross-communication with S. pneumoniae, a closely-related major human pathogen. Importantly, we show that this cross-communication can take place during co-culture. While the genes regulated in S. mitis are likely part of a futile cycle of activation, the target genes in S. pneumoniae are potentially involved in virulence. The understanding of such complex communication networks can provide important insights into the dynamics of bacterial communities.}, } @article {pmid30384329, year = {2018}, author = {Schooley, RT}, title = {The human microbiome: implications for health and disease, including HIV infection.}, journal = {Topics in antiviral medicine}, volume = {26}, number = {3}, pages = {75-78}, pmid = {30384329}, issn = {2161-5853}, abstract = {Our increased understanding of the human microbiome has brought insight into the role it plays in health and disease, including HIV infection. Studies have shown that the gut microbiome is less diverse in individuals with HIV infection than in noninfected control subjects. Efforts to modify the microbiome to bolster immune reconstitution in people with HIV infection have so far been unsuccessful. The vaginal microbiome affects risk of HIV acquisition, with Lactobacillus dominance being protective compared with vaginosis characterized by larger populations of Gardnerella. The vaginal microbiome might also affect efficacy of topical tenofovir disoproxil fumarate preexposure prophylaxis. This article summarizes a presentation by Robert T. Schooley, MD, at the IAS-USA continuing education program held in San Francisco in May 2018.}, } @article {pmid30377376, year = {2018}, author = {Franzosa, EA and McIver, LJ and Rahnavard, G and Thompson, LR and Schirmer, M and Weingart, G and Lipson, KS and Knight, R and Caporaso, JG and Segata, N and Huttenhower, C}, title = {Species-level functional profiling of metagenomes and metatranscriptomes.}, journal = {Nature methods}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41592-018-0176-y}, pmid = {30377376}, issn = {1548-7105}, abstract = {Functional profiles of microbial communities are typically generated using comprehensive metagenomic or metatranscriptomic sequence read searches, which are time-consuming, prone to spurious mapping, and often limited to community-level quantification. We developed HUMAnN2, a tiered search strategy that enables fast, accurate, and species-resolved functional profiling of host-associated and environmental communities. HUMAnN2 identifies a community's known species, aligns reads to their pangenomes, performs translated search on unclassified reads, and finally quantifies gene families and pathways. Relative to pure translated search, HUMAnN2 is faster and produces more accurate gene family profiles. We applied HUMAnN2 to study clinal variation in marine metabolism, ecological contribution patterns among human microbiome pathways, variation in species' genomic versus transcriptional contributions, and strain profiling. Further, we introduce 'contributional diversity' to explain patterns of ecological assembly across different microbial community types.}, } @article {pmid30374951, year = {2018}, author = {Vinberg, M and Ottesen, NM and Meluken, I and Sørensen, N and Pedersen, O and Kessing, LV and Miskowiak, KW}, title = {Remitted affective disorders and high familial risk of affective disorders associate with aberrant intestinal microbiota.}, journal = {Acta psychiatrica Scandinavica}, volume = {}, number = {}, pages = {}, doi = {10.1111/acps.12976}, pmid = {30374951}, issn = {1600-0447}, support = {//Hørslev Foundation/ ; //The Research fund of the Capital Region of Denmark/ ; //Axel Thomsens Foundation/ ; //Novo Nordisk Foundation/ ; R108-A10015//Lundbeck Foundation/ ; //(Laegevidenskabens fremme) Foundation/ ; //Augustinus Foundation/ ; }, abstract = {OBJECTIVE: Affective disorders seem associated with aberrant intestinal microbiota but whether this pattern also occurs in individuals at increased heritable risk is unknown. We investigated associations between gut microbiota profiles and affective disorders by comparing monozygotic (MZ) twins concordant (affected twins with unipolar or bipolar disorder in remission) and discordant to affective disorders (high-risk) with MZ twins without affective disorders (low-risk).

METHODS: Stool samples were collected from 128 MZ twins and the microbiome was profiled using 16S rDNA sequencing of the V3-V4 region.

RESULTS: Affected twins had a lower diversity and an absence of a specific operational taxonomical unit (OTU) in comparison with low-risk twins. The high-risk twins exhibited the same pattern although the lower diversity was only at a trend level. The OTU belonged to the family Christensenellaceae. The findings were not explained by lifestyle factors (smoking, alcohol consumption, body mass index, or psychotropic medication).

CONCLUSION: Affected twins in remission and high-risk twins presented aberrant gut microbiota with depletion of a specific OTU. If replicated, this reduced relative sequence absence may together with the globally altered microbiota composition act as a vulnerability marker by accentuating the effect of gene-environment interactions in individuals genetically disposed for an affective disorder.}, } @article {pmid30374830, year = {2018}, author = {Pretzl, B and Sälzer, S and Ehmke, B and Schlagenhauf, U and Dannewitz, B and Dommisch, H and Eickholz, P and Jockel-Schneider, Y}, title = {Administration of systemic antibiotics during non-surgical periodontal therapy-a consensus report.}, journal = {Clinical oral investigations}, volume = {}, number = {}, pages = {}, doi = {10.1007/s00784-018-2727-0}, pmid = {30374830}, issn = {1436-3771}, support = {2.2-220.522-97/15_1//Commission for Young Scientists and Gender Equality, University of Wuerzburg/ ; 2.2-220.522-97/2015_1//IZKF/ ; }, abstract = {AIM: The aim of this meta-review was to evaluate whether there is a meaningful clinical benefit regarding the use of systemic adjunctive antibiotics in the treatment of patients with periodontitis. Additionally, a consensus regarding possible recommendations for future administration of antibiotics should be reached.

METHODS: A structured literature search was performed by two independent investigators focusing on systematic reviews (SR) covering adjunctive systemic antibiosis during non-surgical periodontal therapy. Additionally, recent randomized clinical trials (RCT, July 2015 to July 2017) were searched systematically to update the latest SR. Results were summarized and discussed in a plenary to reach a consensus.

RESULTS: Mostly, systematic reviews and RCTs showed a significant positive effect of adjunctive systematic antibiosis compared to controls. These positive effects gain clinical relevance in patients with severe periodontal disease aged 55 years and younger.

CONCLUSION: Systemic antibiotics as an adjunct to non-surgical periodontal therapy should be sensibly administered and restrictively used. Only certain groups of periodontitis patients show a significant and clinically relevant benefit after intake of systemic antibiosis during periodontal therapy.

CLINICAL RELEVANCE: Avoiding antibiotic resistance and possible side effects on the human microbiome should be a focus of dentists and physicians. Thus, a sensible administration of antibiotics is mandatory. This manuscript suggests guidelines for a reasonable use.}, } @article {pmid30367598, year = {2018}, author = {Shi, JY and Huang, H and Zhang, YN and Cao, JB and Yiu, SM}, title = {BMCMDA: a novel model for predicting human microbe-disease associations via binary matrix completion.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 9}, pages = {281}, doi = {10.1186/s12859-018-2274-3}, pmid = {30367598}, issn = {1471-2105}, abstract = {BACKGROUND: Human Microbiome Project reveals the significant mutualistic influence between human body and microbes living in it. Such an influence lead to an interesting phenomenon that many noninfectious diseases are closely associated with diverse microbes. However, the identification of microbe-noninfectious disease associations (MDAs) is still a challenging task, because of both the high cost and the limitation of microbe cultivation. Thus, there is a need to develop fast approaches to screen potential MDAs. The growing number of validated MDAs enables us to meet the demand in a new insight. Computational approaches, especially machine learning, are promising to predict MDA candidates rapidly among a large number of microbe-disease pairs with the advantage of no limitation on microbe cultivation. Nevertheless, a few computational efforts at predicting MDAs are made so far.

RESULTS: In this paper, grouping a set of MDAs into a binary MDA matrix, we propose a novel predictive approach (BMCMDA) based on Binary Matrix Completion to predict potential MDAs. The proposed BMCMDA assumes that the incomplete observed MDA matrix is the summation of a latent parameterizing matrix and a noising matrix. It also assumes that the independently occurring subscripts of observed entries in the MDA matrix follows a binomial model. Adopting a standard mean-zero Gaussian distribution for the nosing matrix, we model the relationship between the parameterizing matrix and the MDA matrix under the observed microbe-disease pairs as a probit regression. With the recovered parameterizing matrix, BMCMDA deduces how likely a microbe would be associated with a particular disease. In the experiment under leave-one-out cross-validation, it exhibits the inspiring performance (AUC = 0.906, AUPR =0.526) and demonstrates its superiority by ~ 7% and ~ 5% improvements in terms of AUC and AUPR respectively in the comparison with the pioneering approach KATZHMDA.

CONCLUSIONS: Our BMCMDA provides an effective approach for predicting MDAs and can be also extended to other similar predicting tasks of binary relationship (e.g. protein-protein interaction, drug-target interaction).}, } @article {pmid30356183, year = {2018}, author = {Vatanen, T and Franzosa, EA and Schwager, R and Tripathi, S and Arthur, TD and Vehik, K and Lernmark, Å and Hagopian, WA and Rewers, MJ and She, JX and Toppari, J and Ziegler, AG and Akolkar, B and Krischer, JP and Stewart, CJ and Ajami, NJ and Petrosino, JF and Gevers, D and Lähdesmäki, H and Vlamakis, H and Huttenhower, C and Xavier, RJ}, title = {The human gut microbiome in early-onset type 1 diabetes from the TEDDY study.}, journal = {Nature}, volume = {562}, number = {7728}, pages = {589-594}, doi = {10.1038/s41586-018-0620-2}, pmid = {30356183}, issn = {1476-4687}, abstract = {Type 1 diabetes (T1D) is an autoimmune disease that targets pancreatic islet beta cells and incorporates genetic and environmental factors1, including complex genetic elements2, patient exposures3 and the gut microbiome4. Viral infections5 and broader gut dysbioses6 have been identified as potential causes or contributing factors; however, human studies have not yet identified microbial compositional or functional triggers that are predictive of islet autoimmunity or T1D. Here we analyse 10,913 metagenomes in stool samples from 783 mostly white, non-Hispanic children. The samples were collected monthly from three months of age until the clinical end point (islet autoimmunity or T1D) in the The Environmental Determinants of Diabetes in the Young (TEDDY) study, to characterize the natural history of the early gut microbiome in connection to islet autoimmunity, T1D diagnosis, and other common early life events such as antibiotic treatments and probiotics. The microbiomes of control children contained more genes that were related to fermentation and the biosynthesis of short-chain fatty acids, but these were not consistently associated with particular taxa across geographically diverse clinical centres, suggesting that microbial factors associated with T1D are taxonomically diffuse but functionally more coherent. When we investigated the broader establishment and development of the infant microbiome, both taxonomic and functional profiles were dynamic and highly individualized, and dominated in the first year of life by one of three largely exclusive Bifidobacterium species (B. bifidum, B. breve or B. longum) or by the phylum Proteobacteria. In particular, the strain-specific carriage of genes for the utilization of human milk oligosaccharide within a subset of B. longum was present specifically in breast-fed infants. These analyses of TEDDY gut metagenomes provide, to our knowledge, the largest and most detailed longitudinal functional profile of the developing gut microbiome in relation to islet autoimmunity, T1D and other early childhood events. Together with existing evidence from human cohorts7,8 and a T1D mouse model9, these data support the protective effects of short-chain fatty acids in early-onset human T1D.}, } @article {pmid30355348, year = {2018}, author = {Tackmann, J and Arora, N and Schmidt, TSB and Rodrigues, JFM and von Mering, C}, title = {Ecologically informed microbial biomarkers and accurate classification of mixed and unmixed samples in an extensive cross-study of human body sites.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {192}, doi = {10.1186/s40168-018-0565-6}, pmid = {30355348}, issn = {2049-2618}, support = {31003A-160095//Swiss National Science Foundation/ ; }, abstract = {BACKGROUND: The identification of body site-specific microbial biomarkers and their use for classification tasks have promising applications in medicine, microbial ecology, and forensics. Previous studies have characterized site-specific microbiota and shown that sample origin can be accurately predicted by microbial content. However, these studies were usually restricted to single datasets with consistent experimental methods and conditions, as well as comparatively small sample numbers. The effects of study-specific biases and statistical power on classification performance and biomarker identification thus remain poorly understood. Furthermore, reliable detection in mixtures of different body sites or with noise from environmental contamination has rarely been investigated thus far. Finally, the impact of ecological associations between microbes on biomarker discovery was usually not considered in previous work.

RESULTS: Here we present the analysis of one of the largest cross-study sequencing datasets of microbial communities from human body sites (15,082 samples from 57 publicly available studies). We show that training a Random Forest Classifier on this aggregated dataset increases prediction performance for body sites by 35% compared to a single-study classifier. Using simulated datasets, we further demonstrate that the source of different microbial contributions in mixtures of different body sites or with soil can be detected starting at 1% of the total microbial community. We apply a biomarker selection method that excludes indirect environmental associations driven by microbe-microbe associations, yielding a parsimonious set of highly predictive taxa including novel biomarkers and excluding many previously reported taxa. We find a considerable fraction of unclassified biomarkers ("microbial dark matter") and observe that negatively associated taxa have a surprisingly high impact on classification performance. We further detect a significant enrichment of rod-shaped, motile, and sporulating taxa for feces biomarkers, consistent with a highly competitive environment.

CONCLUSIONS: Our machine learning model shows strong body site classification performance, both in single-source samples and mixtures, making it promising for tasks requiring high accuracy, such as forensic applications. We report a core set of ecologically informed biomarkers, inferred across a wide range of experimental protocols and conditions, providing the most concise, general, and least biased overview of body site-associated microbes to date.}, } @article {pmid30352623, year = {2018}, author = {Benler, S and Cobián-Güemes, AG and McNair, K and Hung, SH and Levi, K and Edwards, R and Rohwer, F}, title = {A diversity-generating retroelement encoded by a globally ubiquitous Bacteroides phage.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {191}, doi = {10.1186/s40168-018-0573-6}, pmid = {30352623}, issn = {2049-2618}, support = {124351//National Science Foundation/ ; TG-MCB170036//xsede/ ; }, abstract = {BACKGROUND: Diversity-generating retroelements (DGRs) are genetic cassettes that selectively mutate target genes to produce hypervariable proteins. First characterized in Bordetella bacteriophage BPP-1, the DGR creates a hypervariable phage tail fiber that enables host tropism switching. Subsequent surveys for DGRs conclude that the majority identified to date are bacterial or archaeal in origin. This work examines bacteriophage and bacterial genomes for novel phage-encoded DGRs.

RESULTS: This survey discovered 92 DGRs that were only found in phages exhibiting a temperate lifestyle. The majority of phage-encoded DGRs were identified as prophages in bacterial hosts from the phyla Bacteroidetes, Proteobacteria, and Firmicutes. Sequence reads from these previously unidentified prophages were present in viral metagenomes (viromes), indicating these prophages can produce functional viruses. Five phages possessed hypervariable proteins with structural similarity to the tail fiber of BPP-1, whereas the functions of the remaining DGR target proteins were unknown. A novel temperate phage that harbors a DGR cassette targeting a protein of unknown function was induced from Bacteroides dorei. This phage, here named Bacteroides dorei Hankyphage, lysogenizes 13 different Bacteroides species and was present in 34% and 21% of whole-community metagenomes and human-associated viromes, respectively.

CONCLUSIONS: Here, the number of known DGR-containing phages is increased from four to 92. All of these phages exhibit a temperate lifestyle, including a cosmopolitan human-associated phage. Targeted hypervariation by temperate phages may be a ubiquitous mechanism underlying phage-bacteria interaction in the human microbiome.}, } @article {pmid30349509, year = {2018}, author = {Chaudhari, NM and Gautam, A and Gupta, VK and Kaur, G and Dutta, C and Paul, S}, title = {PanGFR-HM: A Dynamic Web Resource for Pan-Genomic and Functional Profiling of Human Microbiome With Comparative Features.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {2322}, doi = {10.3389/fmicb.2018.02322}, pmid = {30349509}, issn = {1664-302X}, abstract = {The conglomerate of microorganisms inhabiting various body-sites of human, known as the human microbiome, is one of the key determinants of human health and disease. Comprehensive pan-genomic and functional analysis approach for human microbiome components can enrich our understanding about impact of microbiome on human health. By utilizing this approach we developed PanGFR-HM (http://www.bioinfo.iicb.res.in/pangfr-hm/) - a novel dynamic web-resource that integrates genomic and functional characteristics of 1293 complete microbial genomes available from Human Microbiome Project. The resource allows users to explore genomic/functional diversity and genome-based phylogenetic relationships between human associated microbial genomes, not provided by any other resource. The key features implemented here include pan-genome and functional analysis of organisms based on taxonomy or body-site, and comparative analysis between groups of organisms. The first feature can also identify probable gene-loss events and significantly over/under represented KEGG/COG categories within pan-genome. The unique second feature can perform comparative genomic, functional and pathways analysis between 4 groups of microbes. The dynamic nature of this resource enables users to define parameters for orthologous clustering and to select any set of organisms for analysis. As an application for comparative feature of PanGFR-HM, we performed a comparative analysis with 67 Lactobacillus genomes isolated from human gut, oral cavity and urogenital tract, and therefore characterized the body-site specific genes, enzymes and pathways. Altogether, PanGFR-HM, being unique in its content and functionality, is expected to provide a platform for microbiome-based comparative functional and evolutionary genomics.}, } @article {pmid30349024, year = {2018}, author = {Chen, Z and Yeoh, YK and Hui, M and Wong, PY and Chan, MCW and Ip, M and Yu, J and Burk, RD and Chan, FKL and Chan, PKS}, title = {Diversity of macaque microbiota compared to the human counterparts.}, journal = {Scientific reports}, volume = {8}, number = {1}, pages = {15573}, doi = {10.1038/s41598-018-33950-6}, pmid = {30349024}, issn = {2045-2322}, abstract = {Studies on the microbial communities in non-human primate hosts provide unique insights in both evolution and function of microbes related to human health and diseases. Using 16S rRNA gene amplicon profiling, we examined the oral, anal and vaginal microbiota in a group of non-captive rhesus macaques (N = 116) and compared the compositions with the healthy communities from Human Microbiome Project. The macaque microbiota was dominated by Bacteroidetes, Firmicutes and Proteobacteria; however, there were marked differences in phylotypes enriched across body sites indicative of strong niche specialization. Compared to human gut microbiota where Bacteroides predominately enriched, the surveyed macaque anal community exhibited increased abundance of Prevotella. In contrast to the conserved human vaginal microbiota extremely dominated by Lactobacillus, the macaque vaginal microbial composition was highly diverse while lactobacilli were rare. A constant decrease of the vaginal microbiota diversity was observed among macaque samples from juvenile, adult without tubectomy, and adult with tubectomy, with the most notable distinction being the enrichment of Halomonas in juvenile and Saccharofermentans in contracepted adults. Both macaque and human oral microbiota were colonized with three most common oral bacterial genera: Streptococcus, Haemophilus and Veillonella, and shared relatively conserved communities to each other. A number of bacteria related to human pathogens were consistently detected in macaques. The findings delineate the range of structure and diversity of microbial communities in a wild macaque population, and enable the application of macaque as an animal model for future characterization of microbes in transmission, genomics and function.}, } @article {pmid30345704, year = {2018}, author = {Ponziani, FR and Putignani, L and Paroni Sterbini, F and Petito, V and Picca, A and Del Chierico, F and Reddel, S and Calvani, R and Marzetti, E and Sanguinetti, M and Gasbarrini, A and Pompili, M}, title = {Influence of hepatitis C virus eradication with direct-acting antivirals on the gut microbiota in patients with cirrhosis.}, journal = {Alimentary pharmacology & therapeutics}, volume = {}, number = {}, pages = {}, doi = {10.1111/apt.15004}, pmid = {30345704}, issn = {1365-2036}, abstract = {BACKGROUND: The cure of hepatitis C virus (HCV) infection may contribute to the reduction of liver fibrosis progression and potentially influence the gut-liver axis.

AIM: To investigate the influence of HCV infection eradication with direct-acting antivirals (DAAs) on the gut microbiota composition as well as on intestinal and systemic inflammatory parameters in patients with cirrhosis.

METHODS: Consecutive patients with HCV-related cirrhosis receiving DAA treatment were included. The gut microbiota composition, intestinal permeability, and inflammation were assessed before treatment and after 1 year. Clinical outcomes such as episodes of decompensation and markers of liver fibrosis were evaluated over a 2-year follow-up period.

RESULTS: The gut microbiota alpha diversity in cirrhotic patients, which was lower than that in healthy subjects, was significantly improved by the cure of HCV infection and a shift in the overall gut microbiota composition was observed compared to baseline. The abundance of potentially pathogenic bacteria (Enterobacteriaceae, Enterococcus, and Staphylococcus) was decreased after treatment. The gut microbiota composition was associated with the inflammatory profile and markers of liver fibrosis. Although a significant reduction in the serum levels of cytokines and chemokines was observed post-DAA treatment, measures of intestinal permeability and inflammation remained unchanged.

CONCLUSIONS: Cure of HCV infection with DAAs in patients with cirrhosis is associated with a modification of the gut microbiota, which correlates with fibrosis and inflammation but does not improve intestinal barrier function.}, } @article {pmid30345066, year = {2018}, author = {Duran-Pinedo, AE and Solbiati, J and Frias-Lopez, J}, title = {The effect of the stress hormone cortisol on the metatranscriptome of the oral microbiome.}, journal = {NPJ biofilms and microbiomes}, volume = {4}, number = {}, pages = {25}, doi = {10.1038/s41522-018-0068-z}, pmid = {30345066}, issn = {2055-5008}, abstract = {Imbalances of the microbiome, also referred to as microbial dysbiosis, could lead to a series of different diseases. One factor that has been shown to lead to dysbiosis of the microbiome is exposure to psychological stressors. Throughout evolution microorganisms of the human microbiome have developed systems for sensing host-associated signals such as hormones associated with those stressors, enabling them to recognize essential changes in their environment, thus changing their expression gene profile to fit the needs of the new environment. The most widely accepted theory explaining the ability of hormones to affect the outcome of an infection involves the suppression of the immune system. Commensal microbiota is involved in stressor-induced immunomodulation, but other biological effects are not yet known. Here we present the impact that cortisol had on the community-wide transcriptome of the oral community. We used a metatranscriptomic approach to obtain first insights into the metabolic changes induced by this stress hormone as well as which members of the oral microbiome respond to the presence of cortisol in the environment. Our findings show that the stress hormone cortisol directly induces shifts in the gene expression profiles of the oral microbiome that reproduce results found in the profiles of expression of periodontal disease and its progression.}, } @article {pmid30342346, year = {2018}, author = {Chen, B and Wang, J and Wang, Y and Zhang, J and Zhao, C and Shen, N and Yang, J and Gai, Z and Zhang, L}, title = {Oral microbiota dysbiosis and its association with Henoch-Schönlein Purpura in children.}, journal = {International immunopharmacology}, volume = {65}, number = {}, pages = {295-302}, doi = {10.1016/j.intimp.2018.10.017}, pmid = {30342346}, issn = {1878-1705}, abstract = {BACKGROUND: The pathogenesis of microbes in allergic diseases has been demonstrated and our previous research indicates that microbiota causing gut disorders in children is associated with Henoch-Schönlein Purpura. However, the role of oral microbiota in Henoch-Schönlein Purpura remains unknown.

METHOD: A total of 164 children were enrolled, of which 98 were patients with HSP and 66 were healthy children. Oral swab samples were collected for DNA extraction and 16S rRNA gene sequencing, then analyzed for oral microbiota composition.

RESULTS: Oral microbiota differed between healthy children and those with HSP. Children with HSP exhibited higher oral microbial diversity and richness than the controls. Firmicutes, Proteobacteria, and Bacteroidetes are the dominant phyla in children with HSP. We used linear discriminant analysis (LDA) effect size (LEfSe) algorithm and detected 21 bacterial taxonomic clades showing statistical differences (12 increased and 9 decreased) in children with HSP. The correlation analyses between clinical data and abundance in microbial community indicated that an abundance of Butyrivibrio sp. negatively correlated with the length of hospital stay (LOS). Haemophilus sp. negatively correlated to IgE and IgM but positively correlated to LOS, with decreasing significantly in patients with HSP. Prevotella positively correlated with IgM. Prevotella nanceiensis positively correlated with IgA, and were abundant in children with HSP.

CONCLUSIONS: These results indicate that children with HSP have significantly different oral microbiota compared to healthy children. Although this study does not imply causality, it is helpful to identify the types and pathways of bacteria that can be used to prevent or treat HSP.}, } @article {pmid30332487, year = {2018}, author = {Wyman, SK and Avila-Herrera, A and Nayfach, S and Pollard, KS}, title = {A most wanted list of conserved microbial protein families with no known domains.}, journal = {PloS one}, volume = {13}, number = {10}, pages = {e0205749}, doi = {10.1371/journal.pone.0205749}, pmid = {30332487}, issn = {1932-6203}, abstract = {The number and proportion of genes with no known function are growing rapidly. To quantify this phenomenon and provide criteria for prioritizing genes for functional characterization, we developed a bioinformatics pipeline that identifies robustly defined protein families with no annotated domains, ranks these with respect to phylogenetic breadth, and identifies them in metagenomics data. We applied this approach to 271 965 protein families from the SFams database and discovered many with no functional annotation, including >118 000 families lacking any known protein domain. From these, we prioritized 6 668 conserved protein families with at least three sequences from organisms in at least two distinct classes. These Function Unknown Families (FUnkFams) are present in Tara Oceans Expedition and Human Microbiome Project metagenomes, with distributions associated with sampling environment. Our findings highlight the extent of functional novelty in sequence databases and establish an approach for creating a "most wanted" list of genes to prioritize for further characterization.}, } @article {pmid30324342, year = {2018}, author = {Waterhouse, M and Hope, B and Krause, L and Morrison, M and Protani, MM and Zakrzewski, M and Neale, RE}, title = {Vitamin D and the gut microbiome: a systematic review of in vivo studies.}, journal = {European journal of nutrition}, volume = {}, number = {}, pages = {}, doi = {10.1007/s00394-018-1842-7}, pmid = {30324342}, issn = {1436-6215}, abstract = {PURPOSE: Variation in the human microbiome has been linked with a variety of physiological functions, including immune regulation and metabolism and biosynthesis of vitamins, hormones, and neurotransmitters. Evidence for extraskeletal effects of vitamin D has been accruing and it has been suggested that the effect of vitamin D on health is partially mediated through the microbiome. We aimed to critically evaluate the evidence linking vitamin D and the gastrointestinal microbiome.

METHODS: We systematically searched the Embase, Web of Science, PubMed and CINAHL databases, including peer-reviewed publications that reported an association between a measure of vitamin D and the gastrointestinal microbiome in humans or experimental animals.

RESULTS: We included 10 mouse and 14 human studies. Mouse studies compared mice fed diets containing different levels of vitamin D (usually high versus low), or vitamin D receptor knockout or Cyp27B1 knockout with wild-type mice. Five mouse studies reported an increase in Bacteroidetes (or taxa within that phylum) in the low vitamin D diet or gene knockout group. Human studies were predominantly observational; all but two of the included studies found some association between vitamin D and the gut microbiome, but the nature of differences observed varied across studies.

CONCLUSIONS: Despite substantial heterogeneity, we found evidence to support the hypothesis that vitamin D influences the composition of the gastrointestinal microbiome. However, the research is limited, having been conducted either in mice or in mostly small, selected human populations. Future research in larger population-based studies is needed to fully understand the extent to which vitamin D modulates the microbiome.}, } @article {pmid30311407, year = {2018}, author = {Bilen, M and Mbogning Fonkou, MD and Khelaifia, S and Tomei, E and Cadoret, F and Daoud, Z and Armstrong, N and Bittar, F and Fournier, PE and Raoult, D and Dubourg, G}, title = {Taxonogenomics description of Parabacteroides timonensis sp. nov. isolated from a human stool sample.}, journal = {MicrobiologyOpen}, volume = {}, number = {}, pages = {e00702}, doi = {10.1002/mbo3.702}, pmid = {30311407}, issn = {2045-8827}, support = {//Région Provence Alpes Côte d'Azur/ ; //European funding FEDER PRIMI/ ; }, abstract = {Intensive efforts have been made to describe the human microbiome and its involvement in health and disease. Culturomics has been recently adapted to target formerly uncultured bacteria and other unclassified bacterial species. This approach enabled us to isolate in the current study a new bacterial species, Parabacteroides timonensis strain Marseille-P3236T , from a stool sample of a healthy 39-year-old pygmy male. This strain, is an anaerobic, gram-negative, nonspore-forming motile rod. Its genome is made up of 6,483,434 bp with 43.41% G+C content, 5046 protein-encoding genes, and 84 RNA genes. We herein provide the full description of Parabacteroides timonensis strain Marseille-P3236T through the taxonogenomic approach.}, } @article {pmid30302512, year = {2018}, author = {Balato, A and Cacciapuoti, S and Di Caprio, R and Marasca, C and Masarà, A and Raimondo, A and Fabbrocini, G}, title = {Human Microbiome: Composition and Role in Inflammatory Skin Diseases.}, journal = {Archivum immunologiae et therapiae experimentalis}, volume = {}, number = {}, pages = {}, doi = {10.1007/s00005-018-0528-4}, pmid = {30302512}, issn = {1661-4917}, abstract = {This review focuses on recent evidences about human microbiome composition and functions, exploring the potential implication of its impairment in some diffuse and invalidating inflammatory skin diseases, such as atopic dermatitis, psoriasis, hidradenitis suppurativa and acne. We analysed current scientific literature, focusing on the current evidences about gut and skin microbiome composition and the complex dialogue between microbes and the host. Finally, we examined the consequences of this dialogue for health and skin diseases. This review highlights how human microbes interact with different anatomic niches modifying the state of immune activation, skin barrier status, microbe-host and microbe-microbe interactions. It also shows as most of the factors affecting gut and skin microorganisms' activity have demonstrated to be effective also in modulating chronic inflammatory skin diseases. More and more evidences demonstrate that human microbiome plays a key role in human health and diseases. It is to be expected that these new insights will translate into diagnostic, therapeutic and preventive measures in the context of personalized/precision medicine.}, } @article {pmid30298527, year = {2018}, author = {Bell, JS and Spencer, JI and Yates, RL and Yee, SA and Jacobs, BM and DeLuca, GC}, title = {From Nose to Gut - The Role of the Microbiome in Neurological Disease.}, journal = {Neuropathology and applied neurobiology}, volume = {}, number = {}, pages = {}, doi = {10.1111/nan.12520}, pmid = {30298527}, issn = {1365-2990}, abstract = {Inflammation and neurodegeneration are key features of many chronic neurological diseases, yet the causative mechanisms underlying these processes are poorly understood. There has been mounting interest in the role of the human microbiome in modulating the inflammatory milieu of the central nervous system in health and disease. To date, most research has focussed on a gut-brain axis, with other mucosal surfaces being relatively neglected. We herein take the novel approach of comprehensively reviewing the roles of the microbiome across several key mucosal interfaces - the nose, mouth, lung, and gut - in health and in Parkinson's disease (PD), Alzheimer's disease (AD) and multiple sclerosis (MS). This review systematically appraises the anatomical and microbiological landscape of each mucosal surface in health and disease before considering relevant mechanisms that may influence the initiation and progression of PD, AD, and MS. The cumulative effects of dysbiosis from the nose to the gut may contribute significantly to neurological disease through a wide variety of mechanisms, including direct translocation of bacteria and their products, and modulation of systemic or central nervous system-specific immunity. This remains an understudied and exciting area for future research and may lead to the development of therapeutic targets for chronic neurological disease. This article is protected by copyright. All rights reserved.}, } @article {pmid30298256, year = {2018}, author = {Macklaim, JM and Gloor, GB}, title = {From RNA-seq to Biological Inference: Using Compositional Data Analysis in Meta-Transcriptomics.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {1849}, number = {}, pages = {193-213}, doi = {10.1007/978-1-4939-8728-3_13}, pmid = {30298256}, issn = {1940-6029}, abstract = {The proper analysis of high-throughput sequencing datasets of mixed microbial communities (meta-transcriptomics) is substantially more complex than for datasets composed of single organisms. Adapting commonly used RNA-seq methods to the analysis of meta-transcriptome datasets can be misleading and not use all the available information in a consistent manner. However, meta-transcriptomic experiments can be investigated in a principled manner using Bayesian probabilistic modeling of the data at a functional level coupled with analysis under a compositional data analysis paradigm. We present a worked example for the differential functional evaluation of mixed-species microbial communities obtained from human clinical samples that were sequenced on an Illumina platform. We demonstrate methods to functionally map reads directly, conduct a compositionally appropriate exploratory data analysis, evaluate differential relative abundance, and finally identify compositionally associated (constant ratio) functions. Using these approaches we have found that meta-transcriptomic functional analyses are highly reproducible and convey significant information regarding the ecosystem.}, } @article {pmid30283425, year = {2018}, author = {Hoggard, M and Vesty, A and Wong, G and Montgomery, JM and Fourie, C and Douglas, RG and Biswas, K and Taylor, MW}, title = {Characterizing the Human Mycobiota: A Comparison of Small Subunit rRNA, ITS1, ITS2, and Large Subunit rRNA Genomic Targets.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {2208}, doi = {10.3389/fmicb.2018.02208}, pmid = {30283425}, issn = {1664-302X}, abstract = {Interest in the human microbiome has increased dramatically in the last decade. However, much of this research has focused on bacteria, while the composition and roles of their fungal counterparts remain less understood. Furthermore, a variety of methodological approaches have been applied, and the comparability between studies is unclear. This study compared four primer pairs targeting the small subunit (SSU) rRNA (18S), ITS1, ITS2, and large subunit (LSU) rRNA (26S) genomic regions for their ability to accurately characterize fungal communities typical of the human mycobiota. All four target regions of 21 individual fungal mock community taxa were capable of being amplified adequately and sequenced. Mixed mock community analyses revealed marked variability in the ability of each primer pair to accurately characterize a complex community. ITS target regions outperformed LSU and SSU. Of the ITS regions, ITS1 failed to generate sequences for Yarrowia lipolytica and all three Malassezia species when in a mixed community. These findings were further supported in studies of human sinonasal and mouse fecal samples. Based on these analyses, previous studies using ITS1, SSU, or LSU markers may omit key taxa that are identified by the ITS2 marker. Of methods commonly used in human mycobiota studies to date, we recommend selection of the ITS2 marker. Further investigation of more recently developed fungal primer options will be essential to ultimately determine the optimal methodological approach by which future human mycobiota studies ought to be standardized.}, } @article {pmid30280754, year = {2018}, author = {Romano, L and Gualtieri, P and Nicoletti, F and Merra, G}, title = {Neurodegenerative disorders, gut human microbiome and diet: future research for prevention and supportive therapies.}, journal = {European review for medical and pharmacological sciences}, volume = {22}, number = {18}, pages = {5771-5772}, pmid = {30280754}, issn = {2284-0729}, } @article {pmid30277147, year = {2018}, author = {Vamanu, E}, title = {Complementary functional strategy for modulation of human gut microbiota.}, journal = {Current pharmaceutical design}, volume = {}, number = {}, pages = {}, doi = {10.2174/1381612824666181001154242}, pmid = {30277147}, issn = {1873-4286}, abstract = {BACKGROUND: Two pathologies commonly associated with gut microbiota dysbiosis are type 2 diabetes and cardiovascular diseases. A disturbance in microbial balance translates into the occurrence of degenerative dysfunctions that are also associated with other pathologies, such as obesity, colon cancer.

METHODS: Thus, the aim of this review was to present the significant findings related to human microbiome modulation via the prebiotic effects of wild edible mushrooms as a complementary strategy to modern treatment.

RESULTS: Since diet and medication are two important causes of microbiome fingerprint modifications, new complementary and alternative methods can include wild edible mushrooms, which serve as functional products, given their properties in modulating the microbial pattern at the colon level. The metagenomic study has enabled the identification of some competitive microbiological and biochemical biomarkers which allow the development of innovative strategies in controlling microbial disbalance from human gut.

CONCLUSION: Certain mushroom species have been approaching and their effects on the microbiota fingerprint of two major target groups are highlighted.}, } @article {pmid30276729, year = {2019}, author = {Perkins, RC}, title = {Making the Case for Functional Proteomics.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {1871}, number = {}, pages = {1-40}, doi = {10.1007/978-1-4939-8814-3_1}, pmid = {30276729}, issn = {1940-6029}, abstract = {"Making the Case for Functional Proteomics" first differentiates the Functional Proteome from the products of genetic protein expression. Qualitatively, the prevalence of posttranslational modifications (PTMs) virtually insures that individual, functional proteins do not equate to their genetic expression counterparts. Quantitatively, considering the frequency of PTMs and a conservative estimate of the number of functional entities arising from protein interactions, the size of the Functional Proteome exceeds that of the human genome by at least two orders of magnitude. The human genome does not, cannot, map the Functional Proteome. Further, the collective genome of the human microbiome dwarfs the human genome. With these facts established, "Making the Case…" proceeds to examine Functional Proteomics (of which both "gene expression" and "epigenetics" are but parts of a larger whole) within the context of Systems Biology, concluding that functionally related networks comprise the dominant motif for biological activity. Creating just such a network focus is essential in not only expanding basic knowledge but also in applying that knowledge in the pragmatic efforts of drug and biomarker development. Outlines for development of drugs and biomarkers, as well as the realization of precision medicine, within a functional proteomics-based, network motif are provided. The chapter proceeds to asses both the knowledge base and the tools to fully embrace Functional Proteomics. Given the decades-long infatuation with the reductionism of genomics, it is not surprising that both the proteomics knowledge base and tools are assessed as poor to fair. However, even a minor shift in research funding and a renewed challenge to methods developers will rapidly improve the current situation. Adoption of the included "Roadmap" will realistically make the twenty-first century the century of a long-awaited revolution in biology.}, } @article {pmid30275573, year = {2018}, author = {Gonzalez, A and Navas-Molina, JA and Kosciolek, T and McDonald, D and Vázquez-Baeza, Y and Ackermann, G and DeReus, J and Janssen, S and Swafford, AD and Orchanian, SB and Sanders, JG and Shorenstein, J and Holste, H and Petrus, S and Robbins-Pianka, A and Brislawn, CJ and Wang, M and Rideout, JR and Bolyen, E and Dillon, M and Caporaso, JG and Dorrestein, PC and Knight, R}, title = {Qiita: rapid, web-enabled microbiome meta-analysis.}, journal = {Nature methods}, volume = {15}, number = {10}, pages = {796-798}, doi = {10.1038/s41592-018-0141-9}, pmid = {30275573}, issn = {1548-7105}, abstract = {Multi-omic insights into microbiome function and composition typically advance one study at a time. However, in order for relationships across studies to be fully understood, data must be aggregated into meta-analyses. This makes it possible to generate new hypotheses by finding features that are reproducible across biospecimens and data layers. Qiita dramatically accelerates such integration tasks in a web-based microbiome-comparison platform, which we demonstrate with Human Microbiome Project and Integrative Human Microbiome Project (iHMP) data.}, } @article {pmid30269615, year = {2018}, author = {Aziz, RK and Hegazy, SM and Yasser, R and Rizkallah, MR and ElRakaiby, MT}, title = {Drug pharmacomicrobiomics and toxicomicrobiomics: from scattered reports to systematic studies of drug-microbiome interactions.}, journal = {Expert opinion on drug metabolism & toxicology}, volume = {14}, number = {10}, pages = {1043-1055}, doi = {10.1080/17425255.2018.1530216}, pmid = {30269615}, issn = {1744-7607}, abstract = {INTRODUCTION: Pharmacomicrobiomics and toxicomicrobiomics study how variations within the human microbiome (the combination of human-associated microbial communities and their genomes) affect drug disposition, action, and toxicity. These emerging fields, interconnecting microbiology, bioinformatics, systems pharmacology, and toxicology, complement pharmacogenomics and toxicogenomics, expanding the scope of precision medicine. Areas covered: This article reviews some of the most recently reported pharmacomicrobiomic and toxicomicrobiomic interactions. Examples include the impact of the human gut microbiota on cardiovascular drugs, natural products, and chemotherapeutic agents, including immune checkpoint inhibitors. Although the gut microbiota has been the most extensively studied, some key drug-microbiome interactions involve vaginal, intratumoral, and environmental bacteria, and are briefly discussed here. Additionally, computational resources, moving the field from cataloging to predicting interactions, are introduced. Expert opinion: The rapid pace of discovery triggered by the Human Microbiome Project is moving pharmacomicrobiomic research from scattered observations to systematic studies focusing on screening microbiome variants against different drug classes. Better representation of all human populations will improve such studies by avoiding sampling bias, and the integration of multiomic studies with designed experiments will allow establishing causation. In the near future, pharmacomicrobiomic testing is expected to be a key step in screening novel drugs and designing precision therapeutics.}, } @article {pmid30269123, year = {2018}, author = {Hattori, M}, title = {[Ecology and function of human microbiomes.].}, journal = {Clinical calcium}, volume = {28}, number = {10}, pages = {1398-1405}, doi = {CliCa181013981405}, pmid = {30269123}, issn = {0917-5857}, abstract = {Hundreds of trillions of bacteria consisting of ~1,000 species reside in various human body sites to form bacterial communities(microbiomes)specific for the sites. In the past decade, the human microbiome research in the world incredibly advanced by development of a culture-independent metagenomic analysis based on next-generation sequencing technologies. Particularly, current studies have revealed that the human gut microbiome is profoundly associated with the host's health and disease.}, } @article {pmid30263058, year = {2018}, author = {Maleki Vareki, S and Chanyi, RM and Abdur-Rashid, K and Brennan, L and Burton, JP}, title = {Moving on from Metchnikoff: thinking about microbiome therapeutics in cancer.}, journal = {Ecancermedicalscience}, volume = {12}, number = {}, pages = {867}, doi = {10.3332/ecancer.2018.867}, pmid = {30263058}, issn = {1754-6605}, abstract = {Precision medicine now needs to also consider the microbiome in oncology treatment. Ingested substances, whether they are a carcinogenic or therapeutic agent, will likely come into contact with the microbiota. Even those delivered extra-intestinally can be influenced beyond xenobiotic metabolism by biochemical factors associated with the microbiota or by an immunological predisposition created by the microbiome. We need to undertake one of the largest paradigm shifts to ever occur in medicine, that is, every drug or ingested substance needs to be re-evaluated for its pharmacological effect post-microbiome interaction. The importance of the microbiome with a focus on the treatment of cancer is discussed. In the near future, it may be possible to specifically manipulate the microbial composition within cancer patients to improve the therapeutic potential of existing oncological agents. However, the current tools to do so are limited. Targeted modulation is likely to be achieved by addition, selective enhancement or depletion of specific microbial types. This may include compounds such as narrow spectrum antimicrobial agents or oligosaccharides that will kill or enhance the bacterial growth of distinct members of the microbiota, respectively. This will stimulate a new era in these fields.}, } @article {pmid30257907, year = {2018}, author = {Munson, E and Carroll, KC}, title = {An Update on the Novel Genera and Species and Revised Taxonomic Status of Bacterial Organisms Described in 2016 and 2017.}, journal = {Journal of clinical microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1128/JCM.01181-18}, pmid = {30257907}, issn = {1098-660X}, abstract = {Recognition and acknowledgment of novel bacterial taxonomy and nomenclature revisions can impact clinical practice, disease epidemiology, and routine clinical microbiology laboratory operations. The Journal of Clinical Microbiology (JCM) herein presents its biannual report summarizing such changes published in the years 2016 and 2017, as published and added by the International Journal of Systematic and Evolutionary Microbiology Noteworthy discussion centers around descriptions of novel Corynebacteriaceae and an anaerobic mycolic-acid-producing bacterium in the suborder Corynebacterineae; revisions within the Propionibacterium, Clostridium, Borrelia, and Enterobacter genera; and, a major reorganization of the family EnterobacteriaceaeJCM intends to sustain this series of reports as advancements in molecular genetics, whole genome sequencing, and studies of the human microbiome will continue to produce novel taxa and clearer understandings of bacterial relatedness.}, } @article {pmid30254254, year = {2018}, author = {Nazaroff, WW}, title = {Embracing microbes in exposure science.}, journal = {Journal of exposure science & environmental epidemiology}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41370-018-0075-4}, pmid = {30254254}, issn = {1559-064X}, abstract = {Although defined more broadly, exposure science has mainly focused on exposures to environmental chemicals and related stressors, such as airborne particulate matter. There is an opportunity for exposure science to contribute more substantially to improving public health by devoting more attention to microorganisms as key stressors and agents in exposure. The discovery that pathogenic microbes cause disease in humans precipitated a revolution in public health science and disease prevention. With a continued global urgency to address spread of pathogenic microbes, contributions of microorganisms to both infectious and noninfectious processes merit more attention from the exposure science community. Today, discoveries of the importance of the human microbiome as a determinant of health and disease are precipitating a second revolution. Emerging knowledge creates a major opportunity to expand the scope of exposure science to incorporate the human microbiome as a target and modulator of exposure. A study committee of the National Academies of Sciences, Engineering, and Medicine has defined a research strategy to address health risks that pertain to the interaction of environmental chemicals with the human microbiome. Some aspects of this strategy pose important challenges and opportunities for the exposure science community.}, } @article {pmid30250232, year = {2018}, author = {Zhao, Y and Chen, B and Li, S and Yang, L and Zhu, D and Wang, Y and Wang, H and Wang, T and Shi, B and Gai, Z and Yang, J and Heng, X and Yang, J and Zhang, L}, title = {Detection and characterization of bacterial nucleic acids in culture-negative synovial tissue and fluid samples from rheumatoid arthritis or osteoarthritis patients.}, journal = {Scientific reports}, volume = {8}, number = {1}, pages = {14305}, doi = {10.1038/s41598-018-32675-w}, pmid = {30250232}, issn = {2045-2322}, support = {31471202//Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.)/ ; ZR2014YL040//Natural Science Foundation of Shandong Province (Shandong Provincial Natural Science Foundation)/ ; }, abstract = {Human intestinal microbes can mediate development of arthritis - Studies indicate that certain bacterial nucleic acids may exist in synovial fluid (SF) and could be involved in arthritis, although the underlying mechanism remains unclear. To characterize potential SF bacterial nucleic acids, we used 16S rRNA gene amplicon sequencing to assess bacterial nucleic acid communities in 15 synovial tissue (ST) and 110 SF samples from 125 patients with rheumatoid arthritis (RA) and 16 ST and 42 SF samples from 58 patients with osteoarthritis (OA). Our results showed an abundant diversity of bacterial nucleic acids in these clinical samples, including presence of Porphyromonas and Bacteroides in all 183 samples. Agrobacterium, Comamonas, Kocuria, Meiothermus, and Rhodoplanes were more abundant in synovial tissues of rheumatoid arthritis (STRA). Atopobium, Phascolarctobacterium, Rhodotorula mucilaginosa, Bacteroides uniformis, Rothia, Megasphaera, Turicibacter, Leptotrichia, Haemophilus parainfluenzae, Bacteroides fragilis, Porphyromonas, and Streptococcus were more abundant in synovial tissues of osteoarthritis (STOA). Veillonella dispar, Haemophilus parainfluenzae, Prevotella copri and Treponema amylovorum were more abundant in synovial fluid of rheumatoid arthritis (SFRA), while Bacteroides caccae was more abundant in the synovial fluid of osteoarthritis (SFOA). Overall, this study confirms existence of bacterial nucleic acids in SF and ST samples of RA and OA lesions and reveals potential correlations with degree of disease.}, } @article {pmid30243649, year = {2018}, author = {Wang, N and Zhu, F and Chen, L and Chen, K}, title = {Proteomics, metabolomics and metagenomics for type 2 diabetes and its complications.}, journal = {Life sciences}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.lfs.2018.09.035}, pmid = {30243649}, issn = {1879-0631}, abstract = {Type 2 diabetes mellitus (T2DM) is one of the most common diseases of endocrine and metabolic disorders, whose mechanism is still largely unknown. Fortunately, various "omics" tools have been employed to better understand the progression pathologies of T2DM and its complications. More specifically, proteomics, metabolomics and metagenomics have played crucial roles in advancing deeper understanding of the physiological processes and regulatory mechanisms of T2DM, such as regulation of signaling pathways perturbed by glucose levels, intestinal microorganism, and inflammation and so on. By analyzing the dynamic change and modification of proteins, proteomics has become an important tool in biology and medicine. Metabolomic analysis can amplify and quantify metabolites in living organisms to reveal the relative relationship between metabolites and physiological and pathological changes. There are also increasing evidences that the human microbiome, specifically the gastrointestinal microbiome have a potential role in the etiology and pathological outcomes of T2DM and its complications. This article summarized and discussed the recent applications of these "omics" tools in finding biomarkers for T2DM and its complications. We also reviewed employing multiple "omics" to further advance our understanding of this pathology. This review will benefit deeper understanding in new therapeutic and/or diagnostic biological target for the discovery of T2DM and its complications.}, } @article {pmid30240894, year = {2018}, author = {Allaband, C and McDonald, D and Vázquez-Baeza, Y and Minich, JJ and Tripathi, A and Brenner, DA and Loomba, R and Smarr, L and Sandborn, WJ and Schnabl, B and Dorrestein, P and Zarrinpar, A and Knight, R}, title = {Microbiome 101: Studying, Analyzing, and Interpreting Gut Microbiome Data for Clinicians.}, journal = {Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.cgh.2018.09.017}, pmid = {30240894}, issn = {1542-7714}, abstract = {Advances in technical capabilities for reading out complex human microbiomes are leading to an explosion of microbiome research, leading in turn to intense interest among clinicians in applying these techniques to their patients. In this review, we discuss the content of the human microbiome, including inter- and intra-subject variability, considerations of study design including important confounding factors, and different methods in the laboratory and on the computer to read out the microbiome and its resulting gene products and metabolites. We highlight several common pitfalls for clinicians, including the expectation that an individual's microbiome will be stable, that diet can induce rapid changes that are large compared to the differences among subjects, that everyone has essentially the same core stool microbiome, and that different laboratory and computational methods will yield essentially the same results. We also highlight the current limitations and future promise of these techniques, with the expectation that an understanding of these considerations will help accelerate the path towards routine clinical application of these techniques developed in research settings.}, } @article {pmid30240703, year = {2018}, author = {Kyburz, A and Fallegger, A and Zhang, X and Altobelli, A and Artola-Boran, M and Borbet, T and Urban, S and Paul, P and Münz, C and Floess, S and Huehn, J and Cover, TL and Blaser, MJ and Taube, C and Müller, A}, title = {Trans-maternal Helicobacter pylori exposure reduces allergic airway inflammation in offspring through regulatory T-cells.}, journal = {The Journal of allergy and clinical immunology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jaci.2018.07.046}, pmid = {30240703}, issn = {1097-6825}, abstract = {BACKGROUND: The trans-maternal exposure to tobacco, microbes, nutrients and other environmental factors shapes the fetal immune system through epigenetic processes. The gastric microbe Helicobacter pylori represents an ancestral constituent of the human microbiota that causes gastric disorders on the one hand, and is inversely associated with allergies and chronic inflammatory conditions on the other.

OBJECTIVE: Here, we investigate the consequences of trans-maternal exposure to H. pylori, in utero and/or during lactation, for susceptibility to viral and bacterial infection, predisposition to allergic airway inflammation, and the development of immune cell populations in the lung and lymphoid organs.

METHODS: We use experimental models of house dust mite- or ovalbumin-induced airway inflammation and influenza A virus or Citrobacter infection along with metagenomics analyses, multi-color flow cytometry and bilsufite pyrosequencing to study the effects of H. pylori on allergy severity and immunological and microbiome correlates thereof.

RESULTS: Perinatal exposure to H. pylori extract, or its immunomodulator VacA, confers robust protective effects against allergic airway inflammation not only in the first, but also the second offspring generation, but does not increase susceptibility to viral or bacterial infection. Immune correlates of allergy protection include skewing of regulatory over effector T-cells, expansion of Treg subsets expressing CXCR3 or RORγt, and demethylation of the FOXP3 locus. The composition and diversity of the gastrointestinal microbiota is measurably affected by perinatal H. pylori exposure.

CONCLUSION: We conclude that exposure to H. pylori has consequences not only for the carrier, but also for subsequent generations that may be exploited for interventional purposes.}, } @article {pmid30230652, year = {2018}, author = {Little, MS and Ervin, SM and Walton, WG and Tripathy, A and Xu, Y and Liu, J and Redinbo, MR}, title = {Active Site Flexibility Revealed in Crystal Structures of Parabacteroides merdae β-Glucuronidase from the Human Gut Microbiome.}, journal = {Protein science : a publication of the Protein Society}, volume = {}, number = {}, pages = {}, doi = {10.1002/pro.3507}, pmid = {30230652}, issn = {1469-896X}, abstract = {β-Glucuronidase (GUS) enzymes in the gastrointestinal tract are involved in maintaining mammalian-microbial symbiosis and can play key roles in drug efficacy and toxicity. Parabacteroides merdae GUS was identified as an abundant mini-Loop 2 (mL2) type GUS enzyme in the Human Microbiome Project gut metagenomic database. Here, we report the crystal structure of P. merdae GUS and highlight the differences between this enzyme and extant structures of gut microbial GUS proteins. We find that P. merdae GUS exhibits a distinct tetrameric quaternary structure and that the mL2 motif traces a unique path within the active site, which also includes two arginines distinctive to this GUS. We observe two states of the P. merdae GUS active site; a loop repositions itself by more than 50 Å to place a functionally-relevant residue into the enzyme's catalytic site. Finally, we find that P. merdae GUS is able to bind to homo- and heteropolymers of the polysaccharide alginic acid. Together, these data broaden our understanding of the structural and functional diversity in the GUS family of enzymes present in the human gut microbiome and point to specialization as an important feature of microbial GUS orthologs. This article is protected by copyright. All rights reserved.}, } @article {pmid30224943, year = {2018}, author = {Randolph, TW and Zhao, S and Copeland, W and Hullar, M and Shojaie, A}, title = {KERNEL-PENALIZED REGRESSION FOR ANALYSIS OF MICROBIOME DATA.}, journal = {The annals of applied statistics}, volume = {12}, number = {1}, pages = {540-566}, doi = {10.1214/17-AOAS1102}, pmid = {30224943}, issn = {1932-6157}, support = {K01 HL124050/HL/NHLBI NIH HHS/United States ; P01 CA168530/CA/NCI NIH HHS/United States ; R01 GM114029/GM/NIGMS NIH HHS/United States ; U01 CA162077/CA/NCI NIH HHS/United States ; }, abstract = {The analysis of human microbiome data is often based on dimension-reduced graphical displays and clusterings derived from vectors of microbial abundances in each sample. Common to these ordination methods is the use of biologically motivated definitions of similarity. Principal coordinate analysis, in particular, is often performed using ecologically defined distances, allowing analyses to incorporate context-dependent, non-Euclidean structure. In this paper, we go beyond dimension-reduced ordination methods and describe a framework of high-dimensional regression models that extends these distance-based methods. In particular, we use kernel-based methods to show how to incorporate a variety of extrinsic information, such as phylogeny, into penalized regression models that estimate taxonspecific associations with a phenotype or clinical outcome. Further, we show how this regression framework can be used to address the compositional nature of multivariate predictors comprised of relative abundances; that is, vectors whose entries sum to a constant. We illustrate this approach with several simulations using data from two recent studies on gut and vaginal microbiomes. We conclude with an application to our own data, where we also incorporate a significance test for the estimated coefficients that represent associations between microbial abundance and a percent fat.}, } @article {pmid30223687, year = {2018}, author = {Lin, H and He, QY and Shi, L and Sleeman, M and Baker, MS and Nice, EC}, title = {Proteomics and the microbiome: pitfalls and potential.}, journal = {Expert review of proteomics}, volume = {}, number = {}, pages = {1-11}, doi = {10.1080/14789450.2018.1523724}, pmid = {30223687}, issn = {1744-8387}, abstract = {INTRODUCTION: Human symbiotic microbiota are now known to play important roles in human health and disease. Significant progress in our understanding of the human microbiome has been driven by recent technological advances in the fields of genomics, transcriptomics, and proteomics. As a complementary method to metagenomics, proteomics is enabling detailed protein profiling of the microbiome to decipher its structure and function and to analyze its relationship with the human body. Fecal proteomics is being increasingly applied to discover and validate potential health and disease biomarkers, and Therapeutic Goods Administration (TGA)-approved instrumentation and a range of clinical assays are being developed that will collectively play key roles in advancing personalized medicine. Areas covered: This review will introduce the complexity of the microbiome and its role in health and disease (in particular the gastrointestinal tract or gut microbiome), discuss current genomic and proteomic methods for studying this system, including the discovery of potential biomarkers, and outline the development of clinically accepted protocols leading to personalized medicine. Expert commentary: Recognition of the important role the microbiome plays in both health and disease is driving current research in this key area. A proteogenomics approach will be essential to unravel the biologies underlying this complex network.}, } @article {pmid30218543, year = {2018}, author = {Zhan, X and Xue, L and Zheng, H and Plantinga, A and Wu, MC and Schaid, DJ and Zhao, N and Chen, J}, title = {A small-sample kernel association test for correlated data with application to microbiome association studies.}, journal = {Genetic epidemiology}, volume = {}, number = {}, pages = {}, doi = {10.1002/gepi.22160}, pmid = {30218543}, issn = {1098-2272}, support = {//US Public Health Service/ ; GM065450//National Institutes of Health/ ; //Mayo Clinic Center for Individualized Medicine/ ; }, abstract = {Recent research has highlighted the importance of the human microbiome in many human disease and health conditions. Most current microbiome association analyses focus on unrelated samples; such methods are not appropriate for analysis of data collected from more advanced study designs such as longitudinal and pedigree studies, where outcomes can be correlated. Ignoring such correlations can sometimes lead to suboptimal results or even possibly biased conclusions. Thus, new methods to handle correlated outcome data in microbiome association studies are needed. In this paper, we propose the correlated sequence kernel association test (CSKAT) to address such correlations using the linear mixed model. Specifically, random effects are used to account for the outcome correlations and a variance component test is used to examine the microbiome effect. Compared to existing genetic association tests for longitudinal and family samples, we implement a correction procedure to better calibrate the null distribution of the score test statistic to accommodate the small sample size nature of data collected from a typical microbiome study. Comprehensive simulation studies are conducted to demonstrate the validity and efficiency of our method, and we show that CSKAT achieves a higher power than existing methods while correctly controlling the Type I error rate. We also apply our method to a microbiome data set collected from a UK twin study to illustrate its potential usefulness. A free implementation of our method in R software is available at https://github.com/jchen1981/SSKAT.}, } @article {pmid30214898, year = {2018}, author = {Trinh, P and Zaneveld, JR and Safranek, S and Rabinowitz, PM}, title = {One Health Relationships Between Human, Animal, and Environmental Microbiomes: A Mini-Review.}, journal = {Frontiers in public health}, volume = {6}, number = {}, pages = {235}, doi = {10.3389/fpubh.2018.00235}, pmid = {30214898}, issn = {2296-2565}, support = {T32 ES015459/ES/NIEHS NIH HHS/United States ; }, abstract = {The One Health concept stresses the ecological relationships between human, animal, and environmental health. Much of the One Health literature to date has examined the transfer of pathogens from animals (e.g., emerging zoonoses) and the environment to humans. The recent rapid development of technology to perform high throughput DNA sequencing has expanded this view to include the study of entire microbial communities. Applying the One Health approach to the microbiome allows for consideration of both pathogenic and non-pathogenic microbial transfer between humans, animals, and the environment. We review recent research studies of such transmission, the molecular and statistical methods being used, and the implications of such microbiome relationships for human health. Our review identified evidence that the environmental microbiome as well as the microbiome of animals in close contact can affect both the human microbiome and human health outcomes. Such microbiome transfer can take place in the household as well as the workplace setting. Urbanization of built environments leads to changes in the environmental microbiome which could be a factor in human health. While affected by environmental exposures, the human microbiome also can modulate the response to environmental factors through effects on metabolic and immune function. Better understanding of these microbiome interactions between humans, animals, and the shared environment will require continued development of improved statistical and ecological modeling approaches. Such enhanced understanding could lead to innovative interventions to prevent and manage a variety of human health and disease states.}, } @article {pmid30212271, year = {2018}, author = {Ossorio, PN and Zhou, Y}, title = {Regulating stool for microbiota transplantation.}, journal = {Gut microbes}, volume = {}, number = {}, pages = {1-4}, doi = {10.1080/19490976.2018.1502537}, pmid = {30212271}, issn = {1949-0984}, abstract = {In 2017 Gut Microbes published "A proposed definition of microbiota transplantation for regulatory purposes," in which the authors suggest that regulators should draw a line between microbiota transplants and biologic drugs composed of microbial communities (or other products derived from the human microbiome). They develop a definition of microbiota transplantation (MT) to help regulators draw such a line, and suggest that MT need not be, and cannot be, regulated as a biologic drug (a live biotherapeutic product). However, an agency's regulatory scrutiny of a medical product should be commensurate with that product's degree of risk to patients. Products for MT, such as stool, are likely to be as or more dangerous than more highly manipulated microbial products that scientists and regulators agree should be regulated as biologic drugs. Therefore, we argue that MT, as defined by the authors, should receive the same regulatory oversight as any other biologic product intended to cure, mitigate, treat, or prevent disease. We also suggest that regulators might not be able to operationalize the proposed definition of MT.}, } @article {pmid30211213, year = {2018}, author = {Alves, LF and Westmann, CA and Lovate, GL and de Siqueira, GMV and Borelli, TC and Guazzaroni, ME}, title = {Metagenomic Approaches for Understanding New Concepts in Microbial Science.}, journal = {International journal of genomics}, volume = {2018}, number = {}, pages = {2312987}, doi = {10.1155/2018/2312987}, pmid = {30211213}, issn = {2314-436X}, abstract = {Over the past thirty years, since the dawn of metagenomic studies, a completely new (micro) universe was revealed, with the potential to have profound impacts on many aspects of the society. Remarkably, the study of human microbiome provided a new perspective on a myriad of human traits previously regarded as solely (epi-) genetically encoded, such as disease susceptibility, immunological response, and social and nutritional behaviors. In this context, metagenomics has established a powerful framework for understanding the intricate connections between human societies and microbial communities, ultimately allowing for the optimization of both human health and productivity. Thus, we have shifted from the old concept of microbes as harmful organisms to a broader panorama, in which the signal of the relationship between humans and microbes is flexible and directly dependent on our own decisions and practices. In parallel, metagenomics has also been playing a major role in the prospection of "hidden" genetic features and the development of biotechnological applications, through the discovery of novel genes, enzymes, pathways, and bioactive molecules with completely new or improved biochemical functions. Therefore, this review highlights the major milestones over the last three decades of metagenomics, providing insights into both its potentialities and current challenges.}, } @article {pmid30205462, year = {2018}, author = {Hidalgo-Cantabrana, C and Sanozky-Dawes, R and Barrangou, R}, title = {Insights into the Human Virome Using CRISPR Spacers from Microbiomes.}, journal = {Viruses}, volume = {10}, number = {9}, pages = {}, doi = {10.3390/v10090479}, pmid = {30205462}, issn = {1999-4915}, support = {support//North Carolina Agricultural Foundation/International ; internal support//North Carolina State University/International ; }, abstract = {Due to recent advances in next-generation sequencing over the past decade, our understanding of the human microbiome and its relationship to health and disease has increased dramatically. Yet, our insights into the human virome, and its interplay with important microbes that impact human health, is relatively limited. Prokaryotic and eukaryotic viruses are present throughout the human body, comprising a large and diverse population which influences several niches and impacts our health at various body sites. The presence of prokaryotic viruses like phages, has been documented at many different body sites, with the human gut being the richest ecological niche. Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and associated proteins constitute the adaptive immune system of bacteria, which prevents attack by invasive nucleic acid. CRISPR-Cas systems function by uptake and integration of foreign genetic element sequences into the CRISPR array, which constitutes a genomic archive of iterative vaccination events. Consequently, CRISPR spacers can be investigated to reconstruct interplay between viruses and bacteria, and metagenomic sequencing data can be exploited to provide insights into host-phage interactions within a niche. Here, we show how the CRISPR spacer content of commensal and pathogenic bacteria can be used to determine the evidence of their phage exposure. This framework opens new opportunities for investigating host-virus dynamics in metagenomic data, and highlights the need to dedicate more efforts for virome sampling and sequencing.}, } @article {pmid30205429, year = {2018}, author = {Hendler, R and Zhang, Y}, title = {Probiotics in the Treatment of Colorectal Cancer.}, journal = {Medicines (Basel, Switzerland)}, volume = {5}, number = {3}, pages = {}, doi = {10.3390/medicines5030101}, pmid = {30205429}, issn = {2305-6320}, abstract = {The human microbiome plays many roles in inflammation, drug metabolism, and even the development of cancer that we are only beginning to understand. Colorectal cancer has been a focus for study in this field as its pathogenesis and its response to treatment have both been linked to the functioning of microbiota. This literature review evaluates the animal and human studies that have explored this relationship. By manipulating the microbiome with interventions such as probiotic administration, we may be able to reduce colorectal cancer risk and improve the safety and effectiveness of cancer therapy even though additional clinical research is still necessary.}, } @article {pmid30197908, year = {2017}, author = {Xia, Y and Sun, J}, title = {Hypothesis Testing and Statistical Analysis of Microbiome.}, journal = {Genes & diseases}, volume = {4}, number = {3}, pages = {138-148}, doi = {10.1016/j.gendis.2017.06.001}, pmid = {30197908}, issn = {2352-4820}, support = {R01 DK105118/DK/NIDDK NIH HHS/United States ; R01 DK114126/DK/NIDDK NIH HHS/United States ; }, abstract = {After the initiation of Human Microbiome Project in 2008, various biostatistic and bioinformatic tools for data analysis and computational methods have been developed and applied to microbiome studies. In this review and perspective, we discuss the research and statistical hypotheses in gut microbiome studies, focusing on mechanistic concepts that underlie the complex relationships among host, microbiome, and environment. We review the current available statistic tools and highlight recent progress of newly developed statistical methods and models. Given the current challenges and limitations in biostatistic approaches and tools, we discuss the future direction in developing statistical methods and models for the microbiome studies.}, } @article {pmid30196160, year = {2018}, author = {Dong, TS and Gupta, A}, title = {Influence of Early Life, Diet, and the Environment on the Microbiome.}, journal = {Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.cgh.2018.08.067}, pmid = {30196160}, issn = {1542-7714}, abstract = {Advances in sequencing technology and bioinformatics have greatly enhanced our ability to understand the human microbiome. Over the last decade, a growing body of literature has linked nutrition and the environment to the microbiome and is now thought to be an important contributor to overall health. This paper reviews the literature from the past 10 years to highlight the influence of environmental factors such as diet, early life adversity and stress in shaping and modifying our microbiome towards health and disease. The review shows that many factors such as the mode of delivery, breast milk, stress, diet and medications can greatly influence the development of our gut microbiome and potentially make us more prone to certain diseases. By incorporating environmental factors into models that study the microbiome in the setting of health and disease, may provide a better understanding of disease and potentially new areas of treatment. To highlight this, we will additionally explore the role of the environment and the microbiome in the development of obesity and functional bowel disorders.}, } @article {pmid30195150, year = {2018}, author = {Sharma, A and Gilbert, JA}, title = {Microbial exposure and human health.}, journal = {Current opinion in microbiology}, volume = {44}, number = {}, pages = {79-87}, doi = {10.1016/j.mib.2018.08.003}, pmid = {30195150}, issn = {1879-0364}, abstract = {The human body comprises of micro-ecosystem made up of trillions of microbes (i.e. bacteria, archaea, fungi, protists and viruses). The total microbial gene content, which is referred to as the human microbiome, is fundamental to human physiology and immunity. There exists an intricate relationship between the surrounding microbial world (i.e. the environment) and the endogenous human microbiome, mediated by the immune system. Disrupting this relationship can a profound effect on human health and disease. Understanding how microbial exposure influences immune response and the feedback on endogenous microbial metabolic activity could have profound implications for the development of novel microbial therapeutics. The term 'microbial exposure' is used generally to refer to exogenous environmental microbial interaction, while 'exposome' accounts for both the environmental exposures and the impact of lifestyle-associated microbial impacts, such as diet influences on endogenous microbial metabolism. In this review, we focus on how environment and lifestyle-associated microbial exposures shape the human immune system and microbiome, and how the resulting changes can shape human health, especially during critical developmental windows, that is prenatal, postnatal and adult. We conclude this review by proposing approaches to characterize the microbial exposome so as to accelerate the development of a precision microbial therapeutics for both practical and clinical intervention.}, } @article {pmid30189627, year = {2018}, author = {Di Francesco, L and Di Girolamo, F and Mennini, M and Masotti, A and Salvatori, G and Rigon, G and Signore, F and Pietrantoni, E and Scapaticci, M and Lante, I and Goffredo, BM and Mazzina, O and Elbousify, AI and Roncada, P and Dotta, A and Fiocchi, A and Putignani, L}, title = {A MALDI-TOF MS Approach for Mammalian, Human, and Formula Milks' Profiling.}, journal = {Nutrients}, volume = {10}, number = {9}, pages = {}, doi = {10.3390/nu10091238}, pmid = {30189627}, issn = {2072-6643}, support = {I Fellowship Program//San Camillo Hospital, Treviso, Italy/ ; }, abstract = {Human milk composition is dynamic, and substitute formulae are intended to mimic its protein content. The purpose of this study was to investigate the potentiality of matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF MS), followed by multivariate data analyses as a tool to analyze the peptide profiles of mammalian, human, and formula milks. Breast milk samples from women at different lactation stages (2 (n = 5), 30 (n = 6), 60 (n = 5), and 90 (n = 4) days postpartum), and milk from donkeys (n = 4), cows (n = 4), buffaloes (n = 7), goats (n = 4), ewes (n = 5), and camels (n = 2) were collected. Different brands (n = 4) of infant formulae were also analyzed. Protein content (<30 kDa) was analyzed by MS, and data were exported for statistical elaborations. The mass spectra for each milk closely clustered together, whereas different milk samples resulted in well-separated mass spectra. Human samples formed a cluster in which colostrum constituted a well-defined subcluster. None of the milk formulae correlated with animal or human milk, although they were specifically characterized and correlated well with each other. These findings propose MALDI-TOF MS milk profiling as an analytical tool to discriminate, in a blinded way, different milk types. As each formula has a distinct specificity, shifting a baby from one to another formula implies a specific proteomic exposure. These profiles may assist in milk proteomics for easiness of use and minimization of costs, suggesting that the MALDI-TOF MS pipelines may be useful for not only milk adulteration assessments but also for the characterization of banked milk specimens in pediatric clinical settings.}, } @article {pmid30183502, year = {2018}, author = {Strouse, C and Mangalam, A and Zhang, J}, title = {Bugs in the system: bringing the human microbiome to bear in cancer immunotherapy.}, journal = {Gut microbes}, volume = {}, number = {}, pages = {1-4}, doi = {10.1080/19490976.2018.1511665}, pmid = {30183502}, issn = {1949-0984}, support = {P30 CA086862/CA/NCI NIH HHS/United States ; }, abstract = {The influence of the composition of the human microbiome on the efficacy of cancer directed immunotherapies, such as antibodies directed against the programmed cell death 1 protein (PD-1) or its ligand (PD-L1), has garnered increasing attention as the role of immunotherapies in the care of cancer has grown. Dysbiosis (altered microbiota) has recently been reported to adversely affect the efficacy of cancer directed immunotherapies, and correction of this dysbiosis has the potential to improve the efficacy of these treatments. However, the exact mechanisms underlying this relationship remains unknown. Current methods for characterizing the microbiome likely capture only a small portion of the highly complex interaction between the microbiome and the immune system. Here we discuss the recent reports of the influence of dysbiosis on cancer immunotherapy, methods to more fully characterize the interaction between the microbiome and the immune system, and methods of modulating the immune system to improve the efficacy of cancer immunotherapy.}, } @article {pmid30181300, year = {2018}, author = {Neil, JA and Cadwell, K}, title = {The Intestinal Virome and Immunity.}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, volume = {201}, number = {6}, pages = {1615-1624}, doi = {10.4049/jimmunol.1800631}, pmid = {30181300}, issn = {1550-6606}, support = {R01 AI121244/AI/NIAID NIH HHS/United States ; R01 DK093668/DK/NIDDK NIH HHS/United States ; R01 DK103788/DK/NIDDK NIH HHS/United States ; R01 HL123340/HL/NHLBI NIH HHS/United States ; }, abstract = {The composition of the human microbiome is considered a major source of interindividual variation in immunity and, by extension, susceptibility to diseases. Intestinal bacteria have been the major focus of research. However, diverse communities of viruses that infect microbes and the animal host cohabitate the gastrointestinal tract and collectively constitute the gut virome. Although viruses are typically investigated as pathogens, recent studies highlight a relationship between the host and animal viruses in the gut that is more akin to host-microbiome interactions and includes both beneficial and detrimental outcomes for the host. These viruses are likely sources of immune variation, both locally and extraintestinally. In this review, we describe the components of the gut virome, in particular mammalian viruses, and their ability to modulate host responses during homeostasis and disease.}, } @article {pmid30180541, year = {2018}, author = {Hill, AB and Beitelshees, M and Nayerhoda, R and Pfeifer, BA and Jones, CH}, title = {Engineering a Next-Generation Glycoconjugate-Like Streptococcus pneumoniae Vaccine.}, journal = {ACS infectious diseases}, volume = {}, number = {}, pages = {}, doi = {10.1021/acsinfecdis.8b00100}, pmid = {30180541}, issn = {2373-8227}, abstract = {We detail the development of a next-generation Streptococcus pneumoniae liposomal encapsulation of polysaccharides (LEPS) vaccine, with design characteristics geared toward best-in-class efficacy. The first generation LEPS vaccine, which contained 20 encapsulated pneumococcal capsular polysaccharides (CPSs) and two surface-displayed virulence-associated proteins (GlpO and PncO), enabling prophylactic potency against 70+ serotypes of Streptococcus pneumoniae (the causative agent of pneumococcal disease), was rationally redesigned for advanced clinical readiness and best-in-class coverage. In doing so, the virulent-specific GlpO protein antigen was removed from the final formulation due to off-target immunogenicity toward bacterial species within the human microbiome, while directed protection was maintained by increasing the dose of PncO from 17 to 68 μg. LEPS formulation parameters also readily facilitated an increase in CPS valency (to a total of 24) and systematic variation in protein-liposome attachment mechanisms in anticipation of clinical translation. An additional safety assessment study demonstrated that LEPS does not exhibit appreciable toxicological effects even when administered at ten times the effective dose. In summary, this new design offers the broadest, safest, and most-complete protection while maintaining desirable glycoconjugate-like features, positioning the LEPS vaccine platform for clinical success and a global health impact.}, } @article {pmid30178250, year = {2018}, author = {Riscuta, G and Xi, D and Pierre-Victor, D and Starke-Reed, P and Khalsa, J and Duffy, L}, title = {Diet, Microbiome, and Epigenetics in the Era of Precision Medicine.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {1856}, number = {}, pages = {141-156}, doi = {10.1007/978-1-4939-8751-1_8}, pmid = {30178250}, issn = {1940-6029}, abstract = {Precision medicine is a revolutionary approach to disease prevention and treatment that takes into account individual differences in lifestyle, environment, and biology. The US National Institutes of Health has recently launched The All of Us Research Program (2016) to extend precision medicine to all diseases by building a national research cohort of one million or more US participants. This review is limited to how the human microbiome factors into precision medicine from the applied aspect of preventing and managing cancer. The Precision Medicine Initiative was established in an effort to address particular characteristics of each person with the aim to increase the effectiveness of medical interventions in terms of prevention and treatment of multiple diseases including cancer. Many factors contribute to the response to an intervention. The microbiome and microbially produced metabolites are capable of epigenetic modulation of gene activity, and can influence the response through these mechanisms. The fact that diet has an impact on microbiome implies that it will also affect the epigenetic mechanisms involving microbiota. In this chapter, we review some major epigenetic mechanisms, notably DNA methylation, chromatin remodeling and histone modification, and noncoding RNA, implicated in cancer prevention and treatment. Several examples of how microbially produced metabolites from food influence cancer risk and treatment response through epigenetic mechanisms will be discussed. Some challenges include the limited understanding of how diet shapes the microbiome and how to best evaluate those changes since both, diet and the microbiota, exhibit daily and seasonal variations. Ongoing research seeks to understand the relationship between the human microbiome and multiple diseases including cancer.}, } @article {pmid30177740, year = {2018}, author = {Lee, JYH and Monk, IR and Gonçalves da Silva, A and Seemann, T and Chua, KYL and Kearns, A and Hill, R and Woodford, N and Bartels, MD and Strommenger, B and Laurent, F and Dodémont, M and Deplano, A and Patel, R and Larsen, AR and Korman, TM and Stinear, TP and Howden, BP}, title = {Global spread of three multidrug-resistant lineages of Staphylococcus epidermidis.}, journal = {Nature microbiology}, volume = {3}, number = {10}, pages = {1175-1185}, doi = {10.1038/s41564-018-0230-7}, pmid = {30177740}, issn = {2058-5276}, abstract = {Staphylococcus epidermidis is a conspicuous member of the human microbiome, widely present on healthy skin. Here we show that S. epidermidis has also evolved to become a formidable nosocomial pathogen. Using genomics, we reveal that three multidrug-resistant, hospital-adapted lineages of S. epidermidis (two ST2 and one ST23) have emerged in recent decades and spread globally. These lineages are resistant to rifampicin through acquisition of specific rpoB mutations that have become fixed in the populations. Analysis of isolates from 96 institutions in 24 countries identified dual D471E and I527M RpoB substitutions to be the most common cause of rifampicin resistance in S. epidermidis, accounting for 86.6% of mutations. Furthermore, we reveal that the D471E and I527M combination occurs almost exclusively in isolates from the ST2 and ST23 lineages. By breaching lineage-specific DNA methylation restriction modification barriers and then performing site-specific mutagenesis, we show that these rpoB mutations not only confer rifampicin resistance, but also reduce susceptibility to the last-line glycopeptide antibiotics, vancomycin and teicoplanin. Our study has uncovered the previously unrecognized international spread of a near pan-drug-resistant opportunistic pathogen, identifiable by a rifampicin-resistant phenotype. It is possible that hospital practices, such as antibiotic monotherapy utilizing rifampicin-impregnated medical devices, have driven the evolution of this organism, once trivialized as a contaminant, towards potentially incurable infections.}, } @article {pmid30175072, year = {2018}, author = {Meng, S and Chen, B and Yang, J and Wang, J and Zhu, D and Meng, Q and Zhang, L}, title = {Study of Microbiomes in Aseptically Collected Samples of Human Breast Tissue Using Needle Biopsy and the Potential Role of in situ Tissue Microbiomes for Promoting Malignancy.}, journal = {Frontiers in oncology}, volume = {8}, number = {}, pages = {318}, doi = {10.3389/fonc.2018.00318}, pmid = {30175072}, issn = {2234-943X}, abstract = {Mounting evidence suggests that changes in microbiome are linked to development of cancer and its aggressiveness. Microbiome profiles in human breast tissue previously presumed to be sterile, have recently been characterized using high-throughput technologies. Recent findings of microbiome variation between benign and malignant disease provides a rationale for exploring microbiomes associated with cancer during tumor progression. We assessed microbiomes of aseptically collected human breast tissue samples in this study, using needle biopsy from patients with benign and malignant tumors of different histological grading, using 16S rRNA gene amplicon sequencing. This is consistent with previous studies, and our results identified distinct microbiome profiles in breast tissues from women with cancer as compared to women with benign breast disease in Chinese cohorts. The enriched microbial biomarkers in malignant tissue included genus Propionicimonas and families Micrococcaceae, Caulobacteraceae, Rhodobacteraceae, Nocardioidaceae, Methylobacteriaceae, which appeared to be ethno-specific. Further, we compared microbiome profiles in malignant tissues of three different histological grades. The relative abundance of family Bacteroidaceae decreased and that of genus Agrococcus increased with the development of malignancy. KEGG pathways inferred by PICRUSt showed that biotin and glycerophospholipid metabolism had significant differences in all three grades. Glycerophospholipid and ribosome biogenesis increased in grade III tissue as compared to grades I and II. Flavonoid biosynthesis significantly decreased in grade III tissue. The specific correlation of these potential microbial biomarkers and indicated pathways with advanced disease could have broad implications in the diagnosis and staging of breast cancer. Further large-cohort investigation of the breast cancer microbiome and its potential mechanism in breast cancer development are essential.}, } @article {pmid30169121, year = {2018}, author = {Willis-Owen, SAG and Cookson, WOC and Moffatt, MF}, title = {The Genetics and Genomics of Asthma.}, journal = {Annual review of genomics and human genetics}, volume = {19}, number = {}, pages = {223-246}, doi = {10.1146/annurev-genom-083117-021651}, pmid = {30169121}, issn = {1545-293X}, abstract = {Asthma is a common, clinically heterogeneous disease with strong evidence of heritability. Progress in defining the genetic underpinnings of asthma, however, has been slow and hampered by issues of inconsistency. Recent advances in the tools available for analysis-assaying transcription, sequence variation, and epigenetic marks on a genome-wide scale-have substantially altered this landscape. Applications of such approaches are consistent with heterogeneity at the level of causation and specify patterns of commonality with a wide range of alternative disease traits. Looking beyond the individual as the unit of study, advances in technology have also fostered comprehensive analysis of the human microbiome and its varied roles in health and disease. In this article, we consider the implications of these technological advances for our current understanding of the genetics and genomics of asthma.}, } @article {pmid30159882, year = {2018}, author = {Skelly, E and Kapellas, K and Cooper, A and Weyrich, LS}, title = {Consequences of colonialism: A microbial perspective to contemporary Indigenous health.}, journal = {American journal of physical anthropology}, volume = {167}, number = {2}, pages = {423-437}, doi = {10.1002/ajpa.23637}, pmid = {30159882}, issn = {1096-8644}, support = {DE150101574//Australian Research Council/ ; }, abstract = {Nearly all Indigenous populations today suffer from worse health than their non-Indigenous counterparts, and despite interventions against known factors, this health "gap" has not improved. The human microbiome-the beneficial, diverse microbial communities that live on and within the human body-is a crucial component in developing and maintaining normal physiological health. Disrupting this ecosystem has repercussions for microbial functionality, and thus, human health. In this article, we propose that modern-day Indigenous population health may suffer from disrupted microbial ecosystems as a consequence of historical colonialism. Colonialism may have interrupted the established relationships between the environment, traditional lifeways, and microbiomes, altering the Indigenous microbiome with detrimental health consequences.}, } @article {pmid30155556, year = {2018}, author = {Ma, ZS}, title = {Sketching the Human Microbiome Biogeography with DAR (Diversity-Area Relationship) Profiles.}, journal = {Microbial ecology}, volume = {}, number = {}, pages = {}, doi = {10.1007/s00248-018-1245-6}, pmid = {30155556}, issn = {1432-184X}, abstract = {SAR (species area relationship) is a classic ecological theory that has been extensively investigated and applied in the studies of global biogeography and biodiversity conservation in macro-ecology. It has also found important applications in microbial ecology in recent years thanks to the breakthroughs in metagenomic sequencing technology. Nevertheless, SAR has a serious limitation for practical applications-ignoring the species abundance and treating all species as equally abundant. This study aims to explore the biogeography discoveries of human microbiome over 18 sites of 5 major microbiome habitats, establish the baseline DAR (diversity-area scaling relationship) parameters, and perform comparisons with the classic SAR. The extension from SAR to DAR by adopting the Hill numbers as diversity measures not only overcomes the previously mentioned flaw of SAR but also allows for obtaining a series of important findings on the human microbiome biodiversity and biogeography. Specifically, two types of DAR models were built, the traditional power law (PL) and power law with exponential cutoff (PLEC), using comprehensive datasets from the HMP (human microbiome project). Furthermore, the biogeography "maps" for 18 human microbiome sites using their DAR profiles for assessing and predicting the diversity scaling across individuals, PDO profiles (pair-wise diversity overlap) for measuring diversity overlap (similarity), and MAD profile (for predicting the maximal accrual diversity in a population) were sketched out. The baseline biogeography maps for the healthy human microbiome diversity can offer guidelines for conserving human microbiome diversity and investigating the health implications of the human microbiome diversity and heterogeneity.}, } @article {pmid30154777, year = {2018}, author = {Westerik, N and Reid, G and Sybesma, W and Kort, R}, title = {The Probiotic Lactobacillus rhamnosus for Alleviation of Helicobacter pylori-Associated Gastric Pathology in East Africa.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {1873}, doi = {10.3389/fmicb.2018.01873}, pmid = {30154777}, issn = {1664-302X}, abstract = {The probiotic Lactobacillus rhamnosus GG (LGG) can play a role in establishing a harmless relationship with Helicobacter pylori and reduce gastric pathology in East African populations. H. pylori has the ability to inhabit the surface of the mucous layer of the human stomach and duodenum. In the developing world, an estimated 51% of the population is carrier of H. pylori, while in some Western countries these numbers dropped below 20%, which is probably associated with improved sanitation and smaller family sizes. Colonization by H. pylori can be followed by inflammation of the gastric mucus layer, and is a risk factor in the development of atrophic gastritis, peptic ulcers and gastric cancer. Notwithstanding the higher prevalence of H. pylori carriers in developing countries, no equal overall increase in gastric pathology is found. This has been attributed to a less pro-inflammatory immune response to H. pylori in African compared to Caucasian populations. In addition, a relatively low exposure to other risk factors in certain African populations may play a role, including the use of non-steroidal anti-inflammatory drugs, smoking, and diets without certain protective factors. A novel approach to the reduction of H. pylori associated gastric pathology is found in the administration of the probiotic bacterium Lactobacillus rhamnosus yoba 2012 (LRY), the generic variant of LGG. This gastro-intestinal isolate inhibits H. pylori by competition for substrate and binding sites as well as production of antimicrobial compounds such as lactic acid. In addition, it attenuates the host's H. pylori-induced apoptosis and inflammation responses and stimulates angiogenesis in the gastric and duodenal epithelium. The probiotic LRY is not able to eradicate H. pylori completely, but its co-supplementation in antibiotic eradication therapy has been shown to relieve side effects of this therapy. In Uganda, unlike other African countries, gastric pathology is relatively common, presumably resulting from the lack of dietary protective factors in the traditional diet. Supplementation with LRY through local production of probiotic yogurt, could be a solution to establish a harmless relationship with H. pylori and reduce gastric pathology and subsequent eradication therapy treatment.}, } @article {pmid30154767, year = {2018}, author = {Kho, ZY and Lal, SK}, title = {The Human Gut Microbiome - A Potential Controller of Wellness and Disease.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {1835}, doi = {10.3389/fmicb.2018.01835}, pmid = {30154767}, issn = {1664-302X}, abstract = {Interest toward the human microbiome, particularly gut microbiome has flourished in recent decades owing to the rapidly advancing sequence-based screening and humanized gnotobiotic model in interrogating the dynamic operations of commensal microbiota. Although this field is still at a very preliminary stage, whereby the functional properties of the complex gut microbiome remain less understood, several promising findings have been documented and exhibit great potential toward revolutionizing disease etiology and medical treatments. In this review, the interactions between gut microbiota and the host have been focused on, to provide an overview of the role of gut microbiota and their unique metabolites in conferring host protection against invading pathogen, regulation of diverse host physiological functions including metabolism, development and homeostasis of immunity and the nervous system. We elaborate on how gut microbial imbalance (dysbiosis) may lead to dysfunction of host machineries, thereby contributing to pathogenesis and/or progression toward a broad spectrum of diseases. Some of the most notable diseases namely Clostridium difficile infection (infectious disease), inflammatory bowel disease (intestinal immune-mediated disease), celiac disease (multisystemic autoimmune disorder), obesity (metabolic disease), colorectal cancer, and autism spectrum disorder (neuropsychiatric disorder) have been discussed and delineated along with recent findings. Novel therapies derived from microbiome studies such as fecal microbiota transplantation, probiotic and prebiotics to target associated diseases have been reviewed to introduce the idea of how certain disease symptoms can be ameliorated through dysbiosis correction, thus revealing a new scientific approach toward disease treatment. Toward the end of this review, several research gaps and limitations have been described along with suggested future studies to overcome the current research lacunae. Despite the ongoing debate on whether gut microbiome plays a role in the above-mentioned diseases, we have in this review, gathered evidence showing a potentially far more complex link beyond the unidirectional cause-and-effect relationship between them.}, } @article {pmid30150778, year = {2018}, author = {Xu, W and Luo, Z and Alekseyenko, AV and Martin, L and Wan, Z and Ling, B and Qin, Z and Heath, SL and Maas, K and Cong, X and Jiang, W}, title = {Distinct systemic microbiome and microbial translocation are associated with plasma level of anti-CD4 autoantibody in HIV infection.}, journal = {Scientific reports}, volume = {8}, number = {1}, pages = {12863}, doi = {10.1038/s41598-018-31116-y}, pmid = {30150778}, issn = {2045-2322}, support = {P30 AI027767/AI/NIAID NIH HHS/United States ; U54 CA210962/CA/NCI NIH HHS/United States ; R01 AI091526/AI/NIAID NIH HHS/United States ; R01 AI128864/AI/NIAID NIH HHS/United States ; U54 GM104940/GM/NIGMS NIH HHS/United States ; R01 CA228166/CA/NCI NIH HHS/United States ; R01 LM012517/LM/NLM NIH HHS/United States ; R01 AI093307/AI/NIAID NIH HHS/United States ; P50 AR070591/AR/NIAMS NIH HHS/United States ; K23 NR014674/NR/NINR NIH HHS/United States ; R01 CA164964/CA/NCI NIH HHS/United States ; R01 NR016928/NR/NINR NIH HHS/United States ; }, abstract = {Microbial signals have been linked to autoantibody induction. Recently, we found that purified anti-CD4 autoantibodies from the plasma of chronic HIV-1-infected patients under viral-suppressed antiretroviral therapy (ART) play a pathologic role in poor CD4+ T cell recovery. The purpose of the study was to investigate the association of systemic microbiome and anti-CD4 autoantibody production in HIV. Plasma microbiome from 12 healthy controls and 22 HIV-infected subjects under viral-suppressed ART were analyzed by MiSeq sequencing. Plasma level of autoantibodies and microbial translocation (LPS, total bacterial 16S rDNA, soluble CD14, and LPS binding protein) were analyzed by ELISA, limulus amebocyte assay, and qPCR. We found that plasma level of anti-CD4 IgGs but not anti-CD8 IgGs was increased in HIV+ subjects compared to healthy controls. HIV+ subjects with plasma anti-CD4 IgG > 50 ng/mL (high) had reduced microbial diversity compared to HIV+ subjects with anti-CD4 IgG ≤ 50 ng/mL (low). Moreover, plasma anti-CD4 IgG level was associated with elevated microbial translocation and reduced microbial diversity in HIV+ subjects. The Alphaproteobacteria class was significantly enriched in HIV+ subjects with low anti-CD4 IgG compared to patients with high anti-CD4 IgG even after controlling for false discovery rate (FDR). The microbial components were different from the phylum to genus level in HIV+ subjects with high anti-CD4 IgGs compared to the other two groups, but these differences were not significant after controlling for FDR. These results suggest that systemic microbial translocation and microbiome may associate with anti-CD4 autoantibody production in ART-treated HIV disease.}, } @article {pmid30146515, year = {2018}, author = {Suda, W and Ogata, Y and Nishijima, S}, title = {[Analysis of human microbiome using NGS.].}, journal = {Clinical calcium}, volume = {28}, number = {9}, pages = {1274-1281}, doi = {CliCa180912741281}, pmid = {30146515}, issn = {0917-5857}, abstract = {Recently, next generation sequencers(NGS)became prevalent and enable us possible to comprehensively analyze the entire human microbiome community structures including difficult-to-culture microbes. In this review, we introduce the NGS-based analytical methods of human microbiome, called "meta-16S analysis" and "metagenomic analysis", then show several fundamental data basing these analyses. Furthermore, we also introduce the importance of database improvement used for analysis and the DNA preparation method from human samples.}, } @article {pmid30144429, year = {2018}, author = {Friedman, ES and Li, Y and Shen, TD and Jiang, J and Chau, L and Adorini, L and Babakhani, F and Edwards, J and Shapiro, D and Zhao, C and Carr, RM and Bittinger, K and Li, H and Wu, GD}, title = {FXR-Dependent Modulation of the Human Small Intestinal Microbiome by the Bile Acid Derivative Obeticholic Acid.}, journal = {Gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.1053/j.gastro.2018.08.022}, pmid = {30144429}, issn = {1528-0012}, support = {R01 AA026302/AA/NIAAA NIH HHS/United States ; R01 GM123056/GM/NIGMS NIH HHS/United States ; K08 AA021424/AA/NIAAA NIH HHS/United States ; P30 DK050306/DK/NIDDK NIH HHS/United States ; P30 DK019525/DK/NIDDK NIH HHS/United States ; }, abstract = {BACKGROUND & AIMS: Intestinal bacteria can modify the composition of bile acids and bile acids, which are regulated by the farnesoid X receptor (FXR), affect the survival and growth of gut bacteria. We studied the effects of obeticholic acid (OCA), a bile acid analog and FXR agonist, on the intestinal microbiomes of humans and mice.

METHODS: We performed a phase 1 study in 24 healthy volunteers given OCA (5 mg, 10 mg, or 25 mg per day, for 17 days). Fecal and plasma specimens were collected at baseline (day 0) and on days 17 (end of dosing) and 37 (end of study). The fecal specimens were analyzed by shotgun metagenomic sequencing. A Uniref90 high stringency genomic analysis was used to assign specific genes to the taxonomic signature of bacteria whose abundance was associated with OCA. Male C57BL/6 mice were gavaged daily with water, vehicle, or OCA (10 mg/kg) for 2 weeks. Small intestine luminal contents were collected by flushing with saline and fecal pellets were collected at baseline and day 14. Mouse samples were analyzed by 16S tagged sequencing. Culture experiments were performed to determine taxonomic-specific effects of bile acids and OCA on bacterial growth.

RESULTS: Suppression of endogenous bile acid synthesis by OCA in subjects led to a reversible induction of Gram-positive bacteria that are found in the small intestine and are components of diet and the oral microbiota. We found that bile acids reduced proliferation of these bacteria in minimum inhibitory concentration assays. In these organisms, there was an increase in the representation of microbial genomic pathways involved in DNA synthesis and amino acid metabolism with OCA treatment of subjects. Consistent with these findings, mice fed OCA had reduced endogenous bile acid levels and an increased proportion of Firmicutes, specifically in the small intestine, compared to mice fed water or vehicle.

CONCLUSIONS: In studying the effects of OCA in humans and mice, we found evidence for interactions between bile acids and features of the small intestinal microbiome. These findings indicate that FXR activation alters the intestinal microbiota and could provide opportunities for microbiome biomarker discovery or new approaches to engineering the human microbiome.

CLINICAL TRIAL INFORMATION: ClinicalTrials.gov no: NCT01933503.}, } @article {pmid30135504, year = {2018}, author = {Hoen, AG and Madan, JC and Li, Z and Coker, M and Lundgren, SN and Morrison, HG and Palys, T and Jackson, BP and Sogin, ML and Cottingham, KL and Karagas, MR}, title = {Sex-specific associations of infants' gut microbiome with arsenic exposure in a US population.}, journal = {Scientific reports}, volume = {8}, number = {1}, pages = {12627}, doi = {10.1038/s41598-018-30581-9}, pmid = {30135504}, issn = {2045-2322}, support = {RD-83459901//U.S. Environmental Protection Agency (EPA)/ ; P01ES022832//U.S. Department of Health & Human Services | NIH | National Institute of Environmental Health Sciences (NIEHS)/ ; R01LM012723//U.S. Department of Health & Human Services | NIH | U.S. National Library of Medicine (NLM)/ ; R01 GM123014/GM/NIGMS NIH HHS/United States ; P20GM104416//U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)/ ; R01 LM012723/LM/NLM NIH HHS/United States ; K01 LM011985/LM/NLM NIH HHS/United States ; RD-83544201//U.S. Environmental Protection Agency (EPA)/ ; P20 ES018175/ES/NIEHS NIH HHS/United States ; R01GM123014//U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)/ ; P01 ES022832/ES/NIEHS NIH HHS/United States ; P20 GM104416/GM/NIGMS NIH HHS/United States ; }, abstract = {Arsenic is a ubiquitous environmental toxicant with antimicrobial properties that can be found in food and drinking water. The influence of arsenic exposure on the composition of the human microbiome in US populations remains unknown, particularly during the vulnerable infant period. We investigated the relationship between arsenic exposure and gut microbiome composition in 204 infants prospectively followed as part of the New Hampshire Birth Cohort Study. Infant urine was analyzed for total arsenic concentration using inductively coupled plasma mass spectrometry. Stool microbiome composition was determined using sequencing of the bacterial 16S rRNA gene. Infant urinary arsenic related to gut microbiome composition at 6 weeks of life (p = 0.05, adjusted for infant feeding type and urine specific gravity). Eight genera, six within the phylum Firmicutes, were enriched with higher arsenic exposure. Fifteen genera were negatively associated with urinary arsenic concentration, including Bacteroides and Bifidobacterium. Upon stratification by both sex and feeding method, we found detectable associations among formula-fed males (p = 0.008), but not other groups (p > 0.05 for formula-fed females and for breastfed males and females). Our findings from a US population indicate that even moderate arsenic exposure may have meaningful, sex-specific effects on the gut microbiome during a critical window of infant development.}, } @article {pmid30131772, year = {2018}, author = {Ma, Z and Li, L and Li, W}, title = {Assessing and Interpreting the Within-Body Biogeography of Human Microbiome Diversity.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {1619}, doi = {10.3389/fmicb.2018.01619}, pmid = {30131772}, issn = {1664-302X}, abstract = {A human body hosts a relatively independent microbiome including five major regional biomes (i.e., airway, oral, gut, skin, and urogenital). Each of them may possess different regional characteristics with important implications to our health and diseases (i.e., so-termed microbiome associated diseases). Nevertheless, these regional microbiomes are connected with each other through diffusions and migrations. Here, we investigate the within-body (intra-individual) distribution feature of microbiome diversity via diversity area relationship (DAR) modeling, which, to the best of our knowledge, has not been systematically studied previously. We utilized the Hill numbers for measuring alpha and beta-diversities and built 1,200 within-body DAR models with to date the most comprehensive human microbiome datasets of 18 sites from the human microbiome project (HMP) cohort. We established the intra-DAR profile (z-q pattern: the diversity scaling parameter z of the power law (PL) at diversity order q = 0-3), intra-PDO (pair-wise diversity overlap) profile (g-q), and intra-MAD (maximal accrual diversity) profile (Dmax-q) for the within-body biogeography of the human microbiome. These profiles constitute the "maps" of the within-body biogeography, and offer important insights on the within-body distribution of the human microbiome. Furthermore, we investigated the heterogeneity among individuals in their biogeography parameters and found that there is not an "average Joe" that can represent majority of individuals in a cohort or population. For example, we found that most individuals in the HMP cohort have relatively lower maximal accrual diversity (MAD) or in the "long tail" of the so-termed power law distribution. In the meantime, there are a small number of individuals in the cohort who possess disproportionally higher MAD values. These findings may have important implications for personalized medicine of the human microbiome associated diseases in practice, besides their theoretical significance in microbiome research such as establishing the baseline for the conservation of human microbiome.}, } @article {pmid30129129, year = {2018}, author = {Heerema-McKenney, A}, title = {Defense and infection of the human placenta.}, journal = {APMIS : acta pathologica, microbiologica, et immunologica Scandinavica}, volume = {126}, number = {7}, pages = {570-588}, doi = {10.1111/apm.12847}, pmid = {30129129}, issn = {1600-0463}, mesh = {Communicable Diseases/*pathology ; Female ; Humans ; Placenta/*immunology/*pathology ; Placenta Diseases/*pathology ; Pregnancy ; Pregnancy Complications, Infectious/*pathology ; }, abstract = {The placenta functions as a shield against infection of the fetus. The innate and adaptive immune defenses of the developing fetus are poorly equipped to fight infections. Infection by bacteria, viruses, and protozoa may cause infertility, spontaneous abortion, stillbirth, growth retardation, anomalies of development, premature delivery, neonatal morbidity, and mortality. However, appreciation of the human microbiome and host cell-microbe interactions must be taken into consideration as we try to determine what interactions are pathologic. Infection is typically recognized histologically by the presence of inflammation. Yet, several factors make comparison of the placenta to other human organs difficult. The placenta comprises tissues from two persons, complicating the role of the immune system. The placenta is a temporary organ. It must be eventually expelled; the processes leading to partuition involve maternal inflammation. What is normal or pathologic may be a function of timing or extent of the process. We now must consider whether bacteria, and even some viruses, are useful commensals or pathogens. Still, recognizing infection of the placenta is one of the most important contributions placental pathologic examination can give to care of the mother and neonate. This review provides a brief overview of placental defense against infection, consideration of the placental microbiome, routes of infection, and the histopathology of amniotic fluid infection and TORCH infections.}, } @article {pmid30129002, year = {2018}, author = {Lin, J and Kimura, BY and Oikarinen, S and Nykter, M}, title = {Bioinformatics Assembling and Assessment of Novel Coxsackievirus B1 Genome.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {1838}, number = {}, pages = {261-272}, doi = {10.1007/978-1-4939-8682-8_18}, pmid = {30129002}, issn = {1940-6029}, abstract = {The human microbiome project via application of metagenomic next-generation sequencing techniques has found surprising large and diverse amounts of microbial sequences across different body sites. There is a wave of investigators studying autoimmune related diseases designing from birth case and control studies to elucidate microbial associations and potential direct triggers. Sequencing analysis, considered big data as it typically includes millions of reads, is challenging but particularly demanding and complex is virome profiling due to its lack of pan-viral genomic signature. Impressively thousands of virus complete genomes have been deposited and these high-quality references are core components of virus profiling pipelines and databases. Still it is commonly known that most viral sequences do not map to known viruses. Moreover human viruses, particularly RNA groups, are notoriously heterogeneous due to high mutation rates. Here, we present the related assembling challenges and a series of bioinformatics steps that were applied in the construction of the complete consensus genome of a novel clinical isolate of Coxsackievirus B1. We further demonstrate our effort in calling mutations between prototype Coxsackievirus B1 sequence from GenBank and serial clinical isolate genome grown in cell culture.}, } @article {pmid30124405, year = {2018}, author = {Dubourg, G and Baron, S and Cadoret, F and Couderc, C and Fournier, PE and Lagier, JC and Raoult, D}, title = {From Culturomics to Clinical Microbiology and Forward.}, journal = {Emerging infectious diseases}, volume = {24}, number = {9}, pages = {1683-1690}, doi = {10.3201/eid2409.170995}, pmid = {30124405}, issn = {1080-6059}, abstract = {Culturomics has permitted discovery of hundreds of new bacterial species isolated from the human microbiome. Profiles generated by using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry have been added to the mass spectrometer database used in clinical microbiology laboratories. We retrospectively collected raw data from MALDI-TOF mass spectrometry used routinely in our laboratory in Marseille, France, during January 2012-March 2018 and analyzed 16S rDNA sequencing results from misidentified strains. During the study period, 744 species were identified from clinical specimens, of which 21 were species first isolated from culturomics. This collection involved 105 clinical specimens, accounting for 98 patients. In 64 cases, isolation of the bacteria was considered clinically relevant. MALDI-TOF mass spectrometry was able to identify the species in 95.2% of the 105 specimens. While contributing to the extension of the bacterial repertoire associated with humans, culturomics studies also enlarge the spectrum of prokaryotes involved in infectious diseases.}, } @article {pmid30111623, year = {2018}, author = {Bisanz, JE and Spanogiannopoulos, P and Pieper, LM and Bustion, AE and Turnbaugh, PJ}, title = {How to determine the role of the microbiome in drug disposition.}, journal = {Drug metabolism and disposition: the biological fate of chemicals}, volume = {}, number = {}, pages = {}, doi = {10.1124/dmd.118.083402}, pmid = {30111623}, issn = {1521-009X}, abstract = {With a paradigm shift occurring in health care towards personalized and precision medicine, understanding the numerous environmental factors that impact drug disposition is of paramount importance. The highly diverse and variant nature of the human microbiome is now recognized as a factor driving inter-individual variation in therapeutic outcomes. The purpose of this review is to provide a practical guide on methodology that can be applied to study the effects of microbes on the absorption, distribution, metabolism, and excretion of drugs. We also highlight recent examples of how these methods have been successfully applied to help build the basis for researching the intersection of microbiome and pharmacology. While in vitro and in vivo preclinical models are highlighted, these methods are also relevant in late-phase drug development or even as a part of routine after-market surveillance. These approaches will aid in filling major knowledge gaps for both current and upcoming therapeutics with the long-term goal of achieving a new type of knowledge-based medicine that integrates data on the host and the microbiome.}, } @article {pmid30110974, year = {2018}, author = {Fernández, MF and Reina-Pérez, I and Astorga, JM and Rodríguez-Carrillo, A and Plaza-Díaz, J and Fontana, L}, title = {Breast Cancer and Its Relationship with the Microbiota.}, journal = {International journal of environmental research and public health}, volume = {15}, number = {8}, pages = {}, doi = {10.3390/ijerph15081747}, pmid = {30110974}, issn = {1660-4601}, abstract = {The microorganisms that live symbiotically in human beings are increasingly recognized as important players in health and disease. The largest collection of these microorganisms is found in the gastrointestinal tract. Microbial composition reflects both genetic and lifestyle variables of the host. This microbiota is in a dynamic balance with the host, exerting local and distant effects. Microbial perturbation (dysbiosis) could contribute to the risk of developing health problems. Various bacterial genes capable of producing estrogen-metabolizing enzymes have been identified. Accordingly, gut microbiota is capable of modulating estrogen serum levels. Conversely, estrogen-like compounds may promote the proliferation of certain species of bacteria. Therefore, a crosstalk between microbiota and both endogenous hormones and estrogen-like compounds might synergize to provide protection from disease but also to increase the risk of developing hormone-related diseases. Recent research suggests that the microbiota of women with breast cancer differs from that of healthy women, indicating that certain bacteria may be associated with cancer development and with different responses to therapy. In this review, we discuss recent knowledge about the microbiome and breast cancer, identifying specific characteristics of the human microbiome that may serve to develop novel approaches for risk assessment, prevention and treatment for this disease.}, } @article {pmid30108246, year = {2018}, author = {Bučević Popović, V and Šitum, M and Chow, CT and Chan, LS and Roje, B and Terzić, J}, title = {The urinary microbiome associated with bladder cancer.}, journal = {Scientific reports}, volume = {8}, number = {1}, pages = {12157}, doi = {10.1038/s41598-018-29054-w}, pmid = {30108246}, issn = {2045-2322}, support = {IP-2014-09-1904//Hrvatska Zaklada za Znanost (Croatian Science Foundation)/ ; }, abstract = {Recent findings suggest that human microbiome can influence the development of cancer, but the role of microorganisms in bladder cancer pathogenesis has not been explored yet. The aim of this study was to characterize and compare the urinary microbiome of bladder cancer patients with those of healthy controls. Bacterial communities present in urine specimens collected from 12 male patients diagnosed with bladder cancer, and from 11 healthy, age-matched individuals were analysed using 16S sequencing. Our results show that the most abundant phylum in both groups was Firmicutes, followed by Actinobacteria, Bacteroidetes and Proteobacteria. While microbial diversity and overall microbiome composition were not significantly different between groups, we could identify operational taxonomic units (OTUs) that were more abundant in either group. Among those that were significantly enriched in the bladder cancer group, we identified an OTU belonging to genus Fusobacterium, a possible protumorigenic pathogen. In an independent sample of 42 bladder cancer tissues, 11 had Fusobacterium nucleatum sequences detected by PCR. Three OTUs from genera Veillonella, Streptococcus and Corynebacterium were more abundant in healthy urines. However, due to the limited number of participants additional studies are needed to determine if urinary microbiome is associated with bladder cancer.}, } @article {pmid30099552, year = {2018}, author = {Bastiaanssen, TFS and Cowan, CSM and Claesson, MJ and Dinan, TG and Cryan, JF}, title = {Making Sense of… the Microbiome in Psychiatry.}, journal = {The international journal of neuropsychopharmacology}, volume = {}, number = {}, pages = {}, doi = {10.1093/ijnp/pyy067}, pmid = {30099552}, issn = {1469-5111}, abstract = {Microorganisms can be found almost anywhere, including in and on the human body. The collection of microorganisms associated with a certain location is called a microbiota with its collective genetic material referred to as the microbiome. The largest population of microorganisms on the human body resides in the gastrointestinal tract thus it is not surprising that most investigated human microbiome is the human gut microbiome. On average, the gut hosts microbes from more than 60 genera and contains more cells than the human body. The human gut microbiome has been shown to influence many aspects of host health including more recently the brain.Several modes of interaction between the gut and the brain have been discovered, including via the synthesis of metabolites and neurotransmitters, activation of the vagus nerve and activation of the immune system. A growing body of work is implicating the microbiome in a variety of psychological processes and neuropsychiatric disorders. These include mood and anxiety disorders, neurodevelopmental disorders such as autism spectrum disorder and schizophrenia, and even neurodegenerative disorders such as Alzheimer's and Parkinson's Disease. Moreover, it is probable that most psychotropic medications have an impact on the microbiome.Here, an overview will be provided for the bidirectional role of the microbiome in brain health, age-associated cognitive decline, neurological and psychiatric disorders. Furthermore, a primer on the common microbiological and bioinformatics techniques used to interrogate the microbiome will be provided. This review is meant to equip the reader with a primer to this exciting research area which is permeating all areas of biological psychiatry research.}, } @article {pmid30098679, year = {2018}, author = {Kroon, SJ and Ravel, J and Huston, WM}, title = {Cervicovaginal microbiota, women's health, and reproductive outcomes.}, journal = {Fertility and sterility}, volume = {110}, number = {3}, pages = {327-336}, doi = {10.1016/j.fertnstert.2018.06.036}, pmid = {30098679}, issn = {1556-5653}, abstract = {The human microbiome project has shown a remarkable diversity of microbial ecology within the human body. The vaginal microbiota is unique in that in many women it is most often dominated by Lactobacillus species. However, in some women it lacks Lactobacillus spp. and is comprised of a wide array of strict and facultative anaerobes, a state that broadly correlates with increased risk for infection, disease, and poor reproductive and obstetric outcomes. Interestingly, the level of protection against infection can also vary by species and strains of Lactobacillus, and some species although dominant are not always optimal. This factors into the risk of contracting sexually transmitted infections and possibly influences the occurrence of resultant adverse reproductive outcomes such as tubal factor infertility. The composition and function of the vaginal microbiota appear to play an important role in pregnancy and fertility treatment outcomes and future research in this field will shed further translational mechanistic understanding onto the interplay of the vaginal microbiota with women's health and reproduction.}, } @article {pmid30082394, year = {2018}, author = {Shrivastava, A and Patel, VK and Tang, Y and Yost, SC and Dewhirst, FE and Berg, HC}, title = {Cargo transport shapes the spatial organization of a microbial community.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {34}, pages = {8633-8638}, doi = {10.1073/pnas.1808966115}, pmid = {30082394}, issn = {1091-6490}, support = {K99 DE026826/DE/NIDCR NIH HHS/United States ; R01 AI016478/AI/NIAID NIH HHS/United States ; }, mesh = {Capnocytophaga/*physiology ; Humans ; Microbial Consortia/*physiology ; Microbiota/*physiology ; Mouth/*microbiology ; }, abstract = {The human microbiome is an assemblage of diverse bacteria that interact with one another to form communities. Bacteria in a given community are arranged in a 3D matrix with many degrees of freedom. Snapshots of the community display well-defined structures, but the steps required for their assembly are not understood. Here, we show that this construction is carried out with the help of gliding bacteria. Gliding is defined as the motion of cells over a solid or semisolid surface without the necessity of growth or the aid of pili or flagella. Genomic analysis suggests that gliding bacteria are present in human microbial communities. We focus on Capnocytophaga gingivalis, which is present in abundance in the human oral microbiome. Tracking of fluorescently labeled single cells and of gas bubbles carried by fluid flow shows that swarms of C. gingivalis are layered, with cells in the upper layers moving more rapidly than those in the lower layers. Thus, cells also glide on top of one another. Cells of nonmotile bacterial species attach to the surface of C. gingivalis and are propelled as cargo. The cargo cell moves along the length of a C. gingivalis cell, looping from one pole to the other. Multicolor fluorescent spectral imaging of cells of different live but nonmotile bacterial species reveals their long-range transport in a polymicrobial community. A swarm of C. gingivalis transports some nonmotile bacterial species more efficiently than others and helps to shape the spatial organization of a polymicrobial community.}, } @article {pmid30078138, year = {2018}, author = {Martin, TC and Visconti, A and Spector, TD and Falchi, M}, title = {Conducting metagenomic studies in microbiology and clinical research.}, journal = {Applied microbiology and biotechnology}, volume = {102}, number = {20}, pages = {8629-8646}, doi = {10.1007/s00253-018-9209-9}, pmid = {30078138}, issn = {1432-0614}, support = {//Wellcome Trust/United Kingdom ; }, abstract = {Owing to the increased cost-effectiveness of high-throughput technologies, the number of studies focusing on the human microbiome and its connections to human health and disease has recently surged. However, best practices in microbiology and clinical research have yet to be clearly established. Here, we present an overview of the challenges and opportunities involved in conducting a metagenomic study, with a particular focus on data processing and analytical methods.}, } @article {pmid30074108, year = {2018}, author = {Bicknell, B and Liebert, A and Johnstone, D and Kiat, H}, title = {Photobiomodulation of the microbiome: implications for metabolic and inflammatory diseases.}, journal = {Lasers in medical science}, volume = {}, number = {}, pages = {}, doi = {10.1007/s10103-018-2594-6}, pmid = {30074108}, issn = {1435-604X}, abstract = {The human microbiome is intimately associated with human health, with a role in obesity, metabolic diseases such as type 2 diabetes, and divergent diseases such as cardiovascular and neurodegenerative diseases. The microbiome can be changed by diet, probiotics, and faecal transplants, which has flow-on effects to health outcomes. Photobiomodulation has a therapeutic effect on inflammation and neurological disorders (amongst others) and has been reported to influence metabolic disorders and obesity. The aim of this study was to examine the possibility that PBM could influence the microbiome of mice. Mice had their abdomen irradiated with red (660 nm) or infrared (808 nm) low-level laser, either as single or multiple doses, over a 2-week period. Genomic DNA extracted from faecal pellets was pyrosequenced for the 16S rRNA gene. There was a significant (p < 0.05) difference in microbial diversity between PBM- and sham-treated mice. One genus of bacterium (Allobaculum) significantly increased (p < 0.001) after infrared (but not red light) PBM by day 14. Despite being a preliminary trial with small experimental numbers, we have demonstrated for the first time that PBM can alter microbiome diversity in healthy mice and increase numbers of Allobaculum, a bacterium associated with a healthy microbiome. This change is most probably a result of PBMt affecting the host, which in turn influenced the microbiome. If this is confirmed in humans, the possibility exists for PBMt to be used as an adjunct therapy in treatment of obesity and other lifestyle-related disorders, as well as cardiovascular and neurodegenerative diseases. The clinical implications of altering the microbiome using PBM warrants further investigation.}, } @article {pmid30071492, year = {2018}, author = {Hanssen, EN and Liland, KH and Gill, P and Snipen, L}, title = {Optimizing body fluid recognition from microbial taxonomic profiles.}, journal = {Forensic science international. Genetics}, volume = {37}, number = {}, pages = {13-20}, doi = {10.1016/j.fsigen.2018.07.012}, pmid = {30071492}, issn = {1878-0326}, abstract = {In forensics the DNA-profile is used to identify the person who left a biological trace, but information on body fluid can also be essential in the evidence evaluation process. Microbial composition data could potentially be used for body fluid recognition as an improved alternative to the currently used presumptive tests. We have developed a customized workflow for interpretation of bacterial 16S sequence data based on a model composed of Partial Least Squares (PLS) in combination with Linear Discriminant Analysis (LDA). Large data sets from the Human Microbiome Project (HMP) and the American Gut Project (AGP) were used to test different settings in order to optimize performance. From the initial cross-validation of body fluid recognition within the HMP data, the optimal overall accuracy was close to 98%. Sensitivity values for the fecal and oral samples were ≥0.99, followed by the vaginal samples with 0.98 and the skin and nasal samples with 0.96 and 0.81 respectively. Specificity values were high for all 5 categories, mostly >0.99. This optimal performance was achieved by using the following settings: Taxonomic profiles based on operational taxonomic units (OTUs) with 0.98 identity (OTU98), Aitchisons simplex transform with C = 1 pseudo-count and no regularization (r = 1) in the PLS step. Variable selection did not improve the performance further. To test for robustness across sequencing platforms, we also trained the classifier on HMP data and tested on the AGP data set. In this case, the standard OTU based approach showed moderately decline in accuracy. However, by using taxonomic profiles made by direct assignment of reads to a genus, we were able to nearly maintain the high accuracy levels. The optimal combination of settings was still used, except the taxonomic level being genus instead of OTU98. The performance may be improved even further by using higher resolution taxonomic bins.}, } @article {pmid30069974, year = {2018}, author = {Mert, I and Walther-Antonio, M and Mariani, A}, title = {Case for a role of the microbiome in gynecologic cancers: Clinician's perspective.}, journal = {The journal of obstetrics and gynaecology research}, volume = {44}, number = {9}, pages = {1693-1704}, doi = {10.1111/jog.13701}, pmid = {30069974}, issn = {1447-0756}, abstract = {In this review, we aimed to provide insight into the microbiome and its association with endometrial and ovarian cancer and their risk factors. We reviewed the literature focusing on the relationship between the microbiome and cancer, as well as the relationship between gynecologic diseases and cancers. The human body contains different kinds of microorganisms in various body parts, which is termed the microbiome. The number of microorganisms that live in and on the human body is greater than that of the human germ and somatic cells by 10-fold. The relationship between a human and their microbiome is complex; it is also one of the most important components of homeostasis. Impairment of microbiome-host homeostasis has been associated with obesity, several cancers, preterm labor, inflammatory and allergic conditions and neurodevelopmental disorders. Direct and strong causal relationships have been established for several cancers and microorganisms, such as gastric lymphoma and Helicobacter pylori infection. Interestingly, eradication of the infectious agents has also been shown to be therapeutic. The association between cancer and the microbiome, however, is more complicated than a 1 bacteria-1 cancer model, and a shift in a healthy microbiome can result in various cancers via inflammation, change in microenvironment or DNA-damaging toxins. The human microbiome is an integral part of homeostasis. Understanding the mechanisms that cause dysbiosis will enable us to elucidate the pathways that result in malignancy and investigate new treatment modalities.}, } @article {pmid30066739, year = {2018}, author = {Costa, AN and Costa, FMD and Campos, SV and Salles, RK and Athanazio, RA}, title = {The pulmonary microbiome: challenges of a new paradigm.}, journal = {Jornal brasileiro de pneumologia : publicacao oficial da Sociedade Brasileira de Pneumologia e Tisilogia}, volume = {}, number = {}, pages = {0}, doi = {10.1590/S1806-37562017000000209}, pmid = {30066739}, issn = {1806-3756}, abstract = {The study of the human microbiome-and, more recently, that of the respiratory system-by means of sophisticated molecular biology techniques, has revealed the immense diversity of microbial colonization in humans, in human health, and in various diseases. Apparently, contrary to what has been believed, there can be nonpathogenic colonization of the lungs by microorganisms such as bacteria, fungi, and viruses. Although this physiological lung microbiome presents low colony density, it presents high diversity. However, some pathological conditions lead to a loss of that diversity, with increasing concentrations of some bacterial genera, to the detriment of others. Although we possess qualitative knowledge of the bacteria present in the lungs in different states of health or disease, that knowledge has advanced to an understanding of the interaction of this microbiota with the local and systemic immune systems, through which it modulates the immune response. Given this intrinsic relationship between the microbiota and the lungs, studies have put forth new concepts about the pathophysiological mechanisms of homeostasis in the respiratory system and the potential dysbiosis in some diseases, such as cystic fibrosis, COPD, asthma, and interstitial lung disease. This departure from the paradigm regarding knowledge of the lung microbiota has made it imperative to improve understanding of the role of the microbiome, in order to identify possible therapeutic targets and to develop innovative clinical approaches. Through this new leap of knowledge, the results of preliminary studies could translate to benefits for our patients.}, } @article {pmid30058389, year = {2018}, author = {Greco, V and Piras, C and Pieroni, L and Ronci, M and Putignani, L and Roncada, P and Urbani, A}, title = {Applications of MALDI-TOF mass spectrometry in clinical proteomics.}, journal = {Expert review of proteomics}, volume = {15}, number = {8}, pages = {683-696}, doi = {10.1080/14789450.2018.1505510}, pmid = {30058389}, issn = {1744-8387}, abstract = {INTRODUCTION: The development of precision medicine requires advanced technologies to address the multifactorial disease stratification and to support personalized treatments. Among omics techniques, proteomics based on Mass Spectrometry (MS) is becoming increasingly relevant in clinical practice allowing a phenotypic characterization of the dynamic functional status of the organism. From this perspective, Matrix Assisted Laser Desorption Ionization Time of Flight (MALDI-TOF) MS is a suitable platform for providing a high-throughput support to clinics. Areas covered: This review aims to provide an updated overview of MALDI-TOF MS applications in clinical proteomics. The most relevant features of this analysis have been discussed, highlighting both pre-analytical and analytical factors that are crucial in proteomics studies. Particular emphasis is placed on biofluids proteomics for biomarkers discovery and on recent progresses in clinical microbiology, drug monitoring, and minimal residual disease (MRD). Expert commentary: Despite some analytical limitations, the latest technological advances together with the easiness of use, the low time and low cost consuming and the high throughput are making MALDI-TOF MS instruments very attractive for the clinical practice. These features offer a significant potential for the routine of the clinical laboratory and ultimately for personalized medicine.}, } @article {pmid30056862, year = {2018}, author = {Rosa, CP and Brancaglion, GA and Miyauchi-Tavares, TM and Corsetti, PP and de Almeida, LA}, title = {Antibiotic-induced dysbiosis effects on the murine gastrointestinal tract and their systemic repercussions.}, journal = {Life sciences}, volume = {207}, number = {}, pages = {480-491}, doi = {10.1016/j.lfs.2018.06.030}, pmid = {30056862}, issn = {1879-0631}, mesh = {Animals ; Anti-Bacterial Agents/*adverse effects ; Cytokines/metabolism ; Disease Models, Animal ; Dysbiosis/*drug therapy ; Fatty Acids, Volatile/chemistry ; Gastrointestinal Microbiome/*drug effects ; Gastrointestinal Tract/*drug effects/microbiology ; Homeostasis ; Humans ; Inflammation ; Mice ; T-Lymphocyte Subsets ; T-Lymphocytes/cytology ; }, abstract = {The gastrointestinal tract has become a focus of study recently. The crosstalk between microbiota, especially bacteria, and the intestinal mucosa has to be accurately balanced in order to maintain physiological homeostasis in the human body. This dynamic interaction results in different levels of short-chain fatty acids (SCFAs), IgA, and T cell lymphocyte subsets, which could lead the human body towards health or disease. The disruption of this microbiome characterises gut dysbiosis. Antibiotics are usually prescribed to fight against bacterial infection. They can also modulate the human microbiome, since it acts directly over organisational taxonomic units (OTUs) when taken orally. As a result, these pharmaceuticals enable gut dysbiosis and its systemic effects due to microbiome disturbance. Here, current data have been gathered from mice model experiments and epidemiological studies in an antibiotic-centred perspective. The presented data suggest the importance of translational studies in a murine model focusing on GIT homeostasis with bacterial groups since any changes to the GIT-microbiota have systemic repercussions in human health and disease.}, } @article {pmid30052903, year = {2018}, author = {Frey, AM and Ansbro, K and Kamble, NS and Pham, TK and Stafford, GP}, title = {Characterisation and pure culture of putative health-associated oral bacterium BU063 (Tannerella sp. HOT-286) reveals presence of a potentially novel glycosylated S-layer.}, journal = {FEMS microbiology letters}, volume = {365}, number = {17}, pages = {}, doi = {10.1093/femsle/fny180}, pmid = {30052903}, issn = {1574-6968}, abstract = {Tannerella HOT-286 (phylotype BU063) is a recently identified novel filamentous Gram-negative anaerobic oral bacterium cultured for the first time recently in co-culture with Propionibacterium acnes. In contrast to the related periodontal disease-associated pathobiont Tannerella forsythia, it is considered a putative health-associated bacterium. In this paper, we identified that this organism could be grown in pure culture if N-acetyl muramic acid (NAM) was provided in the media, although surprisingly the genetic basis of this phenomenon is not likely to be due to a lack of NAM synthesis genes. During further microbiological investigations, we showed for the first time that T. HOT-286 possesses a prominent extracellular S-layer with a novel morphology putatively made up of two proteins modified with an unknown glycan. These data further our knowledge of this poorly understood organism and genus that is an important part of the oral and human microbiome.}, } @article {pmid30052094, year = {2018}, author = {Laing, B and Barnett, MPG and Marlow, G and Nasef, NA and Ferguson, LR}, title = {An update on the role of gut microbiota in chronic inflammatory diseases, and potential therapeutic targets.}, journal = {Expert review of gastroenterology & hepatology}, volume = {}, number = {}, pages = {1-15}, doi = {10.1080/17474124.2018.1505497}, pmid = {30052094}, issn = {1747-4132}, abstract = {INTRODUCTION: The human microbiome plays a critical role in human health, having metabolic, protective, and trophic functions, depending upon its' exact composition. This composition is affected by a number of factors, including the genetic background of the individual, early life factors (including method of birth, length of breastfeeding) and nature of the diet and other environmental exposures (including cigarette smoking) and general life habits. It plays a key role in the control of inflammation, and in turn, its' composition is significantly influenced by inflammation. Areas covered: We consider metabolic, protective, and trophic functions of the microbiome and influences through the lifespan from post-partum effects, to diet later in life in healthy older adults, the effects of aging on both its' composition, and influence on health and potential therapeutic targets that may have anti-inflammatory effects. Expert commentary: The future will see the growth of more effective therapies targeting the microbiome particularly with respect to the use of specific nutrients and diets personalized to the individual.}, } @article {pmid30042747, year = {2018}, author = {Westerik, N and Kort, R and Sybesma, W and Reid, G}, title = {Lactobacillus rhamnosus Probiotic Food as a Tool for Empowerment Across the Value Chain in Africa.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {1501}, doi = {10.3389/fmicb.2018.01501}, pmid = {30042747}, issn = {1664-302X}, abstract = {Perhaps by serendipity, but Lactobacillus rhamnosus has emerged from the 1980s as the most researched probiotic species. The many attributes of the two main probiotic strains of the species, L. rhamnosus GG and GR-1, have made them suitable for applications to developing countries in Africa and beyond. Their use with a Streptococcus thermophilus starter strain C106, in the fermentation of milk, millet, and juices has provided a means to reach over 250,000 consumers of the first probiotic food on the continent. The social and economical implications for this translational research are significant, and especially pertinent for people living in poverty, with malnutrition and exposure to environmental toxins and infectious diseases including HIV and malaria. This example of probiotic applications illustrates the power of microbes in positively impacting the lives of women, men, and children, right across the food value chain.}, } @article {pmid30039798, year = {2018}, author = {Zhang, XS and Li, J and Krautkramer, KA and Badri, M and Battaglia, T and Borbet, TC and Koh, H and Ng, S and Sibley, RA and Li, Y and Pathmasiri, W and Jindal, S and Shields-Cutler, RR and Hillmann, B and Al-Ghalith, GA and Ruiz, VE and Livanos, A and van 't Wout, AB and Nagalingam, N and Rogers, AB and Sumner, SJ and Knights, D and Denu, JM and Li, H and Ruggles, KV and Bonneau, R and Williamson, RA and Rauch, M and Blaser, MJ}, title = {Antibiotic-induced acceleration of type 1 diabetes alters maturation of innate intestinal immunity.}, journal = {eLife}, volume = {7}, number = {}, pages = {}, doi = {10.7554/eLife.37816}, pmid = {30039798}, issn = {2050-084X}, support = {T35 DK007421/DK/NIDDK NIH HHS/United States ; R01 DK110014/DK/NIDDK NIH HHS/United States ; R01DK110014/NH/NIH HHS/United States ; T32 GM008692/GM/NIGMS NIH HHS/United States ; T32 GM007308/GM/NIGMS NIH HHS/United States ; 5T35DK007421/NH/NIH HHS/United States ; F30 DK108494/DK/NIDDK NIH HHS/United States ; R37GM059785/NH/NIH HHS/United States ; 15-A0-00-00-0039-29-01//Janssen Research and Development/International ; -33.17CVD01//Fondation Leducq/International ; R37 GM059785/GM/NIGMS NIH HHS/United States ; F30DK108494/NH/NIH HHS/United States ; 15-A0-00-00-0039-29-01//Janssen Labs London/International ; }, abstract = {The early-life intestinal microbiota plays a key role in shaping host immune system development. We found that a single early-life antibiotic course (1PAT) accelerated type 1 diabetes (T1D) development in male NOD mice. The single course had deep and persistent effects on the intestinal microbiome, leading to altered cecal, hepatic, and serum metabolites. The exposure elicited sex-specific effects on chromatin states in the ileum and liver and perturbed ileal gene expression, altering normal maturational patterns. The global signature changes included specific genes controlling both innate and adaptive immunity. Microbiome analysis revealed four taxa each that potentially protect against or accelerate T1D onset, that were linked in a network model to specific differences in ileal gene expression. This simplified animal model reveals multiple potential pathways to understand pathogenesis by which early-life gut microbiome perturbations alter a global suite of intestinal responses, contributing to the accelerated and enhanced T1D development.}, } @article {pmid30021103, year = {2018}, author = {Proal, AD and Marshall, TG}, title = {Re-framing the theory of autoimmunity in the era of the microbiome: persistent pathogens, autoantibodies, and molecular mimicry.}, journal = {Discovery medicine}, volume = {25}, number = {140}, pages = {299-308}, pmid = {30021103}, issn = {1944-7930}, abstract = {The theory of autoimmunity was developed at a time when the human body was regarded as largely sterile. Antibodies in patients with chronic inflammatory disease could consequently not be tied to persistent human pathogens. The concept of the "autoantibody" was created to reconcile this phenomenon. Today, however, the discovery of the human microbiome has revolutionized our understanding of human biology. Humans are superorganisms that harbor trillions of persistent microbial cells. Indeed, vast human microbiomes have been detected in human tissue and blood. These microbial ecosystems harbor thousands of newly identified bacteria, viruses, and other microorganisms -- most of which can act as pathogens under conditions of immunosuppression. The theory of autoimmunity must be revised to account for the human microbiome. Here, we propose a model in which "autoantibodies" are created in response to chronic, persistent microbiome pathogens. The structural homology (molecular mimicry) between pathogen and host proteins can result in "collateral damage" to surrounding human tissue. This calls for a paradigm shift in autoimmune disease treatment. Immunosuppressive medications palliate inflammatory symptoms at the expense of microbiome health and balance. In contrast, treatments that support the immune system in autoimmune disease could allow patients to target pathogens at the root of the disease process.}, } @article {pmid30019906, year = {2018}, author = {Wang, AY and Thuy-Boun, PS and Stupp, GS and Su, AI and Wolan, DW}, title = {Triflic Acid Treatment Enables LC-MS/MS Analysis of Insoluble Bacterial Biomass.}, journal = {Journal of proteome research}, volume = {17}, number = {9}, pages = {2978-2986}, doi = {10.1021/acs.jproteome.8b00166}, pmid = {30019906}, issn = {1535-3907}, abstract = {The lysis and extraction of soluble bacterial proteins from cells is a common practice for proteomics analyses, but insoluble bacterial biomasses are often left behind. Here, we show that with triflic acid treatment, the insoluble bacterial biomass of Gram- and Gram+ bacteria can be rendered soluble. We use LC-MS/MS shotgun proteomics to show that bacterial proteins in the soluble and insoluble postlysis fractions differ significantly. Additionally, in the case of Gram- Pseudomonas aeruginosa, triflic acid treatment enables the enrichment of cell-envelope-associated proteins. Finally, we apply triflic acid to a human microbiome sample to show that this treatment is robust and enables the identification of a new, complementary subset of proteins from a complex microbial mixture.}, } @article {pmid30017599, year = {2018}, author = {Chanyi, RM and Alzubaidi, R and Leung, EJY and Wilcox, HB and Brock, GB and Burton, JP}, title = {Inflatable Penile Prostheses Implantation: Does Antibiotic Exposure Matter?.}, journal = {Sexual medicine}, volume = {6}, number = {3}, pages = {248-254}, doi = {10.1016/j.esxm.2018.05.004}, pmid = {30017599}, issn = {2050-1161}, abstract = {BACKGROUND: Inflatable penile prosthetic (IPP) infections are unusual but carry high patient morbidity and healthcare costs.

AIM: To increase the bactericidal effect of IPP tubing material to prevent future bacterial infections and to determine whether this effect is time-dependent.

METHODS: A modified disk diffusion assay was developed to measure the zones of inhibition against Escherichia coli, Proteus mirabilis, Staphylococcus aureus, and Staphylococcus epidermidis when tubing was immersed in gentamycin, ampicillin, tetracycline, kanamycin, erythromycin, or ciprofloxacin. To further assess the efficacy of this approach, IPP tubing was exposed to ampicillin or ciprofloxacin for 30 seconds, 2 minutes, 10 minutes, or 60 minutes.

OUTCOMES: Bacterial zones of inhibition against IPP tubing material exposed to various treatments.

RESULTS: IPP tubing was more effective against Gram-positive bacteria (S aureus and S epidermidis) then Gram-negative bacteria (E coli and P mirabilis). Immersing IPP tubing material in ampicillin or ciprofloxacin increased bactericidal effect of tubing material against Gram-positive and Gram-negative bacteria, respectively. The observed inhibitory effect was time dependent.

CLINICAL TRANSLATION: Exposing IPP to a specific antimicrobial directly before implantation increases the bactericidal properties of the material, potentially decreasing the likelihood of infection.

STRENGTHS & LIMITATIONS: This study is limited in that it is in vitro experimentation observing the effect of a single strain of each bacterium. Although the strains used were clinically relevant, further analysis is required to determine whether these results were strain specific.

CONCLUSION: Immersing IPP material into an antibiotic solution, such as ampicillin or ciprofloxacin, increases the bactericidal properties and may aid in the prevention of infection. Chanyi RM, Alzubaidi R, Leung EJY, Wilcox HB, Brock GB, Burton JP. Inflatable Penile Prostheses Implantation: Does Antibiotic Exposure Matter? Sex Med 2018;6;248-254.}, } @article {pmid30015225, year = {2018}, author = {Schnorr, SL}, title = {Meanings, measurements, and musings on the significance of patterns in human microbiome variation.}, journal = {Current opinion in genetics & development}, volume = {53}, number = {}, pages = {43-52}, doi = {10.1016/j.gde.2018.06.014}, pmid = {30015225}, issn = {1879-0380}, abstract = {Variation of the human microbiome is a multidimensional value depending on the question of interest. Unlike traditional human genetics, which most often deals with variation at the level of genes or genetic sequences, microbiome variation may be most relevant at the functional level and can be interrogated a number of ways. Most common methods are marker gene metataxonomic surveys or shotgun metagenomic sequencing, however more direct indicators of microbial activity that are gaining popularity include metabolomic and metatranscriptomic surveys. With all these data and promise in human microbiome research, it requires that we reassess what is meant by variation of the human microbiome and how its significance impacts the ability of microbiome research to be informative on a range of topics from evolutionary theory to clinical outcomes. Learning from mistakes is essential to advancing the field, and new sophisticated analysis tools are helping to crystallize associations between microbiome variation and its drivers so that firm ground supports future explorations of mechanism. However, the body of current data suggests that these may be highly individualized due to the array of interactions between the host, the microbiome, and the environment. As a result, microbiome researchers need to be cognizant of population contexts and the limits these impose on conclusive outcomes.}, } @article {pmid30014852, year = {2018}, author = {Yao, L and Seaton, SC and Ndousse-Fetter, S and Adhikari, AA and DiBenedetto, N and Mina, AI and Banks, AS and Bry, L and Devlin, AS}, title = {A selective gut bacterial bile salt hydrolase alters host metabolism.}, journal = {eLife}, volume = {7}, number = {}, pages = {}, doi = {10.7554/eLife.37182}, pmid = {30014852}, issn = {2050-084X}, support = {Innovation Award//The Center for Microbiome Informatics and Therapeutics at MIT/ ; P60 DK020593/DK/NIDDK NIH HHS/United States ; P30 DK034854/DK/NIDDK NIH HHS/United States ; P30 DK020593/DK/NIDDK NIH HHS/United States ; Center for Microbiome Informatics and Therapeutics - Innovation Award//Massachusetts Institute of Technology/ ; Junior Faculty Award//Karin Grunebaum Cancer Research Foundation/ ; P30DK034854//National Institutes of Health/ ; NIH grant P30DK034854//The Harvard Digestive Diseases Center/ ; P30 CA006516/CA/NCI NIH HHS/United States ; U24 DK059637/DK/NIDDK NIH HHS/United States ; }, abstract = {The human gut microbiota impacts host metabolism and has been implicated in the pathophysiology of obesity and metabolic syndromes. However, defining the roles of specific microbial activities and metabolites on host phenotypes has proven challenging due to the complexity of the microbiome-host ecosystem. Here, we identify strains from the abundant gut bacterial phylum Bacteroidetes that display selective bile salt hydrolase (BSH) activity. Using isogenic strains of wild-type and BSH-deleted Bacteroides thetaiotaomicron, we selectively modulated the levels of the bile acid tauro-β-muricholic acid in monocolonized gnotobiotic mice. B. thetaiotaomicron BSH mutant-colonized mice displayed altered metabolism, including reduced weight gain and respiratory exchange ratios, as well as transcriptional changes in metabolic, circadian rhythm, and immune pathways in the gut and liver. Our results demonstrate that metabolites generated by a single microbial gene and enzymatic activity can profoundly alter host metabolism and gene expression at local and organism-level scales.}, } @article {pmid30014616, year = {2018}, author = {Rands, CM and Starikova, EV and Brüssow, H and Kriventseva, EV and Govorun, VM and Zdobnov, EM}, title = {ACI-1 beta-lactamase is widespread across human gut microbiomes in Negativicutes due to transposons harboured by tailed prophages.}, journal = {Environmental microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1111/1462-2920.14276}, pmid = {30014616}, issn = {1462-2920}, abstract = {Antibiotic resistance is increasing among pathogens, and the human microbiome contains a reservoir of antibiotic resistance genes. Acidaminococcus intestini is the first Negativicute bacterium (Gram-negative Firmicute) shown to be resistant to beta-lactam antibiotics. Resistance is conferred by the aci1 gene, but its evolutionary history and prevalence remain obscure. We discovered that ACI-1 proteins are phylogenetically distinct from beta-lactamases of Gram-positive Firmicutes and that aci1 occurs in bacteria scattered across the Negativicute clade, suggesting lateral gene transfer. In the reference A. intestini RyC-MR95 genome, we found transposons residing within a tailed prophage context are likely vehicles for aci1's mobility. We found aci1 in 56 (4.4%) of 1,267 human gut metagenomes, mostly hosted within A. intestini, and, where could be determined, mostly within a consistent mobile element constellation. These samples are from Europe, China and the USA, showing that aci1 is distributed globally. We found that for most Negativicute assemblies with aci1, the prophage observed in A. instestini is absent, but in all cases aci1 is flanked by varying transposons. The chimeric mobile elements we identify here likely have a complex evolutionary history and potentially provide multiple complementary mechanisms for antibiotic resistance gene transfer both within and between cells.}, } @article {pmid30010322, year = {2018}, author = {Stauber, RH and Siemer, S and Becker, S and Ding, GB and Strieth, S and Knauer, SK}, title = {Small Meets Smaller: Effects of Nanomaterials on Microbial Biology, Pathology, and Ecology.}, journal = {ACS nano}, volume = {12}, number = {7}, pages = {6351-6359}, doi = {10.1021/acsnano.8b03241}, pmid = {30010322}, issn = {1936-086X}, abstract = {As functionalities and levels of complexity in nanomaterials have increased, unprecedented control over microbes has been enabled, as well. In addition to being pathogens and relevant to the human microbiome, microbes are key players for sustainable biotechnology. To overcome current constraints, mechanistic understanding of nanomaterials' physicochemical characteristics and parameters at the nano-bio interface affecting nanomaterial-microbe crosstalk is required. In this Perspective, we describe key nanomaterial parameters and biological outputs that enable controllable microbe-nanomaterial interactions while minimizing design complexity. We discuss the role of biomolecule coronas, including the problem of nanoantibiotic resistance, and speculate on the effects of nanomaterial-microbe complex formation on the outcomes and fates of microbial pathogens. We close by summarizing our current knowledge and noting areas that require further exploration to overcome current limitations for next-generation practical applications of nanotechnology in medicine and agriculture.}, } @article {pmid30009382, year = {2018}, author = {Ceccarelli, F and Orrù, G and Pilloni, A and Bartosiewicz, I and Perricone, C and Martino, E and Lucchetti, R and Fais, S and Vomero, M and Olivieri, M and di Franco, M and Priori, R and Riccieri, V and Scrivo, R and Shoenfeld, Y and Alessandri, C and Conti, F and Polimeni, A and Valesini, G}, title = {Porphyromonas gingivalis in the tongue biofilm is associated with clinical outcome in rheumatoid arthritis patients.}, journal = {Clinical and experimental immunology}, volume = {}, number = {}, pages = {}, doi = {10.1111/cei.13184}, pmid = {30009382}, issn = {1365-2249}, abstract = {Several studies have suggested a link between human microbiome and rheumatoid arthritis (RA) development. Porphyromonas gingivalis seems involved in RA initiation and progression, as supported by the high occurrence of periodontitis. In this case-control study, we analysed tongue P. gingivalis presence and quantification in a large healthy and RA cohort. We enrolled 143 RA patients [male/female (M/F) 32/111, mean ± standard deviation (s.d.), age 57·5 ± 19·8 years, mean ± s.d. disease duration 155·9 ± 114·7 months); 36 periodontitis patients (M/F 11/25, mean ± s.d., age 56 ± 9·9 years, mean ± s.d. disease duration 25·5 ± 20·9 months); and 57 patients (M/F 12/45, mean ± s.d., age 61·4 ± 10·9 years, mean ± s.d. disease duration 62·3 ± 66·9 months) with knee osteoarthritis or fibromyalgia. All subjects underwent a standard cytological swab to identify the rate of P. gingivalis/total bacteria by using quantitative real-time polymerase chain reaction. The prevalence of P. gingivalis resulted similarly in RA and periodontitis patients (48·9 versus 52·7%, P = not significant). Moreover, the prevalence of this pathogen was significantly higher in RA and periodontitis patients in comparison with control subjects (P = 0·01 and P = 0·003, respectively). We found a significant correlation between P. gingivalis rate in total bacteria genomes and disease activity score in 28 joints (DAS28) (erythrocyte sedimentation rate) (r = 0·4, P = 0·01). RA patients in remission showed a significantly lower prevalence of P. gingivalis in comparison with non-remission (P = 0·02). We demonstrated a significant association between the percentage of P. gingivalis on the total tongue biofilm and RA disease activity (DAS28), suggesting that the oral cavity microbiological status could play a role in the pathogenic mechanisms of inflammation, leading to more active disease.}, } @article {pmid30007202, year = {2018}, author = {Stegen, JC and Bottos, EM and Jansson, JK}, title = {A unified conceptual framework for prediction and control of microbiomes.}, journal = {Current opinion in microbiology}, volume = {44}, number = {}, pages = {20-27}, doi = {10.1016/j.mib.2018.06.002}, pmid = {30007202}, issn = {1879-0364}, abstract = {Microbiomes impact nearly all systems on Earth, and despite vast differences among systems, we contend that it is possible and highly beneficial to develop a unified conceptual framework for understanding microbiome dynamics that is applicable across systems. The ability to robustly predict and control environmental and human microbiomes would provide impactful opportunities to sustain and improve the health of ecosystems and humans alike. Doing so requires understanding the processes governing microbiome temporal dynamics, which currently presents an enormous challenge. We contend, however, that new opportunities can emerge by placing studies of both environmental and human microbiome temporal dynamics in the context of a unified conceptual framework. Our conceptual framework poses that factors influencing the temporal dynamics of microbiomes can be grouped into three broad categories: biotic and abiotic history, internal dynamics, and external forcing factors. Both environmental and human microbiome science study these factors, but not in a coordinated or consistent way. Here we discuss opportunities for greater crosstalk across these domains, such as leveraging specific ecological concepts from environmental microbiome science to guide optimization of strategies to manipulate human microbiomes towards improved health. To achieve unified understanding, it is necessary to have a common body of theory developed from explicit iteration between models and molecular-based characterization of microbiome dynamics across systems. Only through such model-experiment iteration will we eventually achieve prediction and control across microbiomes that impact ecosystem sustainability and human health.}, } @article {pmid30003599, year = {2018}, author = {Lorimer, J}, title = {Hookworms Make Us Human: The Microbiome, Eco-immunology, and a Probiotic Turn in Western Health Care.}, journal = {Medical anthropology quarterly}, volume = {}, number = {}, pages = {}, doi = {10.1111/maq.12466}, pmid = {30003599}, issn = {0745-5194}, abstract = {Historians of science have identified an ecological turn underway in immunology, driven by the mapping of the human microbiome and wider environmentalist anxieties. A figure is emerging of the human as a holobiont, composed of microbes and threatened by both microbial excess and microbial absence. Antimicrobial approaches to germ warfare are being supplemented by probiotic approaches to restoring microbial life. This article examines the political ecology of this probiotic turn in Western health care. It focuses on Necator americanus-a species of human hookworm-and its relations with immunologists. The analysis moves from a history of human disentanglement from hookworm, to contemporary anxieties about their absence. It examines the reintroduction of worms for helminthic therapy and explores emerging trajectories for probiotic health care involving the synthesis, modification, and/or restoration of worms and their salutary ecologies. The conclusion differentiates these trajectories and identifies an emerging model of "post-paleo" microbiopolitics. This article is protected by copyright. All rights reserved.}, } @article {pmid30001289, year = {2018}, author = {Archibugi, L and Signoretti, M and Capurso, G}, title = {The Microbiome and Pancreatic Cancer: An Evidence-based Association?.}, journal = {Journal of clinical gastroenterology}, volume = {52 Suppl 1, Proceedings from the 9th Probiotics, Prebiotics and New Foods, Nutraceuticals and Botanicals for Nutrition & Human and Microbiota Health Meeting, held in Rome, Italy from September 10 to 12, 2017}, number = {}, pages = {S82-S85}, doi = {10.1097/MCG.0000000000001092}, pmid = {30001289}, issn = {1539-2031}, abstract = {Many risk factors for pancreatic cancer are related with microbiome alteration. In the past few years, the human microbiome and its relation with the immune system have been linked with carcinogenesis of different organs distant from the gut, including the pancreas. Patterns of oral microbiome associated with periodontitis are associated with an increased risk of pancreatic cancer, possibly because of the increased systemic inflammatory response, or to the capacity of some specific bacteria to alter the host immune response, making it more favorable to cancer cells. Helicobacter pylori infection when affecting the gastric body mucosa with subsequent hypochlorhydria also seems associated with an increased risk of pancreatic cancer. The composition of the intestinal microbiome is different in animal models and in humans with pancreatic cancer who have a distinct microbiome population compared with controls. Some specific bacteria can migrate from the intestine to the pancreas, and their ablation restores the immune system activity through its reprogramming with a switch toward a Th1 response and displays a protective effect toward tumor growth. More research in this area might lead to progress in terms of pancreatic cancer prevention and treatment, possibly in association with immunotherapy.}, } @article {pmid29997602, year = {2018}, author = {Xiao, J and Chen, L and Johnson, S and Yu, Y and Zhang, X and Chen, J}, title = {Predictive Modeling of Microbiome Data Using a Phylogeny-Regularized Generalized Linear Mixed Model.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {1391}, doi = {10.3389/fmicb.2018.01391}, pmid = {29997602}, issn = {1664-302X}, abstract = {Recent human microbiome studies have revealed an essential role of the human microbiome in health and disease, opening up the possibility of building microbiome-based predictive models for individualized medicine. One unique characteristic of microbiome data is the existence of a phylogenetic tree that relates all the microbial species. It has frequently been observed that a cluster or clusters of bacteria at varying phylogenetic depths are associated with some clinical or biological outcome due to shared biological function (clustered signal). Moreover, in many cases, we observe a community-level change, where a large number of functionally interdependent species are associated with the outcome (dense signal). We thus develop "glmmTree," a prediction method based on a generalized linear mixed model framework, for capturing clustered and dense microbiome signals. glmmTree uses the similarity between microbiomes, which is defined based on the microbiome composition and the phylogenetic tree, to predict the outcome. The effects of other predictive variables (e.g., age, sex) can be incorporated readily in the regression framework. Additional tuning parameters enable a data-adaptive approach to capture signals at different phylogenetic depth and abundance level. Simulation studies and real data applications demonstrated that "glmmTree" outperformed existing methods in the dense and clustered signal scenarios.}, } @article {pmid29988721, year = {2018}, author = {Lourenςo, TGB and Spencer, SJ and Alm, EJ and Colombo, APV}, title = {Defining the gut microbiota in individuals with periodontal diseases: an exploratory study.}, journal = {Journal of oral microbiology}, volume = {10}, number = {1}, pages = {1487741}, doi = {10.1080/20002297.2018.1487741}, pmid = {29988721}, issn = {2000-2297}, abstract = {Background: This exploratory study aimed to characterize the gut microbiome of individuals with different periodontal conditions, and correlate it with periodontal inflammation and tissue destruction. Methods: Stool samples were obtained from individuals presenting periodontal health (PH = 7), gingivitis (G = 14) and chronic periodontitis (CP = 23). The intestinal microbiome composition was determined by Illumina MiSeq sequencing. Results: A lower alpha-diversity in the gut microbiome of individuals with CP was observed, although no significant difference among groups was found (p > 0.01). Firmicutes, Proteobacteria, Verrucomicrobia and Euryarchaeota were increased, whereas Bacteroidetes were decreased in abundance in patients with periodontitis compared to PH. Prevotella (genus), Comamonadaceae (family) and Lactobacillales (order) were detected in higher numbers in G, while Bacteroidales (order) was predominant in PH (p < 0.01). Significant correlations (rho = 0.337-0.468, p < 0.01) were found between OTUs representative of periodontal pathogens and attachment loss. Mogibacteriaceae, Ruminococcaceae and Prevotella were able to discriminate individuals with periodontal diseases from PH (overall accuracy = 84%). Oral taxa were detected in high numbers in all stool samples. Conclusions: Individuals with periodontal diseases present a less diverse gut microbiome consistent with other systemic inflammatory diseases. High numbers of oral taxa related to periodontal destruction and inflammation were detected in the gut microbiome of individuals regardless of periodontal status.}, } @article {pmid29984938, year = {2018}, author = {Li, BL and Cheng, L and Zhou, XD and Peng, X}, title = {[Research progress on the relationship between oral microbes and digestive system diseases].}, journal = {Hua xi kou qiang yi xue za zhi = Huaxi kouqiang yixue zazhi = West China journal of stomatology}, volume = {36}, number = {3}, pages = {331-335}, doi = {10.7518/hxkq.2018.03.019}, pmid = {29984938}, issn = {1000-1182}, abstract = {The human microbiome project promoted further understanding on human oral microbes. Besides oral diseases such as dental caries, periodontal disease, and oral cancer, oral microbes are closely associated with systematic diseases. They have a close connection with digestive system diseases and even contribute to the origination and progression of colorectal cancer. By reviewing recent studies involving oral microbe-related digestive systemic diseases, we aim to propose the considerable role of oral microbes in relation to digestive systemic diseases and the way of oral microbes to multiple organs of digestive system.}, } @article {pmid29983746, year = {2018}, author = {Tipton, L and Cuenco, KT and Huang, L and Greenblatt, RM and Kleerup, E and Sciurba, F and Duncan, SR and Donahoe, MP and Morris, A and Ghedin, E}, title = {Measuring associations between the microbiota and repeated measures of continuous clinical variables using a lasso-penalized generalized linear mixed model.}, journal = {BioData mining}, volume = {11}, number = {}, pages = {12}, doi = {10.1186/s13040-018-0173-9}, pmid = {29983746}, issn = {1756-0381}, support = {K24 HL123342/HL/NHLBI NIH HHS/United States ; U01 AI035042/AI/NIAID NIH HHS/United States ; U01 AI037984/AI/NIAID NIH HHS/United States ; U01 HL098962/HL/NHLBI NIH HHS/United States ; UL1 RR024153/RR/NCRR NIH HHS/United States ; U01 AI031834/AI/NIAID NIH HHS/United States ; U01 AI035004/AI/NIAID NIH HHS/United States ; U01 AI034989/AI/NIAID NIH HHS/United States ; UL1 TR000124/TR/NCATS NIH HHS/United States ; U01 AI037613/AI/NIAID NIH HHS/United States ; M01 RR000722/RR/NCRR NIH HHS/United States ; U01 AI035041/AI/NIAID NIH HHS/United States ; UM1 AI035043/AI/NIAID NIH HHS/United States ; U01 AI034994/AI/NIAID NIH HHS/United States ; K24 HL087713/HL/NHLBI NIH HHS/United States ; UL1 TR000424/TR/NCATS NIH HHS/United States ; R01 HL090339/HL/NHLBI NIH HHS/United States ; U01 AI035043/AI/NIAID NIH HHS/United States ; U01 AI035040/AI/NIAID NIH HHS/United States ; U01 AI034993/AI/NIAID NIH HHS/United States ; UL1 TR000004/TR/NCATS NIH HHS/United States ; U01 AI103408/AI/NIAID NIH HHS/United States ; U01 AI035039/AI/NIAID NIH HHS/United States ; U01 HD032632/HD/NICHD NIH HHS/United States ; U01 AI042590/AI/NIAID NIH HHS/United States ; }, abstract = {Background: Human microbiome studies in clinical settings generally focus on distinguishing the microbiota in health from that in disease at a specific point in time. However, microbiome samples may be associated with disease severity or continuous clinical health indicators that are often assessed at multiple time points. While the temporal data from clinical and microbiome samples may be informative, analysis of this type of data can be problematic for standard statistical methods.

Results: To identify associations between microbiota and continuous clinical variables measured repeatedly in two studies of the respiratory tract, we adapted a statistical method, the lasso-penalized generalized linear mixed model (LassoGLMM). LassoGLMM can screen for associated clinical variables, incorporate repeated measures of individuals, and address the large number of species found in the microbiome. As is common in microbiome studies, when the number of variables is an order of magnitude larger than the number of samples LassoGLMM can be imperfect in its variable selection. We overcome this limitation by adding a pre-screening step to reduce the number of variables evaluated in the model. We assessed the use of this adapted two-stage LassoGLMM for its ability to determine which microbes are associated with continuous repeated clinical measures.We found associations (retaining a non-zero coefficient in the LassoGLMM) between 10 laboratory measurements and 43 bacterial genera in the oral microbiota, and between 2 cytokines and 3 bacterial genera in the lung. We compared our associations with those identified by the Wilcoxon test after dichotomizing our outcomes and identified a non-significant trend towards differential abundance between high and low outcomes. Our two-step LassoGLMM explained more of the variance seen in the outcome of interest than other variants of the LassoGLMM method.

Conclusions: We demonstrated a method that can account for the large number of genera detected in microbiome studies and repeated measures of clinical or longitudinal studies, allowing for the detection of strong associations between microbes and clinical measures. By incorporating the design strengths of repeated measurements and a prescreening step to aid variable selection, our two-step LassoGLMM will be a useful analytic method for investigating relationships between microbes and repeatedly measured continuous outcomes.}, } @article {pmid29976412, year = {2018}, author = {George Kerry, R and Patra, JK and Gouda, S and Park, Y and Shin, HS and Das, G}, title = {Benefaction of probiotics for human health: A review.}, journal = {Journal of food and drug analysis}, volume = {26}, number = {3}, pages = {927-939}, doi = {10.1016/j.jfda.2018.01.002}, pmid = {29976412}, issn = {1021-9498}, abstract = {Humans are a unique reservoir of heterogeneous and vivacious group of microbes, which together forms the human-microbiome superorganism. Human gut serves as a home to over 100-1000 microbial species, which primarily modulate the host internal environment and thereby, play a major role in host health. This spectacular symbiotic relationship has attracted extensive research in this field. More specifically, these organisms play key roles in defense function, eupepsia along with catabolism and anabolism, and impact brain-gut responses. The emergence of microbiota with resistance and tolerance to existing conventional drugs and antibiotics has decreased the drug efficacies. Furthermore, the modern biotechnology mediated nano-encapsulated multiplex supplements appear to be high cost and inconvenient. Henceforth, a simple, low-cost, receptive and intrinsic approach to achieve health benefits is vital in the present era. Supplementation with probiotics, prebiotics, and synbiotics has shown promising results against various enteric pathogens due to their unique ability to compete with pathogenic microbiota for adhesion sites, to alienate pathogens or to stimulate, modulate and regulate the host's immune response by initiating the activation of specific genes in and outside the host intestinal tract. Probiotics have also been shown to regulate fat storage and stimulate intestinal angiogenesis. Hence, this study aims to underline the possible beneficial impact of probiotics for human health and medical sectors and for better lifestyle.}, } @article {pmid29974051, year = {2018}, author = {Fankhauser, M and Moser, C and Nyfeler, T}, title = {Patents as Early Indicators of Technology and Investment Trends: Analyzing the Microbiome Space as a Case Study.}, journal = {Frontiers in bioengineering and biotechnology}, volume = {6}, number = {}, pages = {84}, doi = {10.3389/fbioe.2018.00084}, pmid = {29974051}, issn = {2296-4185}, abstract = {The human microbiome is the collective of microbes living in symbiosis on and within humans. Modulating its composition and function has become an attractive means for the prevention and treatment of a variety of diseases including cancer. Since the initiation of the human microbiome project in 2007, the number of academic publications and active patent families around the microbiome has grown exponentially. Screening patent databases can be useful for the early detection and the tracking of new technology trends. However, it is not sufficient to assess portfolio sizes because emerging players with small but high-quality patent portfolios will be missed within the noise of large but low-quality portfolio owners. Here we used the consolidated database and software tool PatentSight to benchmark patent portfolios, and to analyze key patent owners and innovators in the microbiome space. Our study shows how in-depth patent analyses combining qualitative and quantitative parameters can identify actionable early indicators of technology and investment trends from large patent datasets.}, } @article {pmid29973493, year = {2018}, author = {Castilla, IA and Woods, DF and Reen, FJ and O'Gara, F}, title = {Harnessing Marine Biocatalytic Reservoirs for Green Chemistry Applications through Metagenomic Technologies.}, journal = {Marine drugs}, volume = {16}, number = {7}, pages = {}, doi = {10.3390/md16070227}, pmid = {29973493}, issn = {1660-3397}, mesh = {Animals ; Aquatic Organisms/*metabolism ; Biocatalysis ; Esterases/metabolism ; Humans ; Lipase/metabolism ; Metagenomics/methods ; }, abstract = {In a demanding commercial world, large-scale chemical processes have been widely utilised to satisfy consumer related needs. Chemical industries are key to promoting economic growth and meeting the requirements of a sustainable industrialised society. The market need for diverse commodities produced by the chemical industry is rapidly expanding globally. Accompanying this demand is an increased threat to the environment and to human health, due to waste produced by increased industrial production. This increased demand has underscored the necessity to increase reaction efficiencies, in order to reduce costs and increase profits. The discovery of novel biocatalysts is a key method aimed at combating these difficulties. Metagenomic technology, as a tool for uncovering novel biocatalysts, has great potential and applicability and has already delivered many successful achievements. In this review we discuss, recent developments and achievements in the field of biocatalysis. We highlight how green chemistry principles through the application of biocatalysis, can be successfully promoted and implemented in various industrial sectors. In addition, we demonstrate how two novel lipases/esterases were mined from the marine environment by metagenomic analysis. Collectively these improvements can result in increased efficiency, decreased energy consumption, reduced waste and cost savings for the chemical industry.}, } @article {pmid29963639, year = {2018}, author = {Nieves-Ramírez, ME and Partida-Rodríguez, O and Laforest-Lapointe, I and Reynolds, LA and Brown, EM and Valdez-Salazar, A and Morán-Silva, P and Rojas-Velázquez, L and Morien, E and Parfrey, LW and Jin, M and Walter, J and Torres, J and Arrieta, MC and Ximénez-García, C and Finlay, BB}, title = {Asymptomatic Intestinal Colonization with Protist Blastocystis Is Strongly Associated with Distinct Microbiome Ecological Patterns.}, journal = {mSystems}, volume = {3}, number = {3}, pages = {}, doi = {10.1128/mSystems.00007-18}, pmid = {29963639}, issn = {2379-5077}, abstract = {Blastocystis is the most prevalent protist of the human intestine, colonizing approximately 20% of the North American population and up to 100% in some nonindustrialized settings. Blastocystis is associated with gastrointestinal and systemic disease but can also be an asymptomatic colonizer in large populations. While recent findings in humans have shown bacterial microbiota changes associated with this protist, it is unknown whether these occur due to the presence of Blastocystis or as a result of inflammation. To explore this, we evaluated the fecal bacterial and eukaryotic microbiota in 156 asymptomatic adult subjects from a rural population in Xoxocotla, Mexico. Colonization with Blastocystis was strongly associated with an increase in bacterial alpha diversity and broad changes in beta diversity and with more discrete changes to the microbial eukaryome. More than 230 operational taxonomic units (OTUs), including those of dominant species Prevotella copri and Ruminococcus bromii, were differentially abundant in Blastocystis-colonized individuals. Large functional changes accompanied these observations, with differential abundances of 202 (out of 266) predicted metabolic pathways (PICRUSt), as well as lower fecal concentrations of acetate, butyrate, and propionate in colonized individuals. Fecal calprotectin was markedly decreased in association with Blastocystis colonization, suggesting that this ecological shift induces subclinical immune consequences to the asymptomatic host. This work is the first to show a direct association between the presence of Blastocystis and shifts in the gut bacterial and eukaryotic microbiome in the absence of gastrointestinal disease or inflammation. These results prompt further investigation of the role Blastocystis and other eukaryotes play within the human microbiome. IMPORTANCE Given the results of our study and other reports of the effects of the most common human gut protist on the diversity and composition of the bacterial microbiome, Blastocystis and, possibly, other gut protists should be studied as ecosystem engineers that drive community diversity and composition.}, } @article {pmid29963028, year = {2018}, author = {Petrova, MI and Macklaim, JM and Wuyts, S and Verhoeven, T and Vanderleyden, J and Gloor, GB and Lebeer, S and Reid, G}, title = {Comparative Genomic and Phenotypic Analysis of the Vaginal Probiotic Lactobacillus rhamnosus GR-1.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {1278}, doi = {10.3389/fmicb.2018.01278}, pmid = {29963028}, issn = {1664-302X}, abstract = {Lactobacillus represents a versatile bacterial genus, which can adapt to a wide variety of ecological niches, including human body sites such as the intestinal and urogenital tract. In this study, the complete genome sequence of the vaginal probiotic Lactobacillus rhamnosus GR-1 was determined and compared to other L. rhamnosus strains at genomic and phenotypic level. The strain GR-1 was originally isolated from a female urethra, and was assessed with L. rhamnosus GG from a feces sample of a healthy male, and L. rhamnosus LC705 from a dairy product. A key difference is the absence in GR-1 and LC705 of the spaCBA locus required for pili-mediated intestinal epithelial adhesion. In addition, the L. rhamnosus GR-1 genome contains a unique cluster for exopolysaccharide production, which is postulated to synthesize glucose-rich, rhamnose-lacking exopolysaccharide molecules that are different from the galactose-rich extracellular polysaccharide of L. rhamnosus GG. Compared to L. rhamnosus GG, L. rhamnosus GR-1 was also genetically predicted and experimentally shown to better metabolize lactose and maltose, and to better withstand oxidative stress, which is of relevance in the vagina. This study could thus provide a molecular framework for the selection of the optimal probiotic strain for each targeted niche and condition, but further substantiation of niche adaptation mechanisms of lactobacilli is warranted.}, } @article {pmid29962006, year = {2018}, author = {Jakobsen, TH and Eickhardt, SR and Gheorghe, AG and Stenqvist, C and Sønderholm, M and Stavnsberg, C and Jensen, PØ and Odgaard, A and Whiteley, M and Moser, C and Hvolris, J and Hougen, HP and Bjarnsholt, T}, title = {Implants induce a new niche for microbiomes.}, journal = {APMIS : acta pathologica, microbiologica, et immunologica Scandinavica}, volume = {126}, number = {8}, pages = {685-692}, doi = {10.1111/apm.12862}, pmid = {29962006}, issn = {1600-0463}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Bacteria/classification/*isolation & purification ; Bacterial Typing Techniques ; Bone Regeneration/physiology ; Case-Control Studies ; Female ; Foreign Bodies/*microbiology ; Fractures, Bone/microbiology/surgery ; Fungi/classification/*isolation & purification ; Humans ; Male ; Middle Aged ; Mycological Typing Techniques ; Prostheses and Implants/*microbiology ; Prosthesis Failure ; Prosthesis-Related Infections/*microbiology ; }, abstract = {Although much work is being done to develop new treatments, research and knowledge regarding factors underlying implant-related microbial colonization leading to infection are less comprehensive. Presence of microorganisms in and around implants clinically characterized as uninfected remains unknown. The objective of this study was to detect and identify bacteria and fungi on implants from various groups of patients with no prior indications of implant related infections. Patient samples (implants and tissue) were collected from five different hospitals in the Capital region of Denmark. By in-depth microbiological detection methods, we examined the prevalence of bacteria and fungi on 106 clinically uninfected implants from four patient groups (aseptic loosening, healed fractures, craniofacial complications and recently deceased). Of 106 clinically uninfected implants and 39 negative controls investigated, 66% were colonized by bacteria and 40% were colonized by fungi (p < 0.0001 compared to negative controls). A large number of microbes were found to colonize the implants, however, the most prevalent microbes present were not common aetiological agents of implant infections. The findings indicate that implants provide a distinct niche for microbial colonization. These data have broad implications for medical implant recipients, as well as for supporting the idea that the presence of foreign objects in the body alters the human microbiome by providing new colonization niches.}, } @article {pmid29960810, year = {2018}, author = {Primec, M and Klemenak, M and Di Gioia, D and Aloisio, I and Bozzi Cionci, N and Quagliariello, A and Gorenjak, M and Mičetić-Turk, D and Langerholc, T}, title = {Clinical intervention using Bifidobacterium strains in celiac disease children reveals novel microbial modulators of TNF-α and short-chain fatty acids.}, journal = {Clinical nutrition (Edinburgh, Scotland)}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.clnu.2018.06.931}, pmid = {29960810}, issn = {1532-1983}, abstract = {BACKGROUND & AIMS: Celiac disease (CD) is an immune-mediated systemic disease, caused by ingestion of gluten in genetically predisposed individuals. Gut microbiota dysbiosis might play a significant role in pathogenesis of chronic enteropathies and its modulation can be used as an intervention strategy in CD as well. In this study, we aimed to identify correlations between fecal microbiota, serum tumor necrosis factor alpha (TNF-α) and fecal short-chain fatty acids (SCFAs) in healthy children and children with CD after administration of probiotic Bifidobacterium breve BR03 and B632.

METHODS: A double-blind placebo-controlled study enrolled 40 children with CD (CD) and 16 healthy children (HC). CD children were randomly allocated into two groups, of which 20 belonged to the placebo (PL) group and 20 to the Probiotic (PR) group. The PR group received a probiotic formulation containing a mixture of 2 strains, B. breve BR03 (DSM 16604) and B. breve B632 (DSM 24706) in 1:1 ratio for 3 months. Subsequently, for statistical analysis, blood and fecal samples from CD children (on enrolment - T0 and after 3 months, at the end of intervention with probiotic/placebo - T1) and HC children were used. The HC group was sampled only once (T0).

RESULTS: Verrucomicrobia, Parcubacteria and some yet unknown phyla of Bacteria and Archaea may be involved in the disease, indicated by a strong correlation to TNF-α. Likewise, Proteobacteria strongly correlated with fecal SCFAs concentration. The effect of probiotic administration has disclosed a negative correlation between Verrucomicrobia, some unknown phyla of Bacteria, Synergistetes, Euryarchaeota and some SCFAs, turning them into an important target in microbiome restoration process. Synergistetes and Euryarchaeota may have a role in the anti-inflammatory process in healthy human gut.

CONCLUSIONS: Our results highlight new phyla, which may have an important relation to disease-related parameters, CD itself and health.}, } @article {pmid29951378, year = {2018}, author = {Scapaticci, M and Bartolini, A and Del Chierico, F and Accardi, C and Di Girolamo, F and Masotti, A and Muraca, M and Putignani, L}, title = {Phenotypic typing and epidemiological survey of antifungal resistance of Candida species detected in clinical samples of Italian patients in a 17 months' period.}, journal = {Germs}, volume = {8}, number = {2}, pages = {58-66}, doi = {10.18683/germs.2018.1132}, pmid = {29951378}, issn = {2248-2997}, abstract = {Introduction: Yeast pathogens are emerging agents of nosocomial as well as community-acquired infections and their rapid and accurate identification is crucial for a better management of high-risk patients and for an adequate treatment.

Methods: We performed a retrospective review of 156 yeast isolates collected during a 17 months' period of regular clinical practice at the Microbiology Department of San Camillo Hospital in Treviso, Italy and analyzed by the traditional culture-based method combined with matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS).

Results: Out of all the samples collected MALDI-TOF MS was able to characterize with a MT score ≥1.7 (accurate result at species level) 12 different yeast and yeast-like species from 140 samples: Candida albicans (63.7%), Candida glabrata (13.6%), Saccharomyces cerevisiae (6.5%), Candida parapsilosis (5.7%), Candida tropicalis (2.1%), Candida pararugosa (2.1%), Candida guilliermondii (2.1%), Candida kefyr (1.4%), Candida lusitaniae (0.7%), Candida palmioleophila (0.7%), Geotrichum silvicola (0.7%), Rhodotorula mucilaginosa (0.7%). Susceptibility testing toward seven common antifungal agents showed a characteristic MIC distribution of C. albicans isolates for echinocandins: particularly we noticed that 72% and 46% of C. albicans showed an MIC value close to clinical breakpoint as defined by EUCAST, respectively for anidulafungin and micafungin.

Conclusion: Accurate identification of microorganisms and the study of their antifungal susceptibility allow to understand the epidemiology of a particular area, permitting the choice of the most appropriate early antifungal treatment.}, } @article {pmid29951086, year = {2018}, author = {Hadrich, D}, title = {Microbiome Research Is Becoming the Key to Better Understanding Health and Nutrition.}, journal = {Frontiers in genetics}, volume = {9}, number = {}, pages = {212}, doi = {10.3389/fgene.2018.00212}, pmid = {29951086}, issn = {1664-8021}, abstract = {The human microbiome has emerged as the crucial moderator in the interactions between food and our body. It is increasingly recognised that the microbiome can change our mind and health status, or switch on a wide range of diseases including cancer, cardio-metabolic diseases, allergies, and obesity. The causes of diseases are often only partially understood. However, nutrients, metabolites, and microbes are increasingly regarded as key players, even where the complete disease mechanisms remain unclear. The key to progress in the future will be to use and exploit additional, newly emerging disciplines such as metagenomics to complement patient information and to bring our understanding of diseases and the interrelation and effects of nutritional molecules to the next level. The EU has already funded 216 projects under the 7th Framework Programme and Horizon 2020 programmes to promote metagenomics and to advance our knowledge of microbes. This support started with the catalysing MetaHIT project that has produced a catalogue of gut microbes, and has arrived now at the very multi-disciplinary SYSCID action looking at how the microbiome is driving its resilience potential and our health. Together, these projects involve an investment of more than €498 M. However, in Horizon 2020, the new EU Health and Food Work Programmes for 2018-2020 go even further by setting new goals to find applications and to generate more knowledge on the microbiome, nutrition, various hosts of microbes, and their relation to health and disease. The big vision is to modulate health and diseases via the microbiome and nutrition, while at the same time other factors such as omics, molecular signatures, and lifestyle are constant. In this way, microbiome and nutrition research is moving from an isolated and despised offside position to a beacon of hope with a lot of potential and possibilities.}, } @article {pmid29943448, year = {2018}, author = {Marchesi, JR}, title = {Advancing microbiome research.}, journal = {Immunology}, volume = {}, number = {}, pages = {}, doi = {10.1111/imm.12973}, pmid = {29943448}, issn = {1365-2567}, } @article {pmid29942682, year = {2018}, author = {Paul, C and Bayrychenko, Z and Junier, T and Filippidou, S and Beck, K and Bueche, M and Greub, G and Bürgmann, H and Junier, P}, title = {Dissemination of antibiotic resistance genes associated with the sporobiota in sediments impacted by wastewater.}, journal = {PeerJ}, volume = {6}, number = {}, pages = {e4989}, doi = {10.7717/peerj.4989}, pmid = {29942682}, issn = {2167-8359}, abstract = {Aquatic ecosystems serve as a dissemination pathway and a reservoir of both antibiotic resistant bacteria (ARB) and antibiotic resistance genes (ARG). In this study, we investigate the role of the bacterial sporobiota to act as a vector for ARG dispersal in aquatic ecosystems. The sporobiota was operationally defined as the resilient fraction of the bacterial community withstanding a harsh extraction treatment eliminating the easily lysed fraction of the total bacterial community. The sporobiota has been identified as a critical component of the human microbiome, and therefore potentially a key element in the dissemination of ARG in human-impacted environments. A region of Lake Geneva in which the accumulation of ARG in the sediments has been previously linked to the deposition of treated wastewater was selected to investigate the dissemination of tet(W) and sul1, two genes conferring resistance to tetracycline and sulfonamide, respectively. Analysis of the abundance of these ARG within the sporobiome (collection of genes of the sporobiota) and correlation with community composition and environmental parameters demonstrated that ARG can spread across the environment with the sporobiota being the dispersal vector. A highly abundant OTU affiliated with the genus Clostridium was identified as a potential specific vector for the dissemination of tet(W), due to a strong correlation with tet(W) frequency (ARG copy numbers/ng DNA). The high dispersal rate, long-term survival, and potential reactivation of the sporobiota constitute a serious concern in terms of dissemination and persistence of ARG in the environment.}, } @article {pmid29941067, year = {2018}, author = {Marchesi, JR}, title = {Advancing microbiome research.}, journal = {Microbiology (Reading, England)}, volume = {164}, number = {8}, pages = {1005-1006}, doi = {10.1099/mic.0.000688}, pmid = {29941067}, issn = {1465-2080}, } @article {pmid29937405, year = {2018}, author = {Chang, CY and Yan, X and Crnovcic, I and Annaval, T and Chang, C and Nocek, B and Rudolf, JD and Yang, D and Hindra, and Babnigg, G and Joachimiak, A and Phillips, GN and Shen, B}, title = {Resistance to Enediyne Antitumor Antibiotics by Sequestration.}, journal = {Cell chemical biology}, volume = {25}, number = {9}, pages = {1075-1085.e4}, doi = {10.1016/j.chembiol.2018.05.012}, pmid = {29937405}, issn = {2451-9448}, support = {R01 CA078747/CA/NCI NIH HHS/United States ; R01 CA204484/CA/NCI NIH HHS/United States ; R01 GM115575/GM/NIGMS NIH HHS/United States ; }, abstract = {The enediynes, microbial natural products with extraordinary cytotoxicities, have been translated into clinical drugs. Two self-resistance mechanisms are known in the enediyne producers-apoproteins for the nine-membered enediynes and self-sacrifice proteins for the ten-membered enediyne calicheamicin. Here we show that: (1) tnmS1, tnmS2, and tnmS3 encode tiancimycin (TNM) resistance in its producer Streptomyces sp. CB03234, (2) tnmS1, tnmS2, and tnmS3 homologs are found in all anthraquinone-fused enediyne producers, (3) TnmS1, TnmS2, and TnmS3 share a similar β barrel-like structure, bind TNMs with nanomolar KD values, and confer resistance by sequestration, and (4) TnmS1, TnmS2, and TnmS3 homologs are widespread in nature, including in the human microbiome. These findings unveil an unprecedented resistance mechanism for the enediynes. Mechanisms of self-resistance in producers serve as models to predict and combat future drug resistance in clinical settings. Enediyne-based chemotherapies should now consider the fact that the human microbiome harbors genes encoding enediyne resistance.}, } @article {pmid29931340, year = {2018}, author = {van Dijkhuizen, EHP and Aidonopoulos, O and Ter Haar, NM and Pires Marafon, D and Magni-Manzoni, S and Ioannidis, YE and Putignani, L and Vastert, SJ and Malattia, C and De Benedetti, F and Martini, A}, title = {Prediction of inactive disease in juvenile idiopathic arthritis: a multicentre observational cohort study.}, journal = {Rheumatology (Oxford, England)}, volume = {57}, number = {10}, pages = {1752-1760}, doi = {10.1093/rheumatology/key148}, pmid = {29931340}, issn = {1462-0332}, abstract = {Objectives: To predict the occurrence of inactive disease in JIA in the first 2 years of disease.

Methods: An inception cohort of 152 treatment-naïve JIA patients with disease duration <6 months was analysed. Potential predictors were baseline clinical variables, joint US, gut microbiota composition and a panel of inflammation-related compounds in blood plasma. Various algorithms were employed to predict inactive disease according to Wallace criteria at 6-month intervals in the first 2 years. Performance of the models was evaluated using the split-cohort technique. The cohort was analysed in its entirety, and separate models were developed for oligoarticular patients, polyarticular RF negative patients and ANA positive patients.

Results: All models analysing the cohort as a whole showed poor performance in test data [area under the curve (AUC): <0.65]. The subgroup models performed better. Inactive disease was predicted by lower baseline juvenile arthritis DAS (JADAS)-71 and lower relative abundance of the operational taxonomic unit Mogibacteriaceae for oligoarticular patients (AUC in test data: 0.69); shorter duration of morning stiffness, higher haemoglobin and lower CXCL-9 levels at baseline for polyarticular RF negative patients (AUC in test data: 0.69); and shorter duration of morning stiffness and higher baseline haemoglobin for ANA positive patients (AUC in test data: 0.72).

Conclusion: Inactive disease could not be predicted with satisfactory accuracy in the whole cohort, likely due to disease heterogeneity. Interesting predictors were found in more homogeneous subgroups. These need to be validated in future studies.}, } @article {pmid29927545, year = {2018}, author = {Bäumel, S and Tytgat, HLP and Nemec, B and Schmidt, R and Chia, LW and Smidt, H}, title = {Fifty Percent Human - how art brings us in touch with our microbial cohabitants.}, journal = {Microbial biotechnology}, volume = {11}, number = {4}, pages = {571-574}, doi = {10.1111/1751-7915.13285}, pmid = {29927545}, issn = {1751-7915}, abstract = {The Human Microbiome, as well as the exploration of the microorganisms inhabiting the human body, are not only integral to the field of microbiology but represent an intrinsic part of all human beings. Consequently, along with scientists, artists have been inspired by the microbiome: transforming it in to tangible artefacts in order to critically question, reflect on and break down the barrier between humans and their microcohabitants. By artistic means, artists help us to understand how microbial research topics are inevitably affected by societal influences, including (health) politics, economics and the arts. Fifty Percent Human is a multidisciplinary artistic research project that aims to reshape our understanding of the human body and its environment as well as to explore possibilities for conscious coexistence in order to bridge the gap between science and society.}, } @article {pmid29922272, year = {2018}, author = {Del Chierico, F and Abbatini, F and Russo, A and Quagliariello, A and Reddel, S and Capoccia, D and Caccamo, R and Ginanni Corradini, S and Nobili, V and De Peppo, F and Dallapiccola, B and Leonetti, F and Silecchia, G and Putignani, L}, title = {Gut Microbiota Markers in Obese Adolescent and Adult Patients: Age-Dependent Differential Patterns.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {1210}, doi = {10.3389/fmicb.2018.01210}, pmid = {29922272}, issn = {1664-302X}, abstract = {Obesity levels, especially in children, have dramatically increased over the last few decades. Recently, several studies highlighted the involvement of gut microbiota in the pathophysiology of obesity. We investigated the composition of gut microbiota in obese adolescents and adults compared to age-matched normal weight (NW) volunteers in order to assemble age- and obesity-related microbiota profiles. The composition of gut microbiota was analyzed by 16S rRNA-based metagenomics. Ecological representations of microbial communities were computed, and univariate, multivariate, and correlation analyses performed on bacterial profiles. The prediction of metagenome functional content from 16S rRNA gene surveys was carried out. Ecological analyses revealed a dissimilarity among the subgroups, and resultant microbiota profiles differed between obese adolescents and adults. Using statistical analyses, we assigned, as microbial markers, Faecalibacterium prausnitzii and Actinomyces to the microbiota of obese adolescents, and Parabacteroides, Rikenellaceae, Bacteroides caccae, Barnesiellaceae, and Oscillospira to the microbiota of NW adolescents. The predicted metabolic profiles resulted different in adolescent groups. Particularly, biosynthesis of primary bile acid and steroid acids, metabolism of fructose, mannose, galactose, butanoate, and pentose phosphate and glycolysis/gluconeogenesis were for the majority associated to obese, while biosynthesis and metabolism of glycan, biosynthesis of secondary bile acid, metabolism of steroid hormone and lipoic acid were associated to NW adolescents. Our study revealed unique features of gut microbiota in terms of ecological patterns, microbial composition and metabolism in obese patients. The assignment of novel obesity bacterial markers may open avenues for the development of patient-tailored treatments dependent on age-related microbiota profiles.}, } @article {pmid29917039, year = {2018}, author = {Noguera-Julian, M and González-Beiras, C and Parera, M and Kapa, A and Paredes, R and Mitjà, O}, title = {Aetiological Characterization of the Cutaneous Ulcer Syndrome in Papua New Guinea using Shotgun Metagenomics.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {}, number = {}, pages = {}, doi = {10.1093/cid/ciy502}, pmid = {29917039}, issn = {1537-6591}, abstract = {Background: Treponema pallidum subsp. pertenue and Haemophilus ducreyi are causative agents of cutaneous ulcer (CU) in yaws endemic regions in the tropics. However, a significant proportion of CU patients remain PCR-negative for both bacterial agents. We aimed to identify potential additional aetiological agents of CU in a yaws-endemic region.

Methods: This population-based cohort study included children in Lihir Island (Papua New Guinea) examined during a yaws eradication campaign in Oct 2013-Oct 2014. All consenting patients with atraumatic exudative ulcers of more than 1 cm diameter were enrolled. Lesional swabs were collected for Real-Time PCR testing for T. p .pertenue and H. ducreyi. We then performed shotgun whole DNA metagenomics sequencing on extracted DNA and taxonomically assigned shotgun sequences using a human microbiome reference.

Findings: Sequence data was available for 122 samples. Shotgun sequencing showed high classification agreement relative to PCR testing: AUC for T. pallidum/H. ducreyi: 0.92/0.85 respectively. Clustering analysis of shotgun data revealed compositional clusters where the dominant species (median relative abundance ranged 32%-66%) was: H. ducreyi (23% of specimens), T. p. pertenue (16%), Streptococcus dysgalactiae (12%), Arcanobacterium haemolyticum (8%) and Corynebacterium diptheriae (8%). Sample clustering derived from ulcer microbial composition did not show geographical patterns.

Conclusion: These data suggest a diverse aetiology of skin ulcers in yaws-endemic areas, which may help design more accurate diagnostic tools and more effective antimicrobial treatment approaches to the cutaneous ulcer syndrome.}, } @article {pmid29915115, year = {2018}, author = {Shen, M and Yang, Y and Shen, W and Cen, L and McLean, JS and Shi, W and Le, S and He, X}, title = {A Linear Plasmid-Like Prophage of Actinomyces odontolyticus Promotes Biofilm Assembly.}, journal = {Applied and environmental microbiology}, volume = {84}, number = {17}, pages = {}, doi = {10.1128/AEM.01263-18}, pmid = {29915115}, issn = {1098-5336}, abstract = {The human oral cavity is home to a large number of bacteria and bacteriophages (phages). However, the biology of oral phages as members of the human microbiome is not well understood. Recently, we isolated Actinomyces odontolyticus subsp. actinosynbacter strain XH001 from the human oral cavity, and genomic analysis revealed the presence of an intact prophage named xhp1. Here, we demonstrated that xhp1 is a linear plasmid-like prophage, which is a newly identified phage of A. odontolyticus The prophage xhp1 genome is a 35-kb linear double-stranded DNA with 10-bp single-stranded, 3' cohesive ends. xhp1 exists extrachromosomally, with an estimated copy number of 5. Annotation of xhp1 revealed 54 open reading frames, while phylogenetic analysis suggests that it has limited similarity with other phages. xhp1 phage particles can be induced by mitomycin C and belong to the Siphoviridae family, according to transmission electron microscopic examination. The released xhp1 particles can reinfect the xhp1-cured XH001 strain and result in tiny blurry plaques. Moreover, xhp1 promotes XH001 biofilm formation through spontaneous induction and the release of host extracellular DNA (eDNA). In conclusion, we identified a linear plasmid-like prophage of A. odontolyticus, which enhances bacterial host biofilm assembly and could be beneficial to the host for its persistence in the oral cavity.IMPORTANCE The biology of phages as members of the human oral microbiome is understudied. Here, we report the characterization of xhp1, a novel linear plasmid-like prophage identified from a human oral isolate, Actinomyces odontolyticus subsp. actinosynbacter strain XH001. xhp1 can be induced and reinfect xhp1-cured XH001. The spontaneous induction of xhp1 leads to the lysis of a subpopulation of bacterial hosts and the release of eDNA that promotes biofilm assembly, thus potentially contributing to the persistence of A. odontolyticus within the oral cavity.}, } @article {pmid29913479, year = {2018}, author = {Ismail, T and Fatima, N and Muhammad, SA and Zaidi, SS and Rehman, N and Hussain, I and Tariq, NUS and Amirzada, I and Mannan, A}, title = {Prioritizing and modelling of putative drug target proteins of Candida albicans by systems biology approach.}, journal = {Acta biochimica Polonica}, volume = {65}, number = {2}, pages = {209-218}, doi = {10.18388/abp.2017_2327}, pmid = {29913479}, issn = {1734-154X}, abstract = {Candida albicans (Candida albicans) is one of the major sources of nosocomial infections in humans which may prove fatal in 30% of cases. The hospital acquired infection is very difficult to treat affectively due to the presence of drug resistant pathogenic strains, therefore there is a need to find alternative drug targets to cure this infection. In silico and computational level frame work was used to prioritize and establish antifungal drug targets of Candida albicans. The identification of putative drug targets was based on acquiring 5090 completely annotated genes of Candida albicans from available databases which were categorized into essential and non-essential genes. The result indicated that 9% of proteins were essential and could become potential candidates for intervention which might result in pathogen eradication. We studied cluster of orthologs and the subtractive genomic analysis of these essential proteins against human genome was made as a reference to minimize the side effects. It was seen that 14% of Candida albicans proteins were evolutionary related to the human proteins while 86% are non-human homologs. In the next step of compatible drug target selections, the non-human homologs were sequentially compared to the human microbiome data to minimize the potential effects against gut flora which accumulated to 38% of the essential genome. The sub-cellular localization of these candidate proteins in fungal cellular systems indicated that 80% of them are cytoplasmic, 10% are mitochondrial and the remaining 10% are associated with the cell wall. The role of these non-human and non-gut flora putative target proteins in Candida albicans biological pathways was studied. Due to their integrated and critical role in Candida albicans replication cycle, four proteins were selected for molecular modeling. For drug designing and development, four high quality and reliable protein models with more than 70% sequence identity were constructed. These proteins are used for the docking studies of the known and new ligands (unpublished data). Our study will be an effective framework for drug target identifications of pathogenic microbial strains and development of new therapies against the infections they cause.}, } @article {pmid29913309, year = {2018}, author = {Schirmer, M and Kumar, V and Netea, MG and Xavier, RJ}, title = {The causes and consequences of variation in human cytokine production in health.}, journal = {Current opinion in immunology}, volume = {54}, number = {}, pages = {50-58}, doi = {10.1016/j.coi.2018.05.012}, pmid = {29913309}, issn = {1879-0372}, abstract = {Cytokines are important cell-signaling molecules that activate and modulate immune responses. Major factors influencing cytokine variation in healthy individuals are host genetics, non-heritable factors and the microbiome. Genetic variation accounts for a significant part of heterogeneity in cytokine production by peripheral blood mononuclear cells. Variation in cytokines such as IL-6 and IL-6Ra is strongly influenced by heritability, suggesting an evolutionarily pressure for their genetic regulation that potentially contributes to differences in immune responsiveness between human populations. Non-heritable factors, including age, body weight and environmental variables such as seasonality, drive variation in baseline cytokine levels. Age further affects pathogen-induced lymphocyte-derived cytokine responses, whereas seasonality affects monocyte-derived cytokine production in response to influenza virus, Coxiella burnetti or Cryptococcus neoformans. Another influential factor that shapes the immune system is the human microbiome. Microbes and microbial products (e.g. short-chain fatty acids and tryptophan metabolites) possess strong immunomodulatory effects, induce regulatory T cells and lead to the diversification of B cells and the production of specific antibodies. In particular, differential TNFα and IFNγ production is associated with the gut microbiome. Understanding causes of variation in the healthy human immune system can reveal factors that lead to aberrant cytokine production in immune-related disorders.}, } @article {pmid29912913, year = {2018}, author = {McMillan, A and Rulisa, S and Gloor, GB and Macklaim, JM and Sumarah, M and Reid, G}, title = {Pilot assessment of probiotics for pregnant women in Rwanda.}, journal = {PloS one}, volume = {13}, number = {6}, pages = {e0195081}, doi = {10.1371/journal.pone.0195081}, pmid = {29912913}, issn = {1932-6203}, abstract = {BACKGROUND: While the global market for probiotics is soon to reach in excess of US$50 billion, the continent of Africa has been largely ignored, despite these products having the ability to reduce the burden of disease and death.

TRIAL DESIGN: The present randomised, blinded, placebo-controlled clinical trial was undertaken in Rwanda, a country devoid of well-documented probiotics. The primary outcome aim was to examine receptivity and compliance for orally administered probiotic capsules containing Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 in pregnant women and assess any initial side effects or changes to the vaginal microbiome.

METHODS: Pregnant women between the ages of 18 and 55 were recruited from the Nyamata District Hospital in Rwanda and randomly assigned to receive probiotic or placebo capsules for one month. Clinicians were blinded to the treatments.

RESULTS: The drop-out rate was 21%, with 13 of 18 women in the placebo group and 17 of 20 in the probiotic group completing the study. Only 13 women returned for birthing and additional sample collection. No side effects of either treatment group were reported. Microbiota and metabolomics data showed similar findings to those reported in the literature, with low bacterial diversity and Lactobacillus dominance associated with a healthy vagina, and birthing associated with high diversity. Despite the small sample size and lack of changes in the microbiota, women in the placebo arm were significantly more likely to give birth pre-term.

CONCLUSION: Overall women were receptive to the probiotic concept, but the lack of information on such products and logistical and economical challenges pose problems for wider population engagement.

TRIAL REGISTRATION: ClinicalTrials.gov NCT02150655.}, } @article {pmid29910789, year = {2018}, author = {Pannaraj, PS and Ly, M and Cerini, C and Saavedra, M and Aldrovandi, GM and Saboory, AA and Johnson, KM and Pride, DT}, title = {Shared and Distinct Features of Human Milk and Infant Stool Viromes.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {1162}, doi = {10.3389/fmicb.2018.01162}, pmid = {29910789}, issn = {1664-302X}, support = {K23 HD072774/HD/NICHD NIH HHS/United States ; }, abstract = {Infants acquire many of their microbes from their mothers during the birth process. The acquisition of these microbes is believed to be critical in the development of the infant immune system. Bacteria also are transmitted to the infant through breastfeeding, and help to form the microbiome of the infant gastrointestinal (GI) tract; it is unknown whether viruses in human milk serve to establish an infant GI virome. We examined the virome contents of milk and infant stool in a cohort of mother-infant pairs to discern whether milk viruses colonize the infant GI tract. We observed greater viral alpha diversity in milk than in infant stool, similar to the trend we found for bacterial communities from both sites. When comparing beta diversity, viral communities were mostly distinguishable between milk and infant stool, but each was quite distinct from adult stool, urine, and salivary viromes. There were significant differences in viral families in the infant stool (abundant bacteriophages from the family Siphoviridae) compared to milk (abundant bacteriophages from the family Myoviridae), which may reflect significant differences in the bacterial families identified from both sites. Despite the differences in viral taxonomy, we identified a significant number of shared viruses in the milk and stool from all mother-infant pairs. Because of the significant proportion of bacteriophages transmitted in these mother-infant pairs, we believe the transmission of milk phages to the infant GI tract may help to shape the infant GI microbiome.}, } @article {pmid29908759, year = {2018}, author = {Qiu, B and Al, K and Pena-Diaz, AM and Athwal, GS and Drosdowech, D and Faber, KJ and Burton, JP and O'Gorman, DB}, title = {Cutibacterium acnes and the shoulder microbiome.}, journal = {Journal of shoulder and elbow surgery}, volume = {27}, number = {10}, pages = {1734-1739}, doi = {10.1016/j.jse.2018.04.019}, pmid = {29908759}, issn = {1532-6500}, abstract = {BACKGROUND: Advances in DNA sequencing technologies have made it possible to detect microbial genome sequences (microbiomes) within tissues once thought to be sterile. We used this approach to gain insights into the likely sources of Cutibacterium acnes (formerly Propionibacterium acnes) infections within the shoulder.

METHODS: Tissue samples were collected from the skin, subcutaneous fat, anterior supraspinatus tendon, middle glenohumeral ligament, and humeral head cartilage of 23 patients (14 male and 9 female patients) during primary arthroplasty surgery. Total DNA was extracted and microbial 16S ribosomal RNA sequencing was performed using an Illumina MiSeq system. Data analysis software was used to generate operational taxonomic units for quantitative and statistical analyses.

RESULTS: After stringent removal of contamination, genomic DNA from various Acinetobacter species and from the Oxalobacteraceae family was identified in 74% of rotator cuff tendon tissue samples. C acnes DNA was detected in the skin of 1 male patient but not in any other shoulder tissues.

CONCLUSION: Our findings indicate the presence of a low-abundance microbiome in the rotator cuff and, potentially, in other shoulder tissues. The absence of C acnes DNA in all shoulder tissues assessed other than the skin is consistent with the hypothesis that C acnes infections are derived from skin contamination during surgery and not from opportunistic expansion of a resident C acnes population in the shoulder joint.}, } @article {pmid29908580, year = {2018}, author = {Ely, PH}, title = {Is psoriasis a bowel disease? Successful treatment with bile acids and bioflavonoids suggests it is.}, journal = {Clinics in dermatology}, volume = {36}, number = {3}, pages = {376-389}, doi = {10.1016/j.clindermatol.2018.03.011}, pmid = {29908580}, issn = {1879-1131}, abstract = {The gut is the largest lymphoid organ in the body. The human microbiome is composed of trillions of bacteria. The DNA of these bacteria dwarfs the human genome. Diet and ethanol can cause rapid shifts in the number and types of bacteria in the gut. The psoriatic microbiome is similar to that seen in alcoholics; there is a decrease in bacterial diversity and overgrowth of bacteria in the small bowel. Psoriatics often have liver disease and deficiencies in bile acids. Psoriasis is a disease characterized by a leaky gut. All of the comorbidities of this disease are due to systemic endotoxemia. Bacterial peptidoglycans absorbed from the gut have direct toxic effects on the liver and skin. Their absorption, as well as endotoxin absorption, must be eliminated to treat psoriasis successfully. Endotoxin absorption is markedly increased by ethanol and peppers. Bioflavonoids, such as quercetin and citrus bioflavonoids, prevent this absorption. Bile acids, given orally, break up endotoxin in the intestinal lumen. Pathogens, including Helicobacter pylori and Streptococcus pyogenes, must be eliminated with antimicrobial therapy for any treatment to work. A complete protocol for curing psoriasis is provided.}, } @article {pmid29902438, year = {2018}, author = {Milshteyn, A and Colosimo, DA and Brady, SF}, title = {Accessing Bioactive Natural Products from the Human Microbiome.}, journal = {Cell host & microbe}, volume = {23}, number = {6}, pages = {725-736}, doi = {10.1016/j.chom.2018.05.013}, pmid = {29902438}, issn = {1934-6069}, abstract = {Natural products have long played a pivotal role in the development of therapeutics for a variety of diseases. Traditionally, soil and marine environments have provided a rich reservoir from which diverse chemical scaffolds could be discovered. Recently, the human microbiome has been recognized as a promising niche from which secondary metabolites with therapeutic potential have begun to be isolated. In this Review, we address how the expansive history of identifying bacterial natural products in other environments is informing the approaches being brought to bear on the study of the human microbiota. We also touch on how these tools can lead to insights about microbe-microbe and host-microbe interactions and help generate biological hypotheses that may lead to developments of new therapeutic modalities.}, } @article {pmid29900563, year = {2018}, author = {Coleman, M and Elkins, C and Gutting, B and Mongodin, E and Solano-Aguilar, G and Walls, I}, title = {Microbiota and Dose Response: Evolving Paradigm of Health Triangle.}, journal = {Risk analysis : an official publication of the Society for Risk Analysis}, volume = {38}, number = {10}, pages = {2013-2028}, doi = {10.1111/risa.13121}, pmid = {29900563}, issn = {1539-6924}, abstract = {SRA Dose-Response and Microbial Risk Analysis Specialty Groups jointly sponsored symposia that addressed the intersections between the "microbiome revolution" and dose response. Invited speakers presented on innovations and advances in gut and nasal microbiota (normal microbial communities) in the first decade after the Human Microbiome Project began. The microbiota and their metabolites are now known to influence health and disease directly and indirectly, through modulation of innate and adaptive immune systems and barrier function. Disruption of healthy microbiota is often associated with changes in abundance and diversity of core microbial species (dysbiosis), caused by stressors including antibiotics, chemotherapy, and disease. Nucleic-acid-based metagenomic methods demonstrated that the dysbiotic host microbiota no longer provide normal colonization resistance to pathogens, a critical component of innate immunity of the superorganism. Diverse pathogens, probiotics, and prebiotics were considered in human and animal models (in vivo and in vitro). Discussion included approaches for design of future microbial dose-response studies to account for the presence of the indigenous microbiota that provide normal colonization resistance, and the absence of the protective microbiota in dysbiosis. As NextGen risk analysis methodology advances with the "microbiome revolution," a proposed new framework, the Health Triangle, may replace the old paradigm based on the Disease Triangle (focused on host, pathogen, and environment) and germophobia. Collaborative experimental designs are needed for testing hypotheses about causality in dose-response relationships for pathogens present in our environments that clearly compete in complex ecosystems with thousands of bacterial species dominating the healthy superorganism.}, } @article {pmid29899737, year = {2018}, author = {Xun, Z and Zhang, Q and Xu, T and Chen, N and Chen, F}, title = {Dysbiosis and Ecotypes of the Salivary Microbiome Associated With Inflammatory Bowel Diseases and the Assistance in Diagnosis of Diseases Using Oral Bacterial Profiles.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {1136}, doi = {10.3389/fmicb.2018.01136}, pmid = {29899737}, issn = {1664-302X}, abstract = {Inflammatory bowel diseases (IBDs) are chronic, idiopathic, relapsing disorders of unclear etiology affecting millions of people worldwide. Aberrant interactions between the human microbiota and immune system in genetically susceptible populations underlie IBD pathogenesis. Despite extensive studies examining the involvement of the gut microbiota in IBD using culture-independent techniques, information is lacking regarding other human microbiome components relevant to IBD. Since accumulated knowledge has underscored the role of the oral microbiota in various systemic diseases, we hypothesized that dissonant oral microbial structure, composition, and function, and different community ecotypes are associated with IBD; and we explored potentially available oral indicators for predicting diseases. We examined the 16S rRNA V3-V4 region of salivary bacterial DNA from 54 ulcerative colitis (UC), 13 Crohn's disease (CD), and 25 healthy individuals using Illumina sequencing. Distinctive sample clusters were driven by disease or health based on principal coordinate analysis (PCoA) of both the Operational Taxonomic Unit profile and Kyoto Encyclopedia of Genes and Genomes pathways. Comparisons of taxa abundances revealed enrichment of Streptococcaceae (Streptococcus) and Enterobacteriaceae in UC and Veillonellaceae (Veillonella) in CD, accompanied by depletion of Lachnospiraceae and [Prevotella] in UC and Neisseriaceae (Neisseria) and Haemophilus in CD, most of which have been demonstrated to exhibit the same variation tendencies in the gut of IBD patients. IBD-related oral microorganisms were associated with white blood cells, reduced basic metabolic processes, and increased biosynthesis and transport of substances facilitating oxidative stress and virulence. Furthermore, UC and CD communities showed robust sub-ecotypes that were not demographic or severity-specific, suggesting their value for future applications in precision medicine. Additionally, indicator species analysis revealed several genera indicative of UC and CD, which were confirmed in a longitudinal cohort. Collectively, this study demonstrates evident salivary dysbiosis and different ecotypes in IBD communities and provides an option for identifying at-risk populations, not only enhancing our understanding of the IBD microbiome apart from the gut but also offering a clinically useful strategy to track IBD as saliva can be sampled conveniently and non-invasively.}, } @article {pmid29898981, year = {2018}, author = {Bansal, S and Nguyen, JP and Leligdowicz, A and Zhang, Y and Kain, KC and Ricciuto, DR and Coburn, B}, title = {Rectal and Naris Swabs: Practical and Informative Samples for Analyzing the Microbiota of Critically Ill Patients.}, journal = {mSphere}, volume = {3}, number = {3}, pages = {}, doi = {10.1128/mSphere.00219-18}, pmid = {29898981}, issn = {2379-5042}, support = {FDN-14839//CIHR/Canada ; }, abstract = {Commensal microbiota are immunomodulatory, and their pathological perturbation can affect the risk and outcomes of infectious and inflammatory diseases. Consequently, the human microbiota is an emerging diagnostic and therapeutic target in critical illness. In this study, we compared four sample types-rectal, naris, and antecubital swabs and stool samples-for 16S rRNA gene microbiota sequencing in intensive care unit (ICU) patients. Stool samples were obtained in only 31% of daily attempts, while swabs were reliably obtained (≥97% of attempts). Swabs were compositionally distinct by anatomical site, and rectal swabs identified within-patient temporal trends in microbiota composition. Rectal swabs from ICU patients demonstrated differences from healthy stool similar to those observed in comparing stool samples from ICU patients to those from the same healthy controls. Rectal swabs are a useful complement to other sample types for analysis of the intestinal microbiota in critical illness, particularly when obtaining stool may not be feasible or practical.IMPORTANCE Perturbation of the microbiome has been correlated with various infectious and inflammatory diseases and is common in critically ill patients. Stool is typically used to sample the microbiota in human observational studies; however, it is often unavailable for collection from critically ill patients, reducing its utility as a sample type to study this population. Our research identified alternatives to stool for sampling the microbiota during critical illness. Rectal and naris swabs were practical alternatives for use in these patients, as they were observed to be more reliably obtained than stool, were suitable for culture-independent analysis, and successfully captured within- and between-patient microbiota differences.}, } @article {pmid29896176, year = {2018}, author = {Elbehery, AHA and Feichtmayer, J and Singh, D and Griebler, C and Deng, L}, title = {The Human Virome Protein Cluster Database (HVPC): A Human Viral Metagenomic Database for Diversity and Function Annotation.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {1110}, doi = {10.3389/fmicb.2018.01110}, pmid = {29896176}, issn = {1664-302X}, abstract = {Human virome, including those of bacteria (bacteriophages) have received an increasing attention recently, owing to the rapid developments in human microbiome research and the awareness of the far-reaching influence of microbiomes on health and disease. Nevertheless, human viromes are still underrepresented in literature making viruses a virtually untapped resource of diversity, functional and physiological information. Here we present the human virome protein cluster database as an effort to improve functional annotation and characterization of human viromes. The database was built out of hundreds of virome datasets from six different body sites. We also show the utility of this database through its use for the characterization of three bronchoalveolar lavage (BAL) viromes from one healthy control in addition to one moderate and one severe chronic obstructive pulmonary disease (COPD) patients. The use of the database allowed for a better functional annotation, which were otherwise poorly characterized when limited to annotation using sequences from full-length viral genomes. In addition, our BAL samples gave a first insight into viral communities of COPD patients and confirm a state of dysbiosis for viruses that increases with disease progression. Moreover, they shed light on the potential role of phages in the horizontal gene transfer of bacterial virulence factors, a phenomenon that highlights a possible contribution of phages to etiopathology.}, } @article {pmid29895255, year = {2018}, author = {Katsi, V and Didagelos, M and Skevofilax, S and Armenis, I and Kartalis, A and Vlachopoulos, C and Karvounis, H and Tousoulis, D}, title = {Gut Microbiome - Gut Dysbiosis - Arterial Hypertension: New Horizons.}, journal = {Current hypertension reviews}, volume = {}, number = {}, pages = {}, doi = {10.2174/1573402114666180613080439}, pmid = {29895255}, issn = {1875-6506}, abstract = {Arterial hypertension is a progressive cardiovascular syndrome arising from complex and interrelated etiologies. The human microbiome refers to the community of microorganisms that live in or on the human body. They influence human physiology by interfering in several processes such as providing nutrients and vitamins and in Phase I and Phase II drug metabolism. The human gut microbiota is represented mainly by Firmicutes and Bacteroidetes and to a lesser degree by Actinobacteria and Proteobacteria, with each individual harbouring at least 160 such species. Gut microbiota contributes to blood pressure homeostasis and the pathogenesis of arterial hypertension through production, modification and degradation of a variety of microbial-derived bioactive metabolites. Animal studies and to a lesser degree human research has unmasked relative mechanisms, mainly through the effect of certain microbiome metabolites and their receptors, outlining this relationship. Interventions to utilize these pathways, with probiotics, prebiotics, antibiotics and fecal microbiome transplantation have shown promising results. Personalized microbiome-based disease prediction and treatment responsiveness seems futuristic. Undoubtedly, a long way of experimental and clinical research should be pursued to elucidate this novel, intriguing and very promising horizon.}, } @article {pmid29881381, year = {2018}, author = {Tsigalou, C and Stavropoulou, E and Bezirtzoglou, E}, title = {Current Insights in Microbiome Shifts in Sjogren's Syndrome and Possible Therapeutic Interventions.}, journal = {Frontiers in immunology}, volume = {9}, number = {}, pages = {1106}, doi = {10.3389/fimmu.2018.01106}, pmid = {29881381}, issn = {1664-3224}, abstract = {Sjogren's syndrome (SS) is an autoimmune disease, among the most common ones, that targets mainly the exocrine glands as well as extra-glandular epithelial tissues. Their lymphocytic infiltration leads to manifestations from other organs (e.g., kidneys, lungs, liver, or thyroid), apart from sicca symptoms (xerostomia and keratoconjunctivitis). SS is more prevalent in women than in men (9:1). Moreover, p.SS patients are in increased risk to develop lymphoma. Certain autoantibodies (e.g., antibodies against ribonucleoprotein autoantigens Ro-SSA and La-SSB) are ultimate hallmarks for the disease. It was not known until recently that culture-independent techniques like next-generation sequencing (NGS) facilitate the study of the microbe communities in humans and scientists achieved to define the outlines of the microbiome contribution in health and disease. Researchers have started to investigate the alterations in diversity of the oral, ocular, or intestinal microbiota in SS. Recent studies indicate that dysbiosis may play a significant role in SS pathogenesis. At the same time, the cause or effect is not clear yet because the dysfunction of salivary glands induces alterations in oral and intestinal microbiome which is linked to worsen of symptoms and disease severity. If the human microbiome proves to play a key role in pathogenesis and manifestation of SS, the next step could be new and promising therapeutic approaches such as probiotics or prebiotics. This mini review focuses on the alterations of microbiome of SS patients, their connection with immune tolerance and new therapeutic strategies involving diet manipulation toward future personalized medicine.}, } @article {pmid29878050, year = {2018}, author = {Albayrak, L and Khanipov, K and Golovko, G and Fofanov, Y}, title = {Detection of Multidimensional Co-Exclusion Patterns in Microbial Communities.}, journal = {Bioinformatics (Oxford, England)}, volume = {}, number = {}, pages = {}, doi = {10.1093/bioinformatics/bty414}, pmid = {29878050}, issn = {1367-4811}, abstract = {Motivation: Identification of complex relationships among members of microbial communities is key to understand and control the microbiota. Co-exclusion is arguably one of the most important patterns reflecting microorganisms' intolerance to each other's presence. Knowing these relations opens an opportunity to manipulate microbiotas, personalize anti-microbial and probiotic treatments as well as guide microbiota transplantation. The co-exclusion pattern however, cannot be appropriately described by a linear function nor its strength be estimated using covariance or (negative) Pearson and Spearman correlation coefficients. This manuscript proposes a way to quantify the strength and evaluate the statistical significance of co-exclusion patterns between two, three or more variables describing a microbiota and allows one to extend analysis beyond microorganism abundance by including other microbiome associated measurements such as, pH, temperature etc., as well as estimate the expected numbers of false positive co-exclusion patterns in a co-exclusion network.

Results: The implemented computational pipeline (CoEx) tested against 2,380 microbial profiles (samples) from The Human Microbiome Project resulted in body-site specific pairwise co-exclusion patterns.

Availability: C++ source code for calculation of the score and p-value for 2, 3, and 4 dimensional co-exclusion patterns as well as source code and executable files for the CoEx pipeline are available at https://scsb.utmb.edu/labgroups/fofanov/co-exclusion_in_microbial_communities.asp.

Contact: lealbayr@utmb.edu.

Supplementary information: Supplementary data are available at Bioinformatics online.}, } @article {pmid29875143, year = {2018}, author = {Wandro, S and Osborne, S and Enriquez, C and Bixby, C and Arrieta, A and Whiteson, K}, title = {The Microbiome and Metabolome of Preterm Infant Stool Are Personalized and Not Driven by Health Outcomes, Including Necrotizing Enterocolitis and Late-Onset Sepsis.}, journal = {mSphere}, volume = {3}, number = {3}, pages = {}, doi = {10.1128/mSphere.00104-18}, pmid = {29875143}, issn = {2379-5042}, support = {U24 DK097154/DK/NIDDK NIH HHS/United States ; }, abstract = {The assembly and development of the gut microbiome in infants have important consequences for immediate and long-term health. Preterm infants represent an abnormal case for bacterial colonization because of early exposure to bacteria and frequent use of antibiotics. To better understand the assembly of the gut microbiota in preterm infants, fecal samples were collected from 32 very low birth weight preterm infants over the first 6 weeks of life. Infant health outcomes included health, late-onset sepsis, and necrotizing enterocolitis (NEC). We characterized bacterial compositions by 16S rRNA gene sequencing and metabolomes by untargeted gas chromatography-mass spectrometry. Preterm infant fecal samples lacked beneficial Bifidobacterium spp. and were dominated by Enterobacteriaceae, Enterococcus, and Staphylococcus organisms due to nearly uniform antibiotic administration. Most of the variance between the microbial community compositions could be attributed to the baby from which the sample derived (permutational multivariate analysis of variance [PERMANOVA] R2 = 0.48, P < 0.001), while clinical status (health, NEC, or late-onset sepsis) and overlapping times in the neonatal intensive care unit (NICU) did not explain a significant amount of variation in bacterial composition. Fecal metabolomes were also found to be unique to the individual (PERMANOVA R2 = 0.43, P < 0.001) and weakly associated with bacterial composition (Mantel statistic r = 0.23 ± 0.05, P < 0.05). No measured metabolites were found to be associated with necrotizing enterocolitis, late-onset sepsis, or a healthy outcome. Overall, preterm infant gut microbial communities were personalized and reflected antibiotic usage.IMPORTANCE Preterm infants face health problems likely related to microbial exposures, including sepsis and necrotizing enterocolitis. However, the role of the gut microbiome in preterm infant health is poorly understood. Microbial colonization differs from that of healthy term babies because it occurs in the NICU and is often perturbed by antibiotics. We measured bacterial compositions and metabolomic profiles of 77 fecal samples from 32 preterm infants to investigate the differences between microbiomes in health and disease. Rather than finding microbial signatures of disease, we found that both the preterm infant microbiome and the metabolome were personalized and that the preterm infant gut microbiome is enriched in microbes that commonly dominate in the presence of antibiotics. These results contribute to the growing knowledge of the preterm infant microbiome and emphasize that a personalized view will be important to disentangle the health consequences of the preterm infant microbiome.}, } @article {pmid29870114, year = {2018}, author = {Chin-Yee, B and Subramanian, SV and Verma, AA and Laupacis, A and Razak, F}, title = {Emerging Trends in Clinical Research: With Implications for Population Health and Health Policy.}, journal = {The Milbank quarterly}, volume = {96}, number = {2}, pages = {369-401}, doi = {10.1111/1468-0009.12328}, pmid = {29870114}, issn = {1468-0009}, mesh = {Clinical Nursing Research/*trends ; Clinical Trials as Topic/*statistics & numerical data ; Forecasting ; Health Equity/*trends ; Health Policy/*trends ; Humans ; Population Health/*statistics & numerical data ; }, abstract = {Policy Points: Significant advances in clinical medicine that have broader societal relevance may be less accessible to population health researchers and policymakers because of increased specialization within fields. We describe important recent clinical advances and discuss their broader societal impact. These advances include more expansive strategies for disease prevention, the rise of precision medicine, applications of human microbiome research, and new and highly successful treatments for hepatitis C infection. These recent developments in clinical research raise important issues surrounding health care costs and equitable resource allocation that necessitate an ongoing dialogue among the fields of clinical medicine, population health, and health policy.

CONTEXT: Developments in clinical medicine have important implications for population health, and there is a need for interdisciplinary engagement among clinical medicine, the social sciences, and public health research. The aim of this article is to help bridge the divide between these fields by exploring major recent advances in clinical medicine that have important implications for population health.

METHODS: We reviewed the most cited articles published from 2010 to 2015 in 5 high-impact clinical journals and selected 5 randomized controlled trials and 2 related clinical practice guidelines that are broadly relevant to population health and policy.

FINDINGS: We discuss the following themes: (1) expanding indications for drug therapy and the inherent medicalization of the population as highlighted by studies and clinical guidelines supporting lower blood pressure targets or widespread statin use; (2) the tension in nutritional research between quantifying the impact of isolated nutrients and studying specific foods and dietary patterns, for example, the role of the Mediterranean diet in the primary prevention of cardiovascular disease; (3) the issue of high medication costs and the challenge of providing equitable access raised by the development of new and effective treatments for hepatitis C infection; (4) emerging clinical applications of research on the human microbiome as illustrated by fecal transplant to treat Clostridium difficile infections; and (5) the promise and limitations of precision medicine as demonstrated by the rise of novel targeted therapies in oncology.

CONCLUSIONS: These developments in clinical science hold promise for improving individual and population health and raise important questions about resource allocation, the role of prevention, and health disparities.}, } @article {pmid29868846, year = {2018}, author = {Sankaran, K and Holmes, SP}, title = {Latent variable modeling for the microbiome.}, journal = {Biostatistics (Oxford, England)}, volume = {}, number = {}, pages = {}, doi = {10.1093/biostatistics/kxy018}, pmid = {29868846}, issn = {1468-4357}, abstract = {The human microbiome is a complex ecological system, and describing its structure and function under different environmental conditions is important from both basic scientific and medical perspectives. Viewed through a biostatistical lens, many microbiome analysis goals can be formulated as latent variable modeling problems. However, although probabilistic latent variable models are a cornerstone of modern unsupervised learning, they are rarely applied in the context of microbiome data analysis, in spite of the evolutionary, temporal, and count structure that could be directly incorporated through such models. We explore the application of probabilistic latent variable models to microbiome data, with a focus on Latent Dirichlet allocation, Non-negative matrix factorization, and Dynamic Unigram models. To develop guidelines for when different methods are appropriate, we perform a simulation study. We further illustrate and compare these techniques using the data of Dethlefsen and Relman (2011, Incomplete recovery and individualized responses of the human distal gut microbiota to repeated antibiotic perturbation. Proceedings of the National Academy of Sciences108, 4554-4561), a study on the effects of antibiotics on bacterial community composition. Code and data for all simulations and case studies are available publicly.}, } @article {pmid29868514, year = {2018}, author = {Chai, Q and Zhang, Y and Liu, CH}, title = {Mycobacterium tuberculosis: An Adaptable Pathogen Associated With Multiple Human Diseases.}, journal = {Frontiers in cellular and infection microbiology}, volume = {8}, number = {}, pages = {158}, doi = {10.3389/fcimb.2018.00158}, pmid = {29868514}, issn = {2235-2988}, abstract = {Mycobacterium tuberculosis, the etiological agent of tuberculosis (TB), is an extremely successful pathogen that adapts to survive within the host. During the latency phase of infection, M. tuberculosis employs a range of effector proteins to be cloud the host immune system and shapes its lifestyle to reside in granulomas, sophisticated, and organized structures of immune cells that are established by the host in response to persistent infection. While normally being restrained in immunocompetent hosts, M. tuberculosis within granulomas can cause the recrudescence of TB when host immunity is compromised. Aside from causing TB, accumulating evidence suggests that M. tuberculosis is also associated with multiple other human diseases, such as pulmonary complications, autoimmune diseases, and metabolic syndromes. Furthermore, it has been recently appreciated that M. tuberculosis infection can also reciprocally interact with the human microbiome, which has a strong link to immune balance and health. In this review, we highlight the adaptive survival of M. tuberculosis within the host and provide an overview for regulatory mechanisms underlying interactions between M. tuberculosis infection and multiple important human diseases. A better understanding of how M. tuberculosis regulates the host immune system to cause TB and reciprocally regulates other human diseases is critical for developing rational treatments to better control TB and help alleviate its associated comorbidities.}, } @article {pmid29844606, year = {2018}, author = {Reid, G}, title = {What are bacteria doing in the bladder?.}, journal = {Nature reviews. Urology}, volume = {15}, number = {8}, pages = {469-470}, doi = {10.1038/s41585-018-0032-y}, pmid = {29844606}, issn = {1759-4820}, } @article {pmid29802603, year = {2018}, author = {Stefano, GB and Pilonis, N and Ptacek, R and Raboch, J and Vnukova, M and Kream, RM}, title = {Gut, Microbiome, and Brain Regulatory Axis: Relevance to Neurodegenerative and Psychiatric Disorders.}, journal = {Cellular and molecular neurobiology}, volume = {38}, number = {6}, pages = {1197-1206}, doi = {10.1007/s10571-018-0589-2}, pmid = {29802603}, issn = {1573-6830}, abstract = {It has become apparent that the molecular and biochemical integrity of interactive families, genera, and species of human gut microflora is critically linked to maintaining complex metabolic and behavioral processes mediated by peripheral organ systems and central nervous system neuronal groupings. Relatively recent studies have established intrinsic ratios of enterotypes contained within the human microbiome across demographic subpopulations and have empirically linked significant alterations in the expression of bacterial enterotypes with the initiation and persistence of several major metabolic and psychiatric disorders. Accordingly, the goal of our review is to highlight potential thematic/functional linkages of pathophysiological alterations in gut microbiota and bidirectional gut-brain signaling pathways with special emphasis on the potential roles of gut dysbiosis on the pathophysiology of psychiatric illnesses. We provide critical discussion of putative thematic linkages of Parkinson's disease (PD) data sets to similar pathophysiological events as potential causative factors in the development and persistence of diverse psychiatric illnesses. Finally, we include a concise review of preclinical paradigms that involve immunologically-induced GI deficits and dysbiosis of maternal microflora that are functionally linked to impaired neurodevelopmental processes leading to affective behavioral syndromes in the offspring.}, } @article {pmid29795809, year = {2018}, author = {McDonald, D and Hyde, E and Debelius, JW and Morton, JT and Gonzalez, A and Ackermann, G and Aksenov, AA and Behsaz, B and Brennan, C and Chen, Y and DeRight Goldasich, L and Dorrestein, PC and Dunn, RR and Fahimipour, AK and Gaffney, J and Gilbert, JA and Gogul, G and Green, JL and Hugenholtz, P and Humphrey, G and Huttenhower, C and Jackson, MA and Janssen, S and Jeste, DV and Jiang, L and Kelley, ST and Knights, D and Kosciolek, T and Ladau, J and Leach, J and Marotz, C and Meleshko, D and Melnik, AV and Metcalf, JL and Mohimani, H and Montassier, E and Navas-Molina, J and Nguyen, TT and Peddada, S and Pevzner, P and Pollard, KS and Rahnavard, G and Robbins-Pianka, A and Sangwan, N and Shorenstein, J and Smarr, L and Song, SJ and Spector, T and Swafford, AD and Thackray, VG and Thompson, LR and Tripathi, A and Vázquez-Baeza, Y and Vrbanac, A and Wischmeyer, P and Wolfe, E and Zhu, Q and , and Knight, R}, title = {American Gut: an Open Platform for Citizen Science Microbiome Research.}, journal = {mSystems}, volume = {3}, number = {3}, pages = {}, doi = {10.1128/mSystems.00031-18}, pmid = {29795809}, issn = {2379-5077}, support = {//Wellcome Trust/United Kingdom ; P30 DK042086/DK/NIDDK NIH HHS/United States ; P30 DK043351/DK/NIDDK NIH HHS/United States ; }, abstract = {Although much work has linked the human microbiome to specific phenotypes and lifestyle variables, data from different projects have been challenging to integrate and the extent of microbial and molecular diversity in human stool remains unknown. Using standardized protocols from the Earth Microbiome Project and sample contributions from over 10,000 citizen-scientists, together with an open research network, we compare human microbiome specimens primarily from the United States, United Kingdom, and Australia to one another and to environmental samples. Our results show an unexpected range of beta-diversity in human stool microbiomes compared to environmental samples; demonstrate the utility of procedures for removing the effects of overgrowth during room-temperature shipping for revealing phenotype correlations; uncover new molecules and kinds of molecular communities in the human stool metabolome; and examine emergent associations among the microbiome, metabolome, and the diversity of plants that are consumed (rather than relying on reductive categorical variables such as veganism, which have little or no explanatory power). We also demonstrate the utility of the living data resource and cross-cohort comparison to confirm existing associations between the microbiome and psychiatric illness and to reveal the extent of microbiome change within one individual during surgery, providing a paradigm for open microbiome research and education. IMPORTANCE We show that a citizen science, self-selected cohort shipping samples through the mail at room temperature recaptures many known microbiome results from clinically collected cohorts and reveals new ones. Of particular interest is integrating n = 1 study data with the population data, showing that the extent of microbiome change after events such as surgery can exceed differences between distinct environmental biomes, and the effect of diverse plants in the diet, which we confirm with untargeted metabolomics on hundreds of samples.}, } @article {pmid29795140, year = {2018}, author = {Porter, CM and Shrestha, E and Peiffer, LB and Sfanos, KS}, title = {The microbiome in prostate inflammation and prostate cancer.}, journal = {Prostate cancer and prostatic diseases}, volume = {21}, number = {3}, pages = {345-354}, doi = {10.1038/s41391-018-0041-1}, pmid = {29795140}, issn = {1476-5608}, abstract = {BACKGROUND: The human microbiome may influence prostate cancer initiation and/or progression through both direct and indirect interactions. To date, the majority of studies have focused on direct interactions including the influence of prostate infections on prostate cancer risk and, more recently, on the composition of the urinary microbiome in relation to prostate cancer. Less well understood are indirect interactions of the microbiome with prostate cancer, such as the influence of the gastrointestinal or oral microbiota on pro- or anti-carcinogenic xenobiotic metabolism, and treatment response.

METHODS: We review the literature to date on direct and indirect interactions of the microbiome with prostate inflammation and prostate cancer.

RESULTS: Emerging studies indicate that the microbiome can influence prostate inflammation in relation to benign prostate conditions such as prostatitis/chronic pelvic pain syndrome and benign prostatic hyperplasia, as well as in prostate cancer. We provide evidence that the human microbiome present at multiple anatomic sites (urinary tract, gastrointestinal tract, oral cavity, etc.) may play an important role in prostate health and disease.

CONCLUSIONS: In health, the microbiome encourages homeostasis and helps educate the immune system. In dysbiosis, a systemic inflammatory state may be induced, predisposing remote anatomical sites to disease, including cancer. The microbiome's ability to affect systemic hormone levels may also be important, particularly in a disease such as prostate cancer that is dually affected by estrogen and androgen levels. Due to the complexity of the potential interconnectedness between prostate cancer and the microbiome, it is vital to further explore and understand the relationships that are involved.}, } @article {pmid29789680, year = {2018}, author = {Banerjee, S and Schlaeppi, K and van der Heijden, MGA}, title = {Keystone taxa as drivers of microbiome structure and functioning.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {9}, pages = {567-576}, doi = {10.1038/s41579-018-0024-1}, pmid = {29789680}, issn = {1740-1534}, abstract = {Microorganisms have a pivotal role in the functioning of ecosystems. Recent studies have shown that microbial communities harbour keystone taxa, which drive community composition and function irrespective of their abundance. In this Opinion article, we propose a definition of keystone taxa in microbial ecology and summarize over 200 microbial keystone taxa that have been identified in soil, plant and marine ecosystems, as well as in the human microbiome. We explore the importance of keystone taxa and keystone guilds for microbiome structure and functioning and discuss the factors that determine their distribution and activities.}, } @article {pmid29786923, year = {2018}, author = {Bandara, HMHN and Panduwawala, CP and Samaranayake, LP}, title = {Biodiversity of the human oral mycobiome in health and disease.}, journal = {Oral diseases}, volume = {}, number = {}, pages = {}, doi = {10.1111/odi.12899}, pmid = {29786923}, issn = {1601-0825}, abstract = {The organisms that colonize the human body over a lifetime are diverse, extensive and gargantuan. A fair proportion of the microbiota that constitutes this human microbiome live within our oral cavities mostly as harmonious associates causing only sporadic disease. An important core constituent of the microbiome is the mycobiome, representing various fungal genera. Up until recently, only a few species of fungi, mainly Candida species, were thought to constitute the human oral mycobiome. The reasons for this are manifold, although the uncultivable nature of many fungi in conventional laboratory media, and their complex genetic composition seem to be the major factors which eluded their detection over the years. Nevertheless, recent advances in computing and high-throughput sequencing such as next-generation sequencing (NGS) platforms have provided us a panoramic view of a totally new world of fungi that are human oral cohabitués. Their diversity is perplexing, and functionality yet to be deciphered. Here, we provide a glimpse of what is currently known of the oral mycobiome, in health and disease, with some future perspectives.}, } @article {pmid29781826, year = {2018}, author = {Swami, U and Zakharia, Y and Zhang, J}, title = {Understanding Microbiome Effect on Immune Checkpoint Inhibition in Lung Cancer: Placing the Puzzle Pieces Together.}, journal = {Journal of immunotherapy (Hagerstown, Md. : 1997)}, volume = {41}, number = {8}, pages = {359-360}, doi = {10.1097/CJI.0000000000000232}, pmid = {29781826}, issn = {1537-4513}, support = {P30 CA086862/CA/NCI NIH HHS/United States ; }, abstract = {Over the past couple of years, human microbiome has received increasing attention as a regulator and predictor of response to the therapies of various diseases. It is speculated that manipulating gut microbiome can modify response to cancer immunotherapies as well. Through this review, we have critically analyzed our current understanding of gut microbiome as a modulator of immunotherapies in lung cancer, explained conflicting data, evaluated current gaps and extrapolated our present knowledge to generate directions for future investigations.}, } @article {pmid29773467, year = {2018}, author = {Daliri, EB and Tango, CN and Lee, BH and Oh, DH}, title = {Human microbiome restoration and safety.}, journal = {International journal of medical microbiology : IJMM}, volume = {308}, number = {5}, pages = {487-497}, doi = {10.1016/j.ijmm.2018.05.002}, pmid = {29773467}, issn = {1618-0607}, mesh = {Anti-Bacterial Agents ; Bacteria/classification/isolation & purification ; Diet ; Dysbiosis/*therapy ; Fecal Microbiota Transplantation/*adverse effects/methods ; Gastrointestinal Microbiome/*physiology ; Humans ; Probiotics/*administration & dosage ; }, abstract = {The human gut microbiome consists of many bacteria which are in symbiotic relationship with human beings. The gut microbial metabolism, as well as the microbial-host co-metabolism, has been found to greatly influence health and disease. Factors such as diet, antibiotic use and lifestyle have been associated with alterations in the gut microbial community and may result in several pathological conditions. For this reason, several strategies including fecal microbiota transplant and probiotic administration have been applied and proven to be feasible and effective in restoring the gut microbiota in humans. Yet, safety concerns such as potential health risks that may arise from such interventions and how these strategies are regulated need to be addressed. Also, it will be important to know if these microbiome restoration strategies can have a profound impact on health. This review provides an overview of our current knowledge of the microbiome restoration strategies and safety issues on how these strategies are regulated.}, } @article {pmid29765359, year = {2018}, author = {Ingala, MR and Simmons, NB and Wultsch, C and Krampis, K and Speer, KA and Perkins, SL}, title = {Comparing Microbiome Sampling Methods in a Wild Mammal: Fecal and Intestinal Samples Record Different Signals of Host Ecology, Evolution.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {803}, doi = {10.3389/fmicb.2018.00803}, pmid = {29765359}, issn = {1664-302X}, abstract = {The gut microbiome is a community of host-associated symbiotic microbes that fulfills multiple key roles in host metabolism, immune function, and tissue development. Given the ability of the microbiome to impact host fitness, there is increasing interest in studying the microbiome of wild animals to better understand these communities in the context of host ecology and evolution. Human microbiome research protocols are well established, but wildlife microbiome research is still a developing field. Currently, there is no standardized set of best practices guiding the collection of microbiome samples from wildlife. Gut microflora are typically sampled either by fecal collection, rectal swabbing, or by destructively sampling the intestinal contents of the host animal. Studies rarely include more than one sampling technique and no comparison of these methods currently exists for a wild mammal. Although some studies have hypothesized that the fecal microbiome is a nested subset of the intestinal microbiome, this hypothesis has not been formally tested. To address these issues, we examined guano (feces) and distal intestinal mucosa from 19 species of free-ranging bats from Lamanai, Belize, using 16S rRNA amplicon sequencing to compare microbial communities across sample types. We found that the diversity and composition of intestine and guano samples differed substantially. In addition, we conclude that signatures of host evolution are retained by studying gut microbiomes based on mucosal tissue samples, but not fecal samples. Conversely, fecal samples retained more signal of host diet than intestinal samples. These results suggest that fecal and intestinal sampling methods are not interchangeable, and that these two microbiotas record different information about the host from which they are isolated.}, } @article {pmid29760467, year = {2018}, author = {Xian, P and Xuedong, Z and Xin, X and Yuqing, L and Yan, L and Jiyao, L and Xiaoquan, S and Shi, H and Jian, X and Ga, L}, title = {The Oral Microbiome Bank of China.}, journal = {International journal of oral science}, volume = {10}, number = {2}, pages = {16}, doi = {10.1038/s41368-018-0018-x}, pmid = {29760467}, issn = {2049-3169}, abstract = {The human microbiome project (HMP) promoted further understanding of human oral microbes. However, research on the human oral microbiota has not made as much progress as research on the gut microbiota. Currently, the causal relationship between the oral microbiota and oral diseases remains unclear, and little is known about the link between the oral microbiota and human systemic diseases. To further understand the contribution of the oral microbiota in oral diseases and systemic diseases, a Human Oral Microbiome Database (HOMD) was established in the US. The HOMD includes 619 taxa in 13 phyla, and most of the microorganisms are from American populations. Due to individual differences in the microbiome, the HOMD does not reflect the Chinese oral microbial status. Herein, we established a new oral microbiome database-the Oral Microbiome Bank of China (OMBC, http://www.sklod.org/ombc). Currently, the OMBC includes information on 289 bacterial strains and 720 clinical samples from the Chinese population, along with lab and clinical information. The OMBC is the first curated description of a Chinese-associated microbiome; it provides tools for use in investigating the role of the oral microbiome in health and diseases, and will give the community abundant data and strain information for future oral microbial studies.}, } @article {pmid29756665, year = {2018}, author = {Watson, E and Reid, G}, title = {Metabolomics as a clinical testing method for the diagnosis of vaginal dysbiosis.}, journal = {American journal of reproductive immunology (New York, N.Y. : 1989)}, volume = {80}, number = {2}, pages = {e12979}, doi = {10.1111/aji.12979}, pmid = {29756665}, issn = {1600-0897}, abstract = {Microbes play an important role in vaginal health, with lactobacilli a particularly abundant species. When dysbiosis occurs, the tools to determine whether it is a condition such as bacterial vaginosis, and whether it warrants antibiotic treatment, are currently suboptimal. We propose that standardization and implementation of an affordable metabolomics-based diagnostic technique could reduce instances of false positives, stress associated with misdiagnosis, and potentially save time and money. Basing diagnosis on the detection of pH elevated above 4.5 and specific polyamines could provide a better method to assist a physician determine whether treatment is warranted.}, } @article {pmid29756604, year = {2018}, author = {Stefano, GB and Kream, RM}, title = {Alkaloids, Nitric Oxide, and Nitrite Reductases: Evolutionary Coupling as Key Regulators of Cellular Bioenergetics with Special Relevance to the Human Microbiome.}, journal = {Medical science monitor : international medical journal of experimental and clinical research}, volume = {24}, number = {}, pages = {3153-3158}, doi = {10.12659/MSM.909409}, pmid = {29756604}, issn = {1643-3750}, mesh = {Alkaloids/*metabolism ; *Biological Evolution ; *Energy Metabolism ; Humans ; *Microbiota ; Nitric Oxide/*metabolism ; Nitrite Reductases/*metabolism ; }, abstract = {Typical alkaloids expressed by prokaryotic and eukaryotic cells are small heterocyclic compounds containing weakly basic nitrogen groups that are critically important for mediating essential biological activities. The prototype opiate alkaloid morphine represents a low molecular mass heterocyclic compound that has been evolutionarily fashioned from a relatively restricted role as a secreted antimicrobial phytoalexin into a broad spectrum regulatory molecule. As an essential corollary, positive evolutionary pressure has driven the development of a cognate 6-transmembrane helical (TMH) domain μ3 opiate receptor that is exclusively responsive to morphine and related opiate alkaloids. A key aspect of "morphinergic" signaling mediated by μ3 opiate receptor activation is its functional coupling with regulatory pathways utilizing constitutive nitric oxide (NO) as a signaling molecule. Importantly, tonic and phasic intra-mitochondrial NO production exerts profound inhibitory effects on the rate of electron transport, H+ pumping, and O2 consumption. Given the pluripotent role of NO as a selective, temporally-defined chemical regulator of mitochondrial respiration and cellular bioenergetics, the expansion of prokaryotic denitrification systems into mitochondrial NO/nitrite cycling complexes represents a series of evolutionary modifications of existential proportions. Presently, our short review provides selective discussion of evolutionary development of morphine, opiate alkaloids, μ3 opiate receptors, and NO systems, within the perspectives of enhanced mitochondrial function, cellular bioenergetics, and the human microbiome.}, } @article {pmid29753695, year = {2018}, author = {Chu, DM and Seferovic, M and Pace, RM and Aagaard, KM}, title = {The microbiome in preterm birth.}, journal = {Best practice & research. Clinical obstetrics & gynaecology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.bpobgyn.2018.03.006}, pmid = {29753695}, issn = {1532-1932}, abstract = {The microbiome is thought to play a role in the maintenance of a healthy pregnancy and thus may either contribute to or protect from preterm birth. Study of the human microbiome has been aided by metagenomic sequencing approaches, providing greater insight into the commensal bacteria that coexist in and on our bodies. The vaginal microbiome has been the most widely studied, though there have been recent efforts to explore the gut, cervical-vaginal, placental and oral microbiomes in the further search of etiologies of preterm birth. To date, a specific microbiome community or microorganism has yet to be reliably associated with preterm birth. This is partly due to the fact that the 'normal' constituents' microbiome can vary widely between healthy individuals. Before our knowledge of the microbiome can be utilized and applied in clinical practice, a greater understanding of the 'healthy' microbiome must be achieved. In particular, we must first appreciate how our microbes influence our biology to promote a healthy pregnancy or alternately render preterm birth.}, } @article {pmid29747892, year = {2018}, author = {Valentine, G and Chu, DM and Stewart, CJ and Aagaard, KM}, title = {Relationships Between Perinatal Interventions, Maternal-Infant Microbiomes, and Neonatal Outcomes.}, journal = {Clinics in perinatology}, volume = {45}, number = {2}, pages = {339-355}, doi = {10.1016/j.clp.2018.01.008}, pmid = {29747892}, issn = {1557-9840}, abstract = {The human microbiome acquires its vastness and diversity over a relatively short time period during development. Much is unknown, however, about the precise prenatal versus postnatal timing or its sources and determinants. Given early evidence of a role for influences during pregnancy and early neonatal and infant life on the microbiome and subsequent metabolic health, research investigating the development and shaping of the microbiome in the fetus and neonate is an important arena for study. This article reviews the relevant available literature and future questions on what shapes the microbiome during early development and mechanisms for doing so.}, } @article {pmid29743478, year = {2018}, author = {Olde Loohuis, LM and Mangul, S and Ori, APS and Jospin, G and Koslicki, D and Yang, HT and Wu, T and Boks, MP and Lomen-Hoerth, C and Wiedau-Pazos, M and Cantor, RM and de Vos, WM and Kahn, RS and Eskin, E and Ophoff, RA}, title = {Transcriptome analysis in whole blood reveals increased microbial diversity in schizophrenia.}, journal = {Translational psychiatry}, volume = {8}, number = {1}, pages = {96}, doi = {10.1038/s41398-018-0107-9}, pmid = {29743478}, issn = {2158-3188}, abstract = {The role of the human microbiome in health and disease is increasingly appreciated. We studied the composition of microbial communities present in blood across 192 individuals, including healthy controls and patients with three disorders affecting the brain: schizophrenia, amyotrophic lateral sclerosis, and bipolar disorder. By using high-quality unmapped RNA sequencing reads as candidate microbial reads, we performed profiling of microbial transcripts detected in whole blood. We were able to detect a wide range of bacterial and archaeal phyla in blood. Interestingly, we observed an increased microbial diversity in schizophrenia patients compared to the three other groups. We replicated this finding in an independent schizophrenia case-control cohort. This increased diversity is inversely correlated with estimated cell abundance of a subpopulation of CD8+ memory T cells in healthy controls, supporting a link between microbial products found in blood, immunity and schizophrenia.}, } @article {pmid29743119, year = {2018}, author = {Zolfo, M and Asnicar, F and Manghi, P and Pasolli, E and Tett, A and Segata, N}, title = {Profiling microbial strains in urban environments using metagenomic sequencing data.}, journal = {Biology direct}, volume = {13}, number = {1}, pages = {9}, doi = {10.1186/s13062-018-0211-z}, pmid = {29743119}, issn = {1745-6150}, abstract = {BACKGROUND: The microbial communities populating human and natural environments have been extensively characterized with shotgun metagenomics, which provides an in-depth representation of the microbial diversity within a sample. Microbes thriving in urban environments may be crucially important for human health, but have received less attention than those of other environments. Ongoing efforts started to target urban microbiomes at a large scale, but the most recent computational methods to profile these metagenomes have never been applied in this context. It is thus currently unclear whether such methods, that have proven successful at distinguishing even closely related strains in human microbiomes, are also effective in urban settings for tasks such as cultivation-free pathogen detection and microbial surveillance. Here, we aimed at a) testing the currently available metagenomic profiling tools on urban metagenomics; b) characterizing the organisms in urban environment at the resolution of single strain and c) discussing the biological insights that can be inferred from such methods.

RESULTS: We applied three complementary methods on the 1614 metagenomes of the CAMDA 2017 challenge. With MetaMLST we identified 121 known sequence-types from 15 species of clinical relevance. For instance, we identified several Acinetobacter strains that were close to the nosocomial opportunistic pathogen A. nosocomialis. With StrainPhlAn, a generalized version of the MetaMLST approach, we inferred the phylogenetic structure of Pseudomonas stutzeri strains and suggested that the strain-level heterogeneity in environmental samples is higher than in the human microbiome. Finally, we also probed the functional potential of the different strains with PanPhlAn. We further showed that SNV-based and pangenome-based profiling provide complementary information that can be combined to investigate the evolutionary trajectories of microbes and to identify specific genetic determinants of virulence and antibiotic resistances within closely related strains.

CONCLUSION: We show that strain-level methods developed primarily for the analysis of human microbiomes can be effective for city-associated microbiomes. In fact, (opportunistic) pathogens can be tracked and monitored across many hundreds of urban metagenomes. However, while more effort is needed to profile strains of currently uncharacterized species, this work poses the basis for high-resolution analyses of microbiomes sampled in city and mass transportation environments.

REVIEWERS: This article was reviewed by Alexandra Bettina Graf, Daniel Huson and Trevor Cickovski.}, } @article {pmid29739953, year = {2018}, author = {Ma, ZS}, title = {Diversity time-period and diversity-time-area relationships exemplified by the human microbiome.}, journal = {Scientific reports}, volume = {8}, number = {1}, pages = {7214}, doi = {10.1038/s41598-018-24881-3}, pmid = {29739953}, issn = {2045-2322}, abstract = {We extend the ecological laws of species-time relationship (STR) and species-time-area relationship (STAR) to general diversity time-period relationship (DTR) and diversity-time-area relationship (DTAR), and test the extensions with the human vaginal microbiome datasets by building 1460 DTR/DTAR models. Our extensions were inspired by the observation that Hill numbers, well regarded as the most appropriate measure of alpha-diversity and also particularly suitable for multiplicative beta-diversity partitioning, are actually in the units of effective species, and therefore, should be able to substitute for species in the STR and STAR. We found that the traditional power law (PL) model is only applicable for DTR at diversity order zero (i.e., species richness); at higher diversity orders (q = 1-4), the power law with exponent cutoff (PLEC) and power law with inverse exponent cutoff (PLIEC) are more appropriate. In particular, PLEC has an advantage over PLIEC in predicting maximal accumulation diversity (MAD) over time. In fact, with the DTR extensions, we can construct DTR and MAD profiles. To the best of our knowledge, this is the first comprehensive investigation of the DTR/DTAR in human microbiome. Methodologically, our DTR/DTAR profiles can characterize general diversity scaling beyond species richness, covering both alpha- and beta-diversity regimes across different diversity orders.}, } @article {pmid29737047, year = {2018}, author = {Zhao, N and Zhan, X and Guthrie, KA and Mitchell, CM and Larson, J}, title = {Generalized Hotelling's test for paired compositional data with application to human microbiome studies.}, journal = {Genetic epidemiology}, volume = {42}, number = {5}, pages = {459-469}, doi = {10.1002/gepi.22127}, pmid = {29737047}, issn = {1098-2272}, mesh = {Computer Simulation ; Databases as Topic ; Female ; Humans ; *Microbiota ; *Models, Genetic ; Postmenopause ; Vagina/microbiology ; }, abstract = {The human microbiome is a dynamic system that changes due to diseases, medication, change in diet, etc. The paired design is a common approach to evaluate the microbial changes while controlling for the inherent differences between people. For example, microbiome data may be collected from the same individuals before and after a treatment. Two challenges exist in analyzing this type of data. First, microbiome data are compositional such that the reads for all taxa in each sample are constrained to sum to a constant. Second, the number of taxa can be much larger than the sample size. Few statistical methods exist to analyze such data besides methods that test one taxon at a time. In this paper, we propose to first conduct a log-ratio transformation of the compositions, and then develop a generalized Hotelling's test (GHT) to evaluate whether the average microbiome compositions are equivalent in the paired samples. We replace the sample covariance matrix in standard Hotelling's statistic by a shrinkage-based covariance, calculated as a weighted average of the sample covariance and a positive definite target matrix. The optimal weighting can be obtained for many commonly used target matrices. We develop a permutation procedure to assess the statistical significance. Extensive simulations show that our proposed method has well-controlled type I error and better power than a few ad hoc approaches. We apply our method to examine the vaginal microbiome changes in response to treatments for menopausal hot flashes. An R package " GHT" is freely available at https://github.com/zhaoni153/GHT.}, } @article {pmid29728386, year = {2018}, author = {Feng, S and Bootsma, M and McLellan, SL}, title = {Human-Associated Lachnospiraceae Genetic Markers Improve Detection of Fecal Pollution Sources in Urban Waters.}, journal = {Applied and environmental microbiology}, volume = {84}, number = {14}, pages = {}, doi = {10.1128/AEM.00309-18}, pmid = {29728386}, issn = {1098-5336}, support = {R01 AI091829/AI/NIAID NIH HHS/United States ; }, abstract = {The human microbiome contains many organisms that could potentially be used as indicators of human fecal pollution. Here we report the development of two novel human-associated genetic marker assays that target organisms within the family Lachnospiraceae Next-generation sequencing of the V6 region of the 16S rRNA gene from sewage and animal stool samples identified 40 human-associated marker candidates with a robust signal in sewage and low or no occurrence in samples from nonhuman hosts. Two were chosen for quantitative PCR (qPCR) assay development using longer sequences (the V2 to V9 regions) generated from clone libraries. Validation of these assays with these markers, designated Lachno3 and Lachno12, was performed using fecal samples (n = 55) from cat, dog, pig, cow, deer, and gull sources, and the results were compared with those of established host-associated assays (the Lachno2 marker and two human Bacteroides markers, the HB and HF183/BacR287). Each of the established assays cross-reacted with samples from at least one other animal species, including animals common in urban areas. The Lachno3 and Lachno12 markers were primarily human associated; however, the Lachno12 marker demonstrated low levels of cross-reactivity with samples from select cows and nonspecific amplification with samples from pigs. This limitation may not be problematic when testing urban waters. These novel markers resolved ambiguous results from previous investigations of stormwater-impacted waters, demonstrating their utility. The complexity of the microbiome in humans and animals suggests that no single organism is strictly specific to humans, and the use of multiple complementary markers in combination will provide the highest resolution and specificity for assessing fecal pollution sources.IMPORTANCE Traditional fecal indicator bacteria do not distinguish animal from human fecal pollution, which is necessary to evaluate health risks and mitigate pollution sources. Assessing water in urban areas is challenging, since the water can be impacted by sewage, which has a high likelihood of carrying human pathogens, as well as pet and urban wildlife waste. We demonstrate that the Lachno3 and Lachno12 markers are human associated and highly specific for the detection of human fecal pollution from urban sources, offering reliable identification of fecal pollution sources in urban waters.}, } @article {pmid29725592, year = {2018}, author = {Sigdel, TK and Mercer, N and Nandoe, S and Nicora, CD and Burnum-Johnson, K and Qian, WJ and Sarwal, MM}, title = {Urinary Virome Perturbations in Kidney Transplantation.}, journal = {Frontiers in medicine}, volume = {5}, number = {}, pages = {72}, doi = {10.3389/fmed.2018.00072}, pmid = {29725592}, issn = {2296-858X}, abstract = {The human microbiome is important for health and plays a role in essential metabolic functions and protection from certain pathogens. Conversely, dysbiosis of the microbiome is seen in the context of various diseases. Recent studies have highlighted that a complex microbial community containing hundreds of bacteria colonizes the healthy urinary tract, but little is known about the human urinary viruses in health and disease. To evaluate the human urinary virome in the context of kidney transplantation (tx), variations in the composition of the urinary virome were evaluated in urine samples from normal healthy volunteers as well as patients with kidney disease after they had undergone kidney tx. Liquid chromatography-mass spectrometry/mass spectrometry analysis was undertaken on a selected cohort of 142 kidney tx patients and normal healthy controls, from a larger biobank of 770 kidney biopsy matched urine samples. In addition to analysis of normal healthy control urine, the cohort of kidney tx patients had biopsy confirmed phenotype classification, coincident with the urine sample analyzed, of stable grafts (STA), acute rejection, BK virus nephritis, and chronic allograft nephropathy. We identified 37 unique viruses, 29 of which are being identified for the first time in human urine samples. The composition of the human urinary virome differs in health and kidney injury, and the distribution of viral proteins in the urinary tract may be further impacted by IS exposure, diet and environmental, dietary, or cutaneous exposure to various insecticides and pesticides.}, } @article {pmid29724017, year = {2018}, author = {Avershina, E and Angell, IL and Simpson, M and Storrø, O and Øien, T and Johnsen, R and Rudi, K}, title = {Low Maternal Microbiota Sharing across Gut, Breast Milk and Vagina, as Revealed by 16S rRNA Gene and Reduced Metagenomic Sequencing.}, journal = {Genes}, volume = {9}, number = {5}, pages = {}, doi = {10.3390/genes9050231}, pmid = {29724017}, issn = {2073-4425}, abstract = {The maternal microbiota plays an important role in infant gut colonization. In this work we have investigated which bacterial species are shared across the breast milk, vaginal and stool microbiotas of 109 women shortly before and after giving birth using 16S rRNA gene sequencing and a novel reduced metagenomic sequencing (RMS) approach in a subgroup of 16 women. All the species predicted by the 16S rRNA gene sequencing were also detected by RMS analysis and there was good correspondence between their relative abundances estimated by both approaches. Both approaches also demonstrate a low level of maternal microbiota sharing across the population and RMS analysis identified only two species common to most women and in all sample types (Bifidobacterium longum and Enterococcus faecalis). Breast milk was the only sample type that had significantly higher intra- than inter- individual similarity towards both vaginal and stool samples. We also searched our RMS dataset against an in silico generated reference database derived from bacterial isolates in the Human Microbiome Project. The use of this reference-based search enabled further separation of Bifidobacterium longum into Bifidobacterium longum ssp. longum and Bifidobacterium longum ssp. infantis. We also detected the Lactobacillus rhamnosus GG strain, which was used as a probiotic supplement by some women, demonstrating the potential of RMS approach for deeper taxonomic delineation and estimation.}, } @article {pmid29721973, year = {2018}, author = {Rowan, S and Taylor, A}, title = {The Role of Microbiota in Retinal Disease.}, journal = {Advances in experimental medicine and biology}, volume = {1074}, number = {}, pages = {429-435}, doi = {10.1007/978-3-319-75402-4_53}, pmid = {29721973}, issn = {0065-2598}, abstract = {The ten years since the first publications on the human microbiome project have brought enormous attention and insight into the role of the human microbiome in health and disease. Connections between populations of microbiota and ocular disease are now being established, and increased accessibility to microbiome research and insights into other diseases is expected to yield enormous information in the coming years. With the characterization of the ocular microbiome, important insights have already been made regarding corneal and conjunctival tissues. Roles for non-ocular microbiomes in complex retinal diseases are now being evaluated. For example, the gut microbiome has been implicated in the pathogenesis of uveitis. This short review will summarize the few studies linking gut or oral microbiota to diabetic retinopathy (DR), glaucoma, and age-related macular degeneration (AMD). We will also conjecture where the most significant findings still remain to be elucidated. Finally, we will propose the gut-retina axis, related but distinct from the gut-brain axis.}, } @article {pmid29719941, year = {2018}, author = {Kwan, SE and Shaughnessy, RJ and Hegarty, B and Haverinen-Shaughnessy, U and Peccia, J}, title = {The reestablishment of microbial communities after surface cleaning in schools.}, journal = {Journal of applied microbiology}, volume = {125}, number = {3}, pages = {897-906}, doi = {10.1111/jam.13898}, pmid = {29719941}, issn = {1365-2672}, abstract = {AIMS: The goal of this study was to quantify the indoor microbiome dynamics of bacterial and fungal communities on school desk surfaces during a cleaning intervention.

METHODS AND RESULTS: Quantitative PCR and DNA sequenced-based approaches were employed to describe microbial community dynamics on ten desk surfaces, spread across three schools, located in the Northeast region of the United States. Six samples were taken from each desk, one precleaning, and five postcleaning at 30 min, 1, 3, 7 and 21 days. Cleaning of the desks physically removed c. 50% of bacteria, fungi, and human cells and a full recovery of the surface microbial concentrations occurred within 2-5 days. This recovery period is much shorter than the schools' once per semester cleaning schedule. The dominant source of bacteria and fungi on desks at all time points came from the human microbiome (skin, oral cavity, and gut). More than 50% fungi on desks were members of genera that contain known allergens.

CONCLUSIONS: Microbial communities on these school desks are primarily generated and maintained from the deposition of human-associated bacteria and fungi. Current school surface cleaning protocols and cycles may be ineffective at reducing student exposure to fungal allergens and microbes of human origin.

Multiple students often share desks in schools. Results on the removal and reestablishment of microbial communities on these surfaces are critical for setting cleaning schedules and practices that effectively interrupt exposure to surface-associated pathogens and allergens.}, } @article {pmid29718276, year = {2018}, author = {Reen, FJ and McGlacken, GP and O'Gara, F}, title = {The expanding horizon of alkyl quinolone signalling and communication in polycellular interactomes.}, journal = {FEMS microbiology letters}, volume = {365}, number = {9}, pages = {}, doi = {10.1093/femsle/fny076}, pmid = {29718276}, issn = {1574-6968}, abstract = {Population dynamics within natural ecosystems is underpinned by microbial diversity and the heterogeneity of host-microbe and microbe-microbe interactions. Small molecule signals that intersperse between species have been shown to govern many virulence-related processes in established and emerging pathogens. Understanding the capacity of microbes to decode diverse languages and adapt to the presence of 'non-self' cells will provide an important new direction to the understanding of the 'polycellular' interactome. Alkyl quinolones (AQs) have been described in the ESKAPE pathogen Pseudomonas aeruginosa, the primary agent associated with mortality in patients with cystic fibrosis and the third most prevalent nosocomial pathogen worldwide. The role of these molecules in governing the physiology and virulence of P. aeruginosa and other pathogens has received considerable attention, while a role in interspecies and interkingdom communication has recently emerged. Herein we discuss recent advances in our understanding of AQ signalling and communication in the context of microbe-microbe and microbe-host interactions. The integrated knowledge from these systems-based investigations will facilitate the development of new therapeutics based on the AQ framework that serves to disarm the pathogenesis of P. aeruginosa and competing pathogens.}, } @article {pmid29715493, year = {2018}, author = {Rosado, MM and Aranburu, A and Scarsella, M and Cascioli, S and Giorda, E and Del Chierico, F and Mortera, SL and Mortari, EP and Petrini, S and Putignani, L and Carsetti, R}, title = {Spleen development is modulated by neonatal gut microbiota.}, journal = {Immunology letters}, volume = {199}, number = {}, pages = {1-15}, doi = {10.1016/j.imlet.2018.04.010}, pmid = {29715493}, issn = {1879-0542}, abstract = {The full development of the mammalian immune system occurs after birth upon exposure to non self-antigens. The gut is the first site of bacterial colonization where it is crucial to create the appropriate microenvironment able to balance effector or tolerogenic responses to external stimuli. It is a well-established fact that at mucosal sites bacteria play a key role in developing the immune system but we ignore how colonising bacteria impact the maturation of the spleen. Here we addressed this issue. Taking advantage of the fact that milk SIgA regulates bacterial colonization of the newborn intestine, we generated immunocompetent mice born either from IgA pro-efficient or IgA deficient females. Having demonstrated that SIgA in maternal milk modulates neonatal gut microbiota by promoting an increased diversity of the colonizing species we also found that immunocompetent pups, not exposed to milk SIgA, fail to properly develop the FDC network and primary follicles in the spleen compromising the response to T-dependent antigens. The presence of a less diverse microbiota with a higher representation of pathogenic species leads to a fast replenishment of the marginal zone and the IgM plasma cell compartment of the spleen as well as IgA plasma cells in the gut.}, } @article {pmid29710488, year = {2018}, author = {Zhang, Y and Wang, X and Li, H and Ni, C and Du, Z and Yan, F}, title = {Human oral microbiota and its modulation for oral health.}, journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie}, volume = {99}, number = {}, pages = {883-893}, doi = {10.1016/j.biopha.2018.01.146}, pmid = {29710488}, issn = {1950-6007}, mesh = {Dental Caries/microbiology ; Humans ; *Microbiota ; Mouth/*microbiology ; Mouth Diseases/*microbiology ; Oral Health ; Periodontal Diseases/microbiology ; }, abstract = {The oral microbiome is an important part of the human microbiome. The oral cavity contains several significantly different niches with distinct microbial communities. A wide range of microorganisms inhabit the human oral cavity, including bacteria, fungi, viruses, archaea and protozoa. These microorganisms form a complex ecological community that influences oral and systemic health. The most prevalent oral diseases, dental caries and periodontal diseases, are microbiota-associated diseases. Moreover, increasing evidences have supported that many systemic diseases are associated with disturbances in the oral ecosystem, such as diabetes, cardiovascular diseases and tumors. The current control of dental plaque-related diseases is nonspecific and is centered on the removal of plaque by mechanical means. Due to this realization about the oral microbiome, several new methods based on the modulation of the microbiome that aim at maintaining and reestablishing a healthy oral ecosystem have been developed.}, } @article {pmid29704918, year = {2018}, author = {Wilkinson, EM and Ilhan, ZE and Herbst-Kralovetz, MM}, title = {Microbiota-drug interactions: Impact on metabolism and efficacy of therapeutics.}, journal = {Maturitas}, volume = {112}, number = {}, pages = {53-63}, doi = {10.1016/j.maturitas.2018.03.012}, pmid = {29704918}, issn = {1873-4111}, mesh = {Animals ; Anti-Infective Agents/pharmacokinetics ; Anti-Inflammatory Agents/pharmacokinetics ; Antineoplastic Agents/pharmacokinetics ; Biotransformation ; *Drug Therapy ; Drug-Related Side Effects and Adverse Reactions/*metabolism ; Female ; Gastrointestinal Microbiome ; Humans ; Immunologic Factors/pharmacokinetics ; *Microbiota ; Vagina/microbiology ; }, abstract = {The microbiome not only represents a vital modifier of health and disease, but is a clinically important drug target. Therefore, study of the impact of the human microbiome on drug metabolism, toxicity and efficacy is urgently needed. This review focuses on gut and vaginal microbiomes, and the effect of those microbiomes or components thereof on the pharmacokinetics of specific chemotherapeutic agents, immunotherapies, anti-inflammatory and antimicrobial drugs. In some cases, the presence of specific bacterial species within the microbiome can alter the metabolism of certain drugs, such as chemotherapeutic agents and antiviral drugs. These microbiota-drug interactions are identified mostly through studies using germ-free or microbiome-depleted animal models, or by the administration of specific bacterial isolates. The biotransformation of drugs can cause drug-related toxicities; however, biotransformation also provides a mechanism by which drug developers could exploit host microbiota to create more site-specific drugs. Within this review we consider the importance of the route of drug administration and interactions with microbiota at various mucosal sites. Notably, we discuss the potential utility of bacterial therapeutics in altering the microbiome to enhance therapeutic efficacy and clinical outcomes in a personalized fashion. Based on the data to date, there is a clinically important relationship between microbiota and drug metabolism throughout the lifespan; therefore, profiling of the human microbiome will be essential in order to understand the mechanisms by which these microbiota-drug interactions occur and the degree to which this complex interplay affects drug efficacy.}, } @article {pmid29693574, year = {2018}, author = {Del Chierico, F and Cardile, S and Pietrobattista, A and Liccardo, D and Russo, A and Candusso, M and Basso, MS and Grimaldi, C and Pansani, L and Bernaschi, P and Torre, G and Putignani, L}, title = {Liver Transplantation and Gut Microbiota Profiling in a Child Colonized by a Multi-Drug Resistant Klebsiella pneumoniae: A New Approach to Move from Antibiotic to "Eubiotic" Control of Microbial Resistance.}, journal = {International journal of molecular sciences}, volume = {19}, number = {5}, pages = {}, doi = {10.3390/ijms19051280}, pmid = {29693574}, issn = {1422-0067}, mesh = {Anti-Bacterial Agents/pharmacology/therapeutic use ; Carbapenems/pharmacology/therapeutic use ; *Drug Resistance, Bacterial ; Female ; *Gastrointestinal Microbiome ; Humans ; Infant ; Klebsiella Infections/diagnosis/drug therapy/*microbiology ; Klebsiella pneumoniae/*drug effects/genetics/pathogenicity ; Liver Transplantation/*adverse effects ; Postoperative Complications/*diagnosis/drug therapy/*microbiology ; }, abstract = {The increase of microorganisms multi-drug resistant (MDR) to antibiotics (ATBs) is becoming a global emergency, especially in frail subjects. In chronic liver disease (LD) with indications for liver transplantation (LT), MDR colonization can significantly affect the LT outcome. However, no clear guidelines for microbial management are available. A novel approach toward MDR-colonized patients undergoing LT was developed at our Center refraining from ATBs use during the transplant waiting list, and use of an intensive perioperative prophylaxis cycle. This study aimed to couple clinical evaluation with monitoring of gut microbiota in a pediatric LD patient colonized with MDR Klebsiella pneumoniae (KP) who underwent LT. No peri-transplant complications were reported, and a decontamination from the MDR bacteria occurred during follow-up. Significant changes in gut microbiota, especially during ATB treatment, were reported by microbiota profiling. Patterns of Klebsiella predominance and microbiota diversity revealed opposite temporal trends, with Klebsiella ecological microbiota niches linked to ATB-driven selection. Our infection control program appeared to control complications following LT in an MDR-KP-colonized patient. The perioperative ATB regimen, acting as LT prophylaxis, triggered MDR-KP overgrowth and gut dysbiosis, but buffered infectious processes. Mechanisms modulating the gut ecosystem should be taken into account in MDR colonization clinical management.}, } @article {pmid29692798, year = {2018}, author = {Roche-Lima, A and Carrasquillo-Carrión, K and Gómez-Moreno, R and Cruz, JM and Velázquez-Morales, DM and Rogozin, IB and Baerga-Ortiz, A}, title = {The Presence of Genotoxic and/or Pro-inflammatory Bacterial Genes in Gut Metagenomic Databases and Their Possible Link With Inflammatory Bowel Diseases.}, journal = {Frontiers in genetics}, volume = {9}, number = {}, pages = {116}, doi = {10.3389/fgene.2018.00116}, pmid = {29692798}, issn = {1664-8021}, support = {U54 MD007600/MD/NIMHD NIH HHS/United States ; R25 GM061838/GM/NIGMS NIH HHS/United States ; G12 RR003051/RR/NCRR NIH HHS/United States ; G12 MD007600/MD/NIMHD NIH HHS/United States ; R21 CA198963/CA/NCI NIH HHS/United States ; }, abstract = {Background: The human gut microbiota is a dynamic community of microorganisms that mediate important biochemical processes. Differences in the gut microbial composition have been associated with inflammatory bowel diseases (IBD) and other intestinal disorders. In this study, we quantified and compared the frequencies of eight genotoxic and/or pro-inflammatory bacterial genes found in metagenomic Whole Genome Sequences (mWGSs) of samples from individuals with IBD vs. a cohort of healthy human subjects. Methods: The eight selected gene sequences were clbN, clbB, cif, cnf-1, usp, tcpC from Escherichia coli, gelE from Enterococcus faecalis and murB from Akkermansia muciniphila. We also included the sequences for the conserved murB genes from E. coli and E. faecalis as markers for the presence of Enterobacteriaceae or Enterococci in the samples. The gene sequences were chosen based on their previously reported ability to disrupt normal cellular processes to either promote inflammation or to cause DNA damage in cultured cells or animal models, which could be linked to a role in IBD. The selected sequences were searched in three different mWGS datasets accessed through the Human Microbiome Project (HMP): a healthy cohort (N = 251), a Crohn's disease cohort (N = 60) and an ulcerative colitis cohort (N = 17). Results: Firstly, the sequences for the murB housekeeping genes from Enterobacteriaceae and Enterococci were more frequently found in the IBD cohorts (32% E. coli in IBD vs. 12% in healthy; 13% E. faecalis in IBD vs. 3% in healthy) than in the healthy cohort, confirming earlier reports of a higher presence of both of these taxa in IBD. For some of the sequences in our study, especially usp and gelE, their frequency was even more sharply increased in the IBD cohorts than in the healthy cohort, suggesting an association with IBD that is not easily explained by the increased presence of E. coli or E. faecalis in those samples. Conclusion: Our results suggest a significant association between the presence of some of these genotoxic or pro-inflammatory gene sequences and IBDs. In addition, these results illustrate the power and limitations of the HMP database in the detection of possible clinical correlations for individual bacterial genes.}, } @article {pmid29686658, year = {2018}, author = {Quagliariello, A and Del Chierico, F and Russo, A and Reddel, S and Conte, G and Lopetuso, LR and Ianiro, G and Dallapiccola, B and Cardona, F and Gasbarrini, A and Putignani, L}, title = {Gut Microbiota Profiling and Gut-Brain Crosstalk in Children Affected by Pediatric Acute-Onset Neuropsychiatric Syndrome and Pediatric Autoimmune Neuropsychiatric Disorders Associated With Streptococcal Infections.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {675}, doi = {10.3389/fmicb.2018.00675}, pmid = {29686658}, issn = {1664-302X}, abstract = {Pediatric acute-onset neuropsychiatric syndrome (PANS) and pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections syndrome (PANDAS) are conditions that impair brain normal neurologic function, resulting in the sudden onset of tics, obsessive-compulsive disorder, and other behavioral symptoms. Recent studies have emphasized the crosstalk between gut and brain, highlighting how gut composition can influence behavior and brain functions. Thus, the present study investigates the relationship between PANS/PANDAS and gut microbiota ecology. The gut composition of a cohort of 30 patients with PANS/PANDAS was analyzed and compared to control subjects using 16S rRNA-based metagenomics. Data were analyzed for their α- and β-diversity; differences in bacterial distribution were detected by Wilcoxon and LEfSe tests, while metabolic profile was predicted via PICRUSt software. These analyses demonstrate the presence of an altered bacterial community structure in PANS/PANDAS patients with respect to controls. In particular, ecological analysis revealed the presence of two main clusters of subjects based on age range. Thus, to avoid age bias, data from patients and controls were split into two groups: 4-8 years old and >9 years old. The younger PANS/PANDAS group was characterized by a strong increase in Bacteroidetes; in particular, Bacteroides, Odoribacter, and Oscillospira were identified as potential microbial biomarkers of this composition type. Moreover, this group exhibited an increase of several pathways concerning the modulation of the antibody response to inflammation within the gut as well as a decrease in pathways involved in brain function (i.e., SCFA, D-alanine and tyrosine metabolism, and the dopamine pathway). The older group of patients displayed a less uniform bacterial profile, thus impairing the identification of distinct biomarkers. Finally, Pearson's analysis between bacteria and anti-streptolysin O titer reveled a negative correlation between genera belonging to Firmicutes phylum and anti-streptolysin O while a positive correlation was observed with Odoribacter. In conclusion, this study suggests that streptococcal infections alter gut bacterial communities leading to a pro-inflammatory status through the selection of specific bacterial strains associated with gut inflammation and immune response activation. These findings highlight the possibility of studying bacterial biomarkers associated with this disorder and might led to novel potential therapeutic strategies.}, } @article {pmid29685174, year = {2018}, author = {Fan, X and Peters, BA and Jacobs, EJ and Gapstur, SM and Purdue, MP and Freedman, ND and Alekseyenko, AV and Wu, J and Yang, L and Pei, Z and Hayes, RB and Ahn, J}, title = {Drinking alcohol is associated with variation in the human oral microbiome in a large study of American adults.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {59}, doi = {10.1186/s40168-018-0448-x}, pmid = {29685174}, issn = {2049-2618}, support = {R01 CA159036/CA/NCI NIH HHS/United States ; U01CA182370//National Cancer Institute/ ; R21CA183887//National Cancer Institute/ ; Pancreas Cancer Action Network Career Development Award//American Association for Cancer Research/ ; P30CA016087//National Cancer Institute/ ; R03CA159414//National Cancer Institute/ ; R01CA159036//National Cancer Institute/ ; R01CA164964//National Cancer Institute/ ; R01 CA164964/CA/NCI NIH HHS/United States ; }, abstract = {BACKGROUND: Dysbiosis of the oral microbiome can lead to local oral disease and potentially to cancers of the head, neck, and digestive tract. However, little is known regarding exogenous factors contributing to such microbial imbalance.

RESULTS: We examined the impact of alcohol consumption on the oral microbiome in a cross-sectional study of 1044 US adults. Bacterial 16S rRNA genes from oral wash samples were amplified, sequenced, and assigned to bacterial taxa. We tested the association of alcohol drinking level (non-drinker, moderate drinker, or heavy drinker) and type (liquor, beer, or wine) with overall microbial composition and individual taxon abundance. The diversity of oral microbiota and overall bacterial profiles differed between heavy drinkers and non-drinkers (α-diversity richness p = 0.0059 and β-diversity unweighted UniFrac p = 0.0036), and abundance of commensal order Lactobacillales tends to be decreased with higher alcohol consumption (fold changes = 0.89 and 0.94 for heavy and moderate drinkers, p trend = 0.005 [q = 0.064]). Additionally, certain genera were enriched in subjects with higher alcohol consumption, including Actinomyces, Leptotrichia, Cardiobacterium, and Neisseria; some of these genera contain oral pathogens, while Neisseria can synthesize the human carcinogen acetaldehyde from ethanol. Wine drinkers may differ from non-drinkers in microbial diversity and profiles (α-diversity richness p = 0.048 and β-diversity unweighted UniFrac p = 0.059) after controlling for drinking amount, while liquor and beer drinkers did not. All significant differences between drinkers and non-drinkers remained after exclusion of current smokers.

CONCLUSIONS: Our results, from a large human study of alcohol consumption and the oral microbiome, indicate that alcohol consumption, and heavy drinking in particular, may influence the oral microbiome composition. These findings may have implications for better understanding the potential role that oral bacteria play in alcohol-related diseases.}, } @article {pmid29682676, year = {2018}, author = {Cong, J and Zhang, X}, title = {How human microbiome talks to health and disease.}, journal = {European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology}, volume = {37}, number = {9}, pages = {1595-1601}, doi = {10.1007/s10096-018-3263-1}, pmid = {29682676}, issn = {1435-4373}, support = {2016M602094//China Postdoctoral Science Foundation/ ; 2016047//Qingdao Application Research Project/ ; 16-6-2-3-nsh//Qingdao People's Livelihood Science and Technology Program/ ; }, abstract = {Microbes are ubiquitous in the human body. They usually live in communities, and each of these communities has a distinct taxonomical structure. Due to its close relationship with human health and disease, the human microbiome has received great attention and is probably considered to be the most valuable biomarker in preventing and solving human diseases. In this paper, we first review the value of the human microbiome. Then, we focus on the role of the human microbiome in influencing human health and disease. Furthermore, we intensively discuss the relationship between intestinal microbiota and cancer therapy. Finally, we briefly summarize the significance of the human microbiome based on the development of sequencing and bioinformatic techniques.}, } @article {pmid29675808, year = {2018}, author = {Ma, Y and Chen, H and Lan, C and Ren, J}, title = {Help, hope and hype: ethical considerations of human microbiome research and applications.}, journal = {Protein & cell}, volume = {9}, number = {5}, pages = {404-415}, doi = {10.1007/s13238-018-0537-4}, pmid = {29675808}, issn = {1674-8018}, } @article {pmid29673211, year = {2018}, author = {Harsch, IA and Konturek, PC}, title = {The Role of Gut Microbiota in Obesity and Type 2 and Type 1 Diabetes Mellitus: New Insights into "Old" Diseases.}, journal = {Medical sciences (Basel, Switzerland)}, volume = {6}, number = {2}, pages = {}, doi = {10.3390/medsci6020032}, pmid = {29673211}, issn = {2076-3271}, abstract = {The investigation of the human microbiome is the most rapidly expanding field in biomedicine. Early studies were undertaken to better understand the role of microbiota in carbohydrate digestion and utilization. These processes include polysaccharide degradation, glycan transport, glycolysis, and short-chain fatty acid production. Recent research has demonstrated that the intricate axis between gut microbiota and the host metabolism is much more complex. Gut microbiota&mdash;depending on their composition&mdash;have disease-promoting effects but can also possess protective properties. This review focuses on disorders of metabolic syndrome, with special regard to obesity as a prequel to type 2 diabetes, type 2 diabetes itself, and type 1 diabetes. In all these conditions, differences in the composition of the gut microbiota in comparison to healthy people have been reported. Mechanisms of the interaction between microbiota and host that have been characterized thus far include an increase in energy harvest, modulation of free fatty acids&mdash;especially butyrate&mdash;of bile acids, lipopolysaccharides, gamma-aminobutyric acid (GABA), an impact on toll-like receptors, the endocannabinoid system and &ldquo;metabolic endotoxinemia&rdquo; as well as &ldquo;metabolic infection.&rdquo; This review will also address the influence of already established therapies for metabolic syndrome and diabetes on the microbiota and the present state of attempts to alter the gut microbiota as a therapeutic strategy.}, } @article {pmid29672703, year = {2018}, author = {Keshri, V and Panda, A and Levasseur, A and Rolain, JM and Pontarotti, P and Raoult, D}, title = {Phylogenomic Analysis of β-Lactamase in Archaea and Bacteria Enables the Identification of Putative New Members.}, journal = {Genome biology and evolution}, volume = {10}, number = {4}, pages = {1106-1114}, doi = {10.1093/gbe/evy028}, pmid = {29672703}, issn = {1759-6653}, mesh = {Anti-Bacterial Agents/adverse effects/therapeutic use ; Archaea/enzymology ; Bacteria/enzymology ; Carbapenems/*biosynthesis/chemistry ; Humans ; Metagenomics ; *Phylogeny ; beta-Lactamases/*genetics ; beta-Lactams/*metabolism ; }, abstract = {β-lactamases are enzymes which are commonly produced by bacteria and which degrade the β-lactam ring of β-lactam antibiotics, namely penicillins, cephalosporins, carbapenems, and monobactams, and inactivate these antibiotics. We performed a rational and comprehensive investigation of β-lactamases in different biological databases. In this study, we constructed hidden Markov model profiles as well as the ancestral sequence of four classes of β-lactamases (A, B, C, and D), which were used to identify potential β-lactamases from environmental metagenomic (1206), human microbiome metagenomic (6417), human microbiome reference genome (1310), and NCBI's nonredundant databases (44101). Our analysis revealed the existence of putative β-lactamases in the metagenomic databases, which appeared to be similar to the four different molecular classes (A-D). This is the first report on the large-scale phylogenetic diversity of new members of β-lactamases, and our results revealed that metagenomic database dark-matter contains β-lactamase-like antibiotic resistance genes.}, } @article {pmid29669589, year = {2018}, author = {Coelho, LP and Kultima, JR and Costea, PI and Fournier, C and Pan, Y and Czarnecki-Maulden, G and Hayward, MR and Forslund, SK and Schmidt, TSB and Descombes, P and Jackson, JR and Li, Q and Bork, P}, title = {Similarity of the dog and human gut microbiomes in gene content and response to diet.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {72}, doi = {10.1186/s40168-018-0450-3}, pmid = {29669589}, issn = {2049-2618}, support = {686070//Horizon 2020 Framework Programme (BE)/ ; }, abstract = {BACKGROUND: Gut microbes influence their hosts in many ways, in particular by modulating the impact of diet. These effects have been studied most extensively in humans and mice. In this work, we used whole genome metagenomics to investigate the relationship between the gut metagenomes of dogs, humans, mice, and pigs.

RESULTS: We present a dog gut microbiome gene catalog containing 1,247,405 genes (based on 129 metagenomes and a total of 1.9 terabasepairs of sequencing data). Based on this catalog and taxonomic abundance profiling, we show that the dog microbiome is closer to the human microbiome than the microbiome of either pigs or mice. To investigate this similarity in terms of response to dietary changes, we report on a randomized intervention with two diets (high-protein/low-carbohydrate vs. lower protein/higher carbohydrate). We show that diet has a large and reproducible effect on the dog microbiome, independent of breed or sex. Moreover, the responses were in agreement with those observed in previous human studies.

CONCLUSIONS: We conclude that findings in dogs may be predictive of human microbiome results. In particular, a novel finding is that overweight or obese dogs experience larger compositional shifts than lean dogs in response to a high-protein diet.}, } @article {pmid29668831, year = {2018}, author = {Maziarz, M and Pfeiffer, RM and Wan, Y and Gail, MH}, title = {Using standard microbiome reference groups to simplify beta-diversity analyses and facilitate independent validation.}, journal = {Bioinformatics (Oxford, England)}, volume = {34}, number = {19}, pages = {3249-3257}, doi = {10.1093/bioinformatics/bty297}, pmid = {29668831}, issn = {1367-4811}, abstract = {Motivation: Comparisons of microbiome communities across populations are often based on pairwise distance measures (beta-diversity). Standard analyses (principal coordinate plots, permutation tests, kernel methods) require access to primary data if another investigator wants to add or compare independent data. We propose using standard reference measurements to simplify microbiome beta-diversity analyses, to make them more transparent, and to facilitate independent validation and comparisons across studies.

Results: Using stool and nasal reference sets from the Human Microbiome Project (HMP), we computed mean distances (actually Bray-Curtis or Pearson correlation dissimilarities) to each reference set for each new sample. Thus, each new sample has two mean distances that can be plotted and analyzed with classical statistical methods. To test the approach, we studied independent (not reference) HMP subjects. Simple Hotelling tests demonstrated statistically significant differences in mean distances to reference sets between all pairs of body sites (stool, skin, nasal, saliva and vagina) at the phylum, class, order, family and genus levels. Using the distance to a single reference set was usually sufficient, but using both reference sets always worked well. The use of reference sets simplifies standard analyses of beta-diversity and facilitates the independent validation and combining of such data because others can compute distances to the same reference sets. Moreover, standard statistical methods for survival analysis, logistic regression and other procedures can be applied to vectors of mean distances to reference sets, thereby greatly expanding the potential uses of beta-diversity information. More work is needed to identify the best reference sets for particular applications.

https://github.com/NCI-biostats/microbiome-fixed-reference.

Supplementary information: Supplementary data are available at Bioinformatics online.}, } @article {pmid29668682, year = {2018}, author = {Hannigan, GD and Duhaime, MB and Koutra, D and Schloss, PD}, title = {Biogeography and environmental conditions shape bacteriophage-bacteria networks across the human microbiome.}, journal = {PLoS computational biology}, volume = {14}, number = {4}, pages = {e1006099}, doi = {10.1371/journal.pcbi.1006099}, pmid = {29668682}, issn = {1553-7358}, support = {T32AI007528/NH/NIH HHS/United States ; P30 DK034933/DK/NIDDK NIH HHS/United States ; P30DK034933/NH/NIH HHS/United States ; U01AI124255/NH/NIH HHS/United States ; U19AI09087/NH/NIH HHS/United States ; }, mesh = {Bacteria/*genetics ; *Bacterial Physiological Phenomena ; Bacteriophages/*genetics/*physiology ; Computational Biology ; Diet ; Humans ; Metagenomics ; Microbial Consortia/genetics/physiology ; Microbiota/*genetics/*physiology ; Models, Biological ; Phylogeography ; Skin/microbiology/virology ; }, abstract = {Viruses and bacteria are critical components of the human microbiome and play important roles in health and disease. Most previous work has relied on studying bacteria and viruses independently, thereby reducing them to two separate communities. Such approaches are unable to capture how these microbial communities interact, such as through processes that maintain community robustness or allow phage-host populations to co-evolve. We implemented a network-based analytical approach to describe phage-bacteria network diversity throughout the human body. We built these community networks using a machine learning algorithm to predict which phages could infect which bacteria in a given microbiome. Our algorithm was applied to paired viral and bacterial metagenomic sequence sets from three previously published human cohorts. We organized the predicted interactions into networks that allowed us to evaluate phage-bacteria connectedness across the human body. We observed evidence that gut and skin network structures were person-specific and not conserved among cohabitating family members. High-fat diets appeared to be associated with less connected networks. Network structure differed between skin sites, with those exposed to the external environment being less connected and likely more susceptible to network degradation by microbial extinction events. This study quantified and contrasted the diversity of virome-microbiome networks across the human body and illustrated how environmental factors may influence phage-bacteria interactive dynamics. This work provides a baseline for future studies to better understand system perturbations, such as disease states, through ecological networks.}, } @article {pmid29666626, year = {2018}, author = {Ichinohe, T and Miyama, T and Kawase, T and Honjo, Y and Kitaura, K and Sato, H and Shin-I, T and Suzuki, R}, title = {Next-Generation Immune Repertoire Sequencing as a Clue to Elucidate the Landscape of Immune Modulation by Host-Gut Microbiome Interactions.}, journal = {Frontiers in immunology}, volume = {9}, number = {}, pages = {668}, doi = {10.3389/fimmu.2018.00668}, pmid = {29666626}, issn = {1664-3224}, abstract = {The human immune system is a fine network consisted of the innumerable numbers of functional cells that balance the immunity and tolerance against various endogenous and environmental challenges. Although advances in modern immunology have revealed a role of many unique immune cell subsets, technologies that enable us to capture the whole landscape of immune responses against specific antigens have been not available to date. Acquired immunity against various microorganisms including host microbiome is principally founded on T cell and B cell populations, each of which expresses antigen-specific receptors that define a unique clonotype. Over the past several years, high-throughput next-generation sequencing has been developed as a powerful tool to profile T- and B-cell receptor repertoires in a given individual at the single-cell level. Sophisticated immuno-bioinformatic analyses by use of this innovative methodology have been already implemented in clinical development of antibody engineering, vaccine design, and cellular immunotherapy. In this article, we aim to discuss the possible application of high-throughput immune receptor sequencing in the field of nutritional and intestinal immunology. Although there are still unsolved caveats, this emerging technology combined with single-cell transcriptomics/proteomics provides a critical tool to unveil the previously unrecognized principle of host-microbiome immune homeostasis. Accumulation of such knowledge will lead to the development of effective ways for personalized immune modulation through deeper understanding of the mechanisms by which the intestinal environment affects our immune ecosystem.}, } @article {pmid29665135, year = {2018}, author = {Ponziani, FR and Bhoori, S and Castelli, C and Putignani, L and Rivoltini, L and Del Chierico, F and Sanguinetti, M and Morelli, D and Paroni Sterbini, F and Petito, V and Reddel, S and Calvani, R and Camisaschi, C and Picca, A and Tuccitto, A and Gasbarrini, A and Pompili, M and Mazzaferro, V}, title = {Hepatocellular carcinoma is associated with gut microbiota profile and inflammation in nonalcoholic fatty liver disease.}, journal = {Hepatology (Baltimore, Md.)}, volume = {}, number = {}, pages = {}, doi = {10.1002/hep.30036}, pmid = {29665135}, issn = {1527-3350}, abstract = {The gut-liver axis plays a pivotal role in the pathogenesis of nonalcoholic fatty liver disease (NAFLD), which is the third leading cause of hepatocellular carcinoma (HCC) worldwide. However, the link between gut microbiota and hepatocarcinogenesis remains to be clarified. The aim of this study was to explore what features of the gut microbiota are associated with HCC in patients with cirrhosis and NAFLD. A consecutive series of patients with NAFLD-related cirrhosis and HCC (group 1, 21 patients), NAFLD-related cirrhosis without HCC (group 2, 20 patients), and healthy controls (group 3, 20 patients) was studied for gut microbiota profile, intestinal permeability, inflammatory status, and circulating mononuclear cells. We finally constructed a model depicting the most relevant correlations among these features, possibly involved in hepatocarcinogenesis. Patients with HCC showed increased levels of fecal calprotectin, while intestinal permeability was similar to patients with cirrhosis but without HCC. Plasma levels of interleukin 8 (IL8), IL13, chemokine (C-C motif) ligand (CCL) 3, CCL4, and CCL5 were higher in the HCC group and associated with an activated status of circulating monocytes. The fecal microbiota of the whole group of patients with cirrhosis showed higher abundance of Enterobacteriaceae and Streptococcus and a reduction in Akkermansia. Bacteroides and Ruminococcaceae were increased in the HCC group, while Bifidobacterium was reduced. Akkermansia and Bifidobacterium were inversely correlated with calprotectin concentration, which in turn was associated with humoral and cellular inflammatory markers. A similar behavior was also observed for Bacteroides.

CONCLUSION: Our results suggest that in patients with cirrhosis and NAFLD the gut microbiota profile and systemic inflammation are significantly correlated and can concur in the process of hepatocarcinogenesis. (Hepatology 2018).}, } @article {pmid29659479, year = {2018}, author = {Sudhakara, P and Gupta, A and Bhardwaj, A and Wilson, A}, title = {Oral Dysbiotic Communities and Their Implications in Systemic Diseases.}, journal = {Dentistry journal}, volume = {6}, number = {2}, pages = {}, doi = {10.3390/dj6020010}, pmid = {29659479}, issn = {2304-6767}, support = {R03 DE026526/DE/NIDCR NIH HHS/United States ; }, abstract = {The human body supports the growth of a wide array of microbial communities in various niches such as the oral cavity, gastro-intestinal and urogenital tracts, and on the surface of the skin. These host associated microbial communities include yet-un-cultivable bacteria and are influenced by various factors. Together, these communities of bacteria are referred to as the human microbiome. Human oral microbiome consists of both symbionts and pathobionts. Deviation from symbiosis among the bacterial community leads to &ldquo;dysbiosis&rdquo;, a state of community disturbance. Dysbiosis occurs due to many confounding factors that predispose a shift in the composition and relative abundance of microbial communities. Dysbiotic communities have been a major cause for many microbiome related systemic infections. Such dysbiosis is directed by certain important pathogens called the &ldquo;keystone pathogens&rdquo;, which can modulate community microbiome variations. One such persistent infection is oral infection, mainly periodontitis, where a wide array of causal organisms have been implied to systemic infections such as cardio vascular disease, diabetes mellitus, rheumatoid arthritis, and Alzheimer&rsquo;s disease. The keystone pathogens co-occur with many yet-cultivable bacteria and their interactions lead to dysbiosis. This has been the focus of recent research. While immune evasion is one of the major modes that leads to dysbiosis, new processes and new virulence factors of bacteria have been shown to be involved in this important process that determines a disease or health state. This review focuses on such dysbiotic communities, their interactions, and their virulence factors that predispose the host to other systemic implications.}, } @article {pmid29658784, year = {2018}, author = {Popic, V and Kuleshov, V and Snyder, M and Batzoglou, S}, title = {Fast Metagenomic Binning via Hashing and Bayesian Clustering.}, journal = {Journal of computational biology : a journal of computational molecular cell biology}, volume = {25}, number = {7}, pages = {677-688}, doi = {10.1089/cmb.2017.0250}, pmid = {29658784}, issn = {1557-8666}, abstract = {We introduce GATTACA, a framework for fast unsupervised binning of metagenomic contigs. Similar to recent approaches, GATTACA clusters contigs based on their coverage profiles across a large cohort of metagenomic samples; however, unlike previous methods that rely on read mapping, GATTACA quickly estimates these profiles from kmer counts stored in a compact index. This approach can result in over an order of magnitude speedup, while matching the accuracy of earlier methods on synthetic and real data benchmarks. It also provides a way to index metagenomic samples (e.g., from public repositories such as the Human Microbiome Project) offline once and reuse them across experiments; furthermore, the small size of the sample indices allows them to be easily transferred and stored. Leveraging the MinHash technique, GATTACA also provides an efficient way to identify publicly available metagenomic data that can be incorporated into the set of reference metagenomes to further improve binning accuracy. Thus, enabling easy indexing and reuse of publicly available metagenomic data sets, GATTACA makes accurate metagenomic analyses accessible to a much wider range of researchers.}, } @article {pmid29657964, year = {2018}, author = {Whiteson, KL}, title = {Vive la Persistence: Engineering Human Microbiomes in the 21st Century.}, journal = {mSystems}, volume = {3}, number = {2}, pages = {}, doi = {10.1128/mSystems.00166-17}, pmid = {29657964}, issn = {2379-5077}, abstract = {I imagine a future in which children grow up with healthy microbial communities. Engineering human microbiomes might actually be achievable in the near future, as we enter an era of hunting for human-adapted bacterial strains and phages. Furthermore, breath metabolites could allow us to track whether a probiotic colonizes persistently or a phage has knocked down a microbe of interest. Recent successes with probiotics, such as bifidobacteria that can break down human milk oligosaccharides, are making a future in which infants are intentionally colonized with health-promoting strains seem less unlikely. Viruses that infect bacteria, bacteriophages, are also important for human health both because of their role in the human microbiome and because of their potential for use in phage therapy. Monitoring the outcome of microbiome-focused interventions with breath volatile sampling is also on the horizon, which could mean real-time tracking of microbial metabolite production. Studies of early life during microbiome assembly, when the potential for effective interventions to reduce disease risk is greatest, are essential.}, } @article {pmid29654837, year = {2018}, author = {Seekatz, AM and Theriot, CM and Rao, K and Chang, YM and Freeman, AE and Kao, JY and Young, VB}, title = {Restoration of short chain fatty acid and bile acid metabolism following fecal microbiota transplantation in patients with recurrent Clostridium difficile infection.}, journal = {Anaerobe}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.anaerobe.2018.04.001}, pmid = {29654837}, issn = {1095-8274}, support = {K01 GM109236/GM/NIGMS NIH HHS/United States ; R35 GM119438/GM/NIGMS NIH HHS/United States ; U01 AI124255/AI/NIAID NIH HHS/United States ; U19 AI090871/AI/NIAID NIH HHS/United States ; }, abstract = {A significant proportion of individuals develop recurrent Clostridium difficile infection (CDI) following initial disease. Fecal microbiota transplantation (FMT), a highly effective treatment method for recurrent CDI, has been demonstrated to induce microbiota recovery. One of the proposed functions associated with restoration of colonization resistance against C. difficile has been recovery of bile acid metabolism. In this study, we aimed to assess recovery of short chain fatty acids (SCFAs) in addition to bile acids alongside microbial community structure in six patients with recurrent CDI following treatment with FMT over time. Using 16S rRNA gene-based sequencing, we observed marked similarity of the microbiota between recipients following FMT (n = 6, sampling up to 6 months post-FMT) and their respective donors. Sustained increases in the levels of the SCFAs butyrate, acetate, and propionate were observed post-FMT, and variable recovery over time was observed in the secondary bile acids deoxycholate and lithocholate. To correlate these changes with specific microbial taxa at an individual level, we applied a generalized estimating equation approach to model metabolite concentrations with the presence of specific members of the microbiota. Metabolites that increased following FMT were associated with bacteria classified within the Lachnospiraceae, Ruminococcaceae, and unclassified Clostridiales families. In contrast, members of these taxa were inversely associated with primary bile acids. The longitudinal aspect of this study allowed us to characterize individualized patterns of recovery, revealing variability between and within patients following FMT.}, } @article {pmid29643839, year = {2018}, author = {Zhai, J and Kim, J and Knox, KS and Twigg, HL and Zhou, H and Zhou, JJ}, title = {Variance Component Selection With Applications to Microbiome Taxonomic Data.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {509}, doi = {10.3389/fmicb.2018.00509}, pmid = {29643839}, issn = {1664-302X}, abstract = {High-throughput sequencing technology has enabled population-based studies of the role of the human microbiome in disease etiology and exposure response. Microbiome data are summarized as counts or composition of the bacterial taxa at different taxonomic levels. An important problem is to identify the bacterial taxa that are associated with a response. One method is to test the association of specific taxon with phenotypes in a linear mixed effect model, which incorporates phylogenetic information among bacterial communities. Another type of approaches consider all taxa in a joint model and achieves selection via penalization method, which ignores phylogenetic information. In this paper, we consider regression analysis by treating bacterial taxa at different level as multiple random effects. For each taxon, a kernel matrix is calculated based on distance measures in the phylogenetic tree and acts as one variance component in the joint model. Then taxonomic selection is achieved by the lasso (least absolute shrinkage and selection operator) penalty on variance components. Our method integrates biological information into the variable selection problem and greatly improves selection accuracies. Simulation studies demonstrate the superiority of our methods versus existing methods, for example, group-lasso. Finally, we apply our method to a longitudinal microbiome study of Human Immunodeficiency Virus (HIV) infected patients. We implement our method using the high performance computing language Julia. Software and detailed documentation are freely available at https://github.com/JingZhai63/VCselection.}, } @article {pmid29641531, year = {2018}, author = {Fan, X and Peters, BA and Min, D and Ahn, J and Hayes, RB}, title = {Comparison of the oral microbiome in mouthwash and whole saliva samples.}, journal = {PloS one}, volume = {13}, number = {4}, pages = {e0194729}, doi = {10.1371/journal.pone.0194729}, pmid = {29641531}, issn = {1932-6203}, support = {R01 CA159036/CA/NCI NIH HHS/United States ; R01 CA164964/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Bacteria/*classification ; Cohort Studies ; DNA, Bacterial/analysis ; Healthy Volunteers ; Humans ; Microbiota/*genetics ; Middle Aged ; Mouth Mucosa/microbiology ; *Mouthwashes ; Phylogeny ; Prospective Studies ; RNA, Ribosomal, 16S/genetics ; Saliva/*microbiology ; Specimen Handling ; }, abstract = {Population-based epidemiologic studies can provide important insight regarding the role of the microbiome in human health and disease. Buccal cells samples using commercial mouthwash have been obtained in large prospective cohorts for the purpose of studying human genomic DNA. We aimed to better understand if these mouthwash samples are also a valid resource for the study of the oral microbiome. We collected one saliva sample and one Scope mouthwash sample from 10 healthy subjects. Bacterial 16S rRNA genes from both types of samples were amplified, sequenced, and assigned to bacterial taxa. We comprehensively compared these paired samples for bacterial community composition and individual taxonomic abundance. We found that mouthwash samples yielded similar amount of bacterial DNA as saliva samples (p from Student's t-test for paired samples = 0.92). Additionally, the paired samples had similar within sample diversity (p from = 0.33 for richness, and p = 0.51 for Shannon index), and clustered as pairs for diversity when analyzed by unsupervised hierarchical cluster analysis. No significant difference was found in the paired samples with respect to the taxonomic abundance of major bacterial phyla, Bacteroidetes, Firmicutes, Proteobacteria, Fusobacteria, and Actinobacteria (FDR adjusted q values from Wilcoxin signed-rank test = 0.15, 0.15, 0.87, 1.00 and 0.15, respectively), and all identified genera, including genus Streptococcus (q = 0.21), Prevotella (q = 0.25), Neisseria (q = 0.37), Veillonella (q = 0.73), Fusobacterium (q = 0.19), and Porphyromonas (q = 0.60). These results show that mouthwash samples perform similarly to saliva samples for analysis of the oral microbiome. Mouthwash samples collected originally for analysis of human DNA are also a resource suitable for human microbiome research.}, } @article {pmid29641525, year = {2018}, author = {Weber, KS and Bridgewater, LC and Jensen, JL and Breakwell, DP and Nielsen, BL and Johnson, SM}, title = {Personal microbiome analysis improves student engagement and interest in Immunology, Molecular Biology, and Genomics undergraduate courses.}, journal = {PloS one}, volume = {13}, number = {4}, pages = {e0193696}, doi = {10.1371/journal.pone.0193696}, pmid = {29641525}, issn = {1932-6203}, mesh = {Allergy and Immunology/*education ; *Attitude ; Genomics/*education ; Humans ; *Microbiota ; Molecular Biology/*education ; *Students ; Universities ; }, abstract = {A critical area of emphasis for science educators is the identification of effective means of teaching and engaging undergraduate students. Personal microbiome analysis is a means of identifying the microbial communities found on or in our body. We hypothesized the use of personal microbiome analysis in the classroom could improve science education by making courses more applied and engaging for undergraduate students. We determined to test this prediction in three Brigham Young University undergraduate courses: Immunology, Advanced Molecular Biology Laboratory, and Genomics. These three courses have a two-week microbiome unit and students during the 2016 semester students could submit their own personal microbiome kit or use the demo data, whereas during the 2017 semester students were given access to microbiome data from an anonymous individual. The students were surveyed before, during, and after the human microbiome unit to determine whether analyzing their own personal microbiome data, compared to analyzing demo microbiome data, impacted student engagement and interest. We found that personal microbiome analysis significantly enhanced the engagement and interest of students while completing microbiome assignments, the self-reported time students spent researching the microbiome during the two week microbiome unit, and the attitudes of students regarding the course overall. Thus, we found that integrating personal microbiome analysis in the classroom was a powerful means of improving student engagement and interest in undergraduate science courses.}, } @article {pmid29636512, year = {2018}, author = {Pechal, JL and Schmidt, CJ and Jordan, HR and Benbow, ME}, title = {A large-scale survey of the postmortem human microbiome, and its potential to provide insight into the living health condition.}, journal = {Scientific reports}, volume = {8}, number = {1}, pages = {5724}, doi = {10.1038/s41598-018-23989-w}, pmid = {29636512}, issn = {2045-2322}, abstract = {The microbiome plays many roles in human health, often through the exclusive lens of clinical interest. The inevitable end point for all living hosts, death, has its own altered microbiome configurations. However, little is understood about the ecology and changes of microbial communities after death, or their potential utility for understanding the health condition of the recently living. Here we reveal distinct postmortem microbiomes of human hosts from a large-scale survey of death cases representing a predominantly urban population, and demonstrated these microbiomes reflected antemortem health conditions within 24-48 hours of death. Our results characterized microbial community structure and predicted function from 188 cases representing a cross-section of an industrial-urban population. We found strong niche differentiation of anatomic habitat and microbial community turnover based on topographical distribution. Microbial community stability was documented up to two days after death. Additionally, we observed a positive relationship between cell motility and time since host death. Interestingly, we discovered evidence that microbial biodiversity is a predictor of antemortem host health condition (e.g., heart disease). These findings improve the understanding of postmortem host microbiota dynamics, and provide a robust dataset to test the postmortem microbiome as a tool for assessing health conditions in living populations.}, } @article {pmid29636439, year = {2018}, author = {Brown, CT and Xiong, W and Olm, MR and Thomas, BC and Baker, R and Firek, B and Morowitz, MJ and Hettich, RL and Banfield, JF}, title = {Hospitalized Premature Infants Are Colonized by Related Bacterial Strains with Distinct Proteomic Profiles.}, journal = {mBio}, volume = {9}, number = {2}, pages = {}, doi = {10.1128/mBio.00441-18}, pmid = {29636439}, issn = {2150-7511}, support = {R01 AI092531/AI/NIAID NIH HHS/United States ; R01 GM103600/GM/NIGMS NIH HHS/United States ; }, abstract = {During the first weeks of life, microbial colonization of the gut impacts human immune system maturation and other developmental processes. In premature infants, aberrant colonization has been implicated in the onset of necrotizing enterocolitis (NEC), a life-threatening intestinal disease. To study the premature infant gut colonization process, genome-resolved metagenomics was conducted on 343 fecal samples collected during the first 3 months of life from 35 premature infants housed in a neonatal intensive care unit, 14 of whom developed NEC, and metaproteomic measurements were made on 87 samples. Microbial community composition and proteomic profiles remained relatively stable on the time scale of a week, but the proteome was more variable. Although genetically similar organisms colonized many infants, most infants were colonized by distinct strains with metabolic profiles that could be distinguished using metaproteomics. Microbiome composition correlated with infant, antibiotics administration, and NEC diagnosis. Communities were found to cluster into seven primary types, and community type switched within infants, sometimes multiple times. Interestingly, some communities sampled from the same infant at subsequent time points clustered with those of other infants. In some cases, switches preceded onset of NEC; however, no species or community type could account for NEC across the majority of infants. In addition to a correlation of protein abundances with organism replication rates, we found that organism proteomes correlated with overall community composition. Thus, this genome-resolved proteomics study demonstrated that the contributions of individual organisms to microbiome development depend on microbial community context.IMPORTANCE Humans are colonized by microbes at birth, a process that is important to health and development. However, much remains to be known about the fine-scale microbial dynamics that occur during the colonization period. We conducted a genome-resolved study of microbial community composition, replication rates, and proteomes during the first 3 months of life of both healthy and sick premature infants. Infants were found to be colonized by similar microbes, but each underwent a distinct colonization trajectory. Interestingly, related microbes colonizing different infants were found to have distinct proteomes, indicating that microbiome function is not only driven by which organisms are present, but also largely depends on microbial responses to the unique set of physiological conditions in the infant gut.}, } @article {pmid29634682, year = {2018}, author = {Gilbert, JA and Blaser, MJ and Caporaso, JG and Jansson, JK and Lynch, SV and Knight, R}, title = {Current understanding of the human microbiome.}, journal = {Nature medicine}, volume = {24}, number = {4}, pages = {392-400}, doi = {10.1038/nm.4517}, pmid = {29634682}, issn = {1546-170X}, abstract = {Our understanding of the link between the human microbiome and disease, including obesity, inflammatory bowel disease, arthritis and autism, is rapidly expanding. Improvements in the throughput and accuracy of DNA sequencing of the genomes of microbial communities that are associated with human samples, complemented by analysis of transcriptomes, proteomes, metabolomes and immunomes and by mechanistic experiments in model systems, have vastly improved our ability to understand the structure and function of the microbiome in both diseased and healthy states. However, many challenges remain. In this review, we focus on studies in humans to describe these challenges and propose strategies that leverage existing knowledge to move rapidly from correlation to causation and ultimately to translation into therapies.}, } @article {pmid29633119, year = {2018}, author = {Skowron, KB and Shogan, BD and Rubin, DT and Hyman, NH}, title = {The New Frontier: the Intestinal Microbiome and Surgery.}, journal = {Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract}, volume = {22}, number = {7}, pages = {1277-1285}, doi = {10.1007/s11605-018-3744-7}, pmid = {29633119}, issn = {1873-4626}, abstract = {The microbiome exerts a remarkable effect on human physiology. The study of the human-microbiome relationship is a burgeoning field with great potential to improve our understanding of health and disease. In this review, we address common surgical problems influenced by the human microbiome and explore what is thus far known about this relationship. These include inflammatory bowel disease, colorectal neoplasms, and diverticular disease. We will also discuss the effect of the microbiome on surgical complications, specifically anastomotic leak. We hope that further research in this field will enlighten our management of these and other surgical problems.}, } @article {pmid29629420, year = {2018}, author = {Langille, MGI}, title = {Exploring Linkages between Taxonomic and Functional Profiles of the Human Microbiome.}, journal = {mSystems}, volume = {3}, number = {2}, pages = {}, doi = {10.1128/mSystems.00163-17}, pmid = {29629420}, issn = {2379-5077}, abstract = {Microbiome studies typically focus on characterizing the taxonomic and functional profiles of the microbes within a community. Functional profiling is generally thought to be superior to taxonomic profiling for investigating human-microbe interactions, but there are several limitations and challenges to existing approaches. This Perspective discusses the current sequencing and bioinformatic methods for producing taxonomic and functional profiles, recent studies utilizing and comparing these technologies, and the existing challenges and limitations of these data. In addition, functional versus taxonomic conservation across the population is questioned, while future research that focuses on investigating the taxonomic diversity of microbial functions is proposed.}, } @article {pmid29629416, year = {2018}, author = {Lieberman, TD}, title = {Seven Billion Microcosms: Evolution within Human Microbiomes.}, journal = {mSystems}, volume = {3}, number = {2}, pages = {}, doi = {10.1128/mSystems.00171-17}, pmid = {29629416}, issn = {2379-5077}, abstract = {Rational microbiome-based therapies may one day treat a wide range of diseases and promote wellness. Yet, we are still limited in our abilities to employ such therapies and to predict which bacterial strains have the potential to stably colonize a person. The Lieberman laboratory is working to close this knowledge gap and to develop an understanding of how individual species and strains behave in the human microbiome, including with regard to their niche ranges, survival strategies, and the degree to which they adapt to individual people. We employ system-level approaches, with a particular emphasis on using de novo mutations and evolutionary inference to reconstruct the history of bacterial lineages within individuals.}, } @article {pmid29629415, year = {2018}, author = {David, LA}, title = {Toward Personalized Control of Human Gut Bacterial Communities.}, journal = {mSystems}, volume = {3}, number = {2}, pages = {}, doi = {10.1128/mSystems.00165-17}, pmid = {29629415}, issn = {2379-5077}, support = {R01 DK116187/DK/NIDDK NIH HHS/United States ; R24 DK110492/DK/NIDDK NIH HHS/United States ; }, abstract = {A key challenge in microbiology will be developing tools for manipulating human gut bacterial communities. Our ability to predict and control the dynamics of these communities is now in its infancy. To manage human gut microbiota, I am developing methods in three research domains. First, I am refining in vitro tools to experimentally study gut microbes at high throughput and in controlled settings. Second, I am adapting "big data" techniques to overcome statistical challenges confronting microbiota modeling. Third, I am testing study designs that can streamline human testing of microbiota manipulations. Assembling these methods creates new challenges, including training scientists who can work across disciplines such as engineering, ecology, and medicine. Nevertheless, I envision that overcoming these obstacles will enable my group to construct platforms that can personalize microbiota treatments, particularly ones based on diet. More broadly, I anticipate that such platforms will have applications across fields such as agriculture, biotechnology, and environmental management.}, } @article {pmid29627609, year = {2018}, author = {Lu, W and Negi, SS and Schein, CH and Maleki, SJ and Hurlburt, BK and Braun, W}, title = {Distinguishing allergens from non-allergenic homologues using Physical-Chemical Property (PCP) motifs.}, journal = {Molecular immunology}, volume = {99}, number = {}, pages = {1-8}, doi = {10.1016/j.molimm.2018.03.022}, pmid = {29627609}, issn = {1872-9142}, support = {R21 AI109090/AI/NIAID NIH HHS/United States ; }, abstract = {Quantitative guidelines to distinguish allergenic proteins from related, but non-allergenic ones are urgently needed for regulatory agencies, biotech companies and physicians. In a previous study, we found that allergenic proteins populate a relatively small number of protein families, as characterized by the Pfam database. However, these families also contain non-allergenic proteins, meaning that allergenic determinants must lie within more discrete regions of the sequence. Thus, new methods are needed to discriminate allergenic proteins within those families. Physical-Chemical Properties (PCP)-motifs specific for allergens within a Pfam class were determined for 17 highly populated protein domains. A novel scoring method based on PCP-motifs that characterize known allergenic proteins within these families was developed, and validated for those domains. The motif scores distinguished sequences of allergens from a large selection of 80,000 randomly selected non-allergenic sequences. The motif scores for the birch pollen allergen (Bet v 1) family, which also contains related fruit and nut allergens, correlated better than global sequence similarities with clinically observed cross-reactivities among those allergens. Further, we demonstrated that the average scores of allergen specific motifs for allergenic profilins are significantly different from the scores of non-allergenic profilins. Several of the selective motifs coincide with experimentally determined IgE epitopes of allergenic profilins. The motifs also discriminated allergenic pectate lyases, including Jun a 1 from mountain cedar pollen, from similar proteins in the human microbiome, which can be assumed to be non-allergens. The latter lacked key motifs characteristic of the known allergens, some of which correlate with known IgE binding sites.}, } @article {pmid29623445, year = {2018}, author = {Ho, HE and Bunyavanich, S}, title = {Role of the Microbiome in Food Allergy.}, journal = {Current allergy and asthma reports}, volume = {18}, number = {4}, pages = {27}, doi = {10.1007/s11882-018-0780-z}, pmid = {29623445}, issn = {1534-6315}, abstract = {PURPOSE OF REVIEW: Resident microbial communities likely modify risk for allergic disorders, including food allergy. We review epidemiologic studies linking microbial exposures to food allergy risk and discuss the mechanisms by which the microbiome may modulate oral tolerance. We additionally address ongoing translational efforts in human microbiome studies.

RECENT FINDINGS: Epidemiologic studies and murine models support that altered microbial exposures and colonization in early life modify food allergy risk. Differential microbiota confer protection or susceptibility to food allergy by modulating the regulatory tone of the mucosal immune system. Recent efforts are focused on the identification of bacterial strains necessary for oral tolerance in human and microbial-based clinical trials. Early childhood appears to be critical for the colonization of a diverse microbiota necessary for the induction and maintenance of oral tolerance. Identification and functional evaluation of protective commensal microbes will inform strategies for the prevention and treatment of food allergy.}, } @article {pmid29619642, year = {2018}, author = {Srinivasan, VB and Angrasan, M and Chandel, N and Rajamohan, G}, title = {Genome sequence and comparative analysis of Bacillus cereus BC04, reveals genetic diversity and alterations for antimicrobial resistance.}, journal = {Functional & integrative genomics}, volume = {18}, number = {4}, pages = {477-487}, doi = {10.1007/s10142-018-0600-5}, pmid = {29619642}, issn = {1438-7948}, support = {BT/HRD/NBA/34/01/2012//Department of Biotechnology , Ministry of Science and Technology/ ; BT/01/IYBA/2009//Department of Biotechnology , Ministry of Science and Technology/ ; BSC0119H//Council of Scientific and Industrial Research/ ; SB/YS/LS-177/2014//Science and Engineering Research Board/ ; }, mesh = {Bacillus cereus/classification/drug effects/*genetics ; Drug Resistance, Bacterial/*genetics ; *Genome, Bacterial ; Molecular Sequence Annotation ; Phylogeny ; *Polymorphism, Genetic ; }, abstract = {In this study, we delineated the genome sequence of a Bacillus cereus strain BC04 isolated from a stool sample in India. The draft genome is 5.1 Mb in size and consists of total 109 scaffolds, GC content is 35.2% with 5182 coding genes. The comparative analysis with other completely sequenced genomes highlights the unique presence of genomic islands, hemolysin, capsular synthetic protein, modifying enzymes accC7 and catA15, regulators of antibiotic resistance MarR and LysR with annotated functions related to virulence, stress response, and antimicrobial resistance. Overall, this study not only signifies the genetic diversity in gut isolate BC04 in particular, but also pinpoints the presence of unique genes possessed by B. cereus which can be pertinently exploited to design novel drugs and intervention strategies for the treatment of food borne diseases.}, } @article {pmid29617920, year = {2018}, author = {Demmer, RT}, title = {Invited Commentary: The Microbiome and Population Health-Considerations for Enhancing Study Design and Data Analysis in Observational and Interventional Epidemiology.}, journal = {American journal of epidemiology}, volume = {187}, number = {6}, pages = {1291-1294}, doi = {10.1093/aje/kwy063}, pmid = {29617920}, issn = {1476-6256}, support = {R01 DK102932/DK/NIDDK NIH HHS/United States ; }, abstract = {Measurement and characterization of the human microbiome in large population-based human studies has recently become a reality secondary to technological advances in high-throughput DNA sequencing. These advances bring new challenges and knowledge gaps for study planning, data analysis, and interpretation that are novel to large-scale epidemiologic studies. In this issue of the Journal, Sinha et al. (Am J Epidemiol. 2018;187(6):1282-1290) have provided data with which to inform statistical power and sample size requirements for microbiome studies in population-based settings. This work serves as a helpful starting point for study planning while also serving as a springboard for discussion regarding additional considerations for improving microbiome research. This commentary emphasizes the importance of selecting microbiome metrics appropriate for the biological hypothesis under investigation, as well as the need for new analytical tools that can better capitalize on the unique yet rich information contained in microbiome data sets.}, } @article {pmid29608646, year = {2018}, author = {Sinha, R and Goedert, JJ and Vogtmann, E and Hua, X and Porras, C and Hayes, R and Safaeian, M and Yu, G and Sampson, J and Ahn, J and Shi, J}, title = {Quantification of Human Microbiome Stability Over 6 Months: Implications for Epidemiologic Studies.}, journal = {American journal of epidemiology}, volume = {187}, number = {6}, pages = {1282-1290}, doi = {10.1093/aje/kwy064}, pmid = {29608646}, issn = {1476-6256}, support = {R03 CA159414/CA/NCI NIH HHS/United States ; }, abstract = {Temporal variation in microbiome measurements can reduce statistical power in research studies. Quantification of this variation is essential for designing studies of chronic disease. We analyzed 16S ribosomal RNA profiles in paired biological specimens separated by 6 months from 3 studies conducted during 1985-2013 (a National Cancer Institute colorectal cancer study, a Costa Rica study, and the Human Microbiome Project). We evaluated temporal stability by calculating intraclass correlation coefficients (ICCs). Sample sizes needed in order to detect microbiome differences between equal numbers of cases and controls for a nested case-control design were calculated on the basis of estimated ICCs. Across body sites, 12 phylum-level ICCs were greater than 0.5. Similarly, 11 alpha-diversity ICCs were greater than 0.5. Fecal beta-diversity estimates had ICCs over 0.5. For a single collection with most microbiome metrics, detecting an odds ratio of 2.0 would require 300-500 cases when matching 1 case to 1 control at P = 0.05. Use of 2 or 3 sequential specimens reduces the number of required subjects by 40%-50% for low-ICC metrics. Relative abundances of major phyla and alpha-diversity metrics have low temporal stability. Thus, detecting associations of moderate effect size with these metrics will require large sample sizes. Because beta diversity for feces is reasonably stable over time, smaller sample sizes can detect associations with community composition. Sequential prediagnostic specimens from thousands of prospectively ascertained cases are required to detect modest disease associations with particular microbiome metrics.}, } @article {pmid29596364, year = {2018}, author = {Vallone, C and Rigon, G and Gulia, C and Baffa, A and Votino, R and Morosetti, G and Zaami, S and Briganti, V and Catania, F and Gaffi, M and Nucciotti, R and Costantini, FM and Piergentili, R and Putignani, L and Signore, F}, title = {Non-Coding RNAs and Endometrial Cancer.}, journal = {Genes}, volume = {9}, number = {4}, pages = {}, doi = {10.3390/genes9040187}, pmid = {29596364}, issn = {2073-4425}, abstract = {Non-coding RNAs (ncRNAs) are involved in the regulation of cell metabolism and neoplastic transformation. Recent studies have tried to clarify the significance of these information carriers in the genesis and progression of various cancers and their use as biomarkers for the disease; possible targets for the inhibition of growth and invasion by the neoplastic cells have been suggested. The significance of ncRNAs in lung cancer, bladder cancer, kidney cancer, and melanoma has been amply investigated with important results. Recently, the role of long non-coding RNAs (lncRNAs) has also been included in cancer studies. Studies on the relation between endometrial cancer (EC) and ncRNAs, such as small ncRNAs or micro RNAs (miRNAs), transfer RNAs (tRNAs), ribosomal RNAs (rRNAs), antisense RNAs (asRNAs), small nuclear RNAs (snRNAs), Piwi-interacting RNAs (piRNAs), small nucleolar RNAs (snoRNAs), competing endogenous RNAs (ceRNAs), lncRNAs, and long intergenic ncRNAs (lincRNAs) have been published. The recent literature produced in the last three years was extracted from PubMed by two independent readers, which was then selected for the possible relation between ncRNAs, oncogenesis in general, and EC in particular.}, } @article {pmid29570689, year = {2018}, author = {Cinelli, G and Fabrizi, M and Ravà, L and Signore, F and Vernocchi, P and Semeraro, M and Vallone, C and Lanciotti, R and Ciofi Degli Atti, M and Manco, M}, title = {Association between Maternal and Foetal Erythrocyte Fatty Acid Profiles and Birth Weight.}, journal = {Nutrients}, volume = {10}, number = {4}, pages = {}, doi = {10.3390/nu10040402}, pmid = {29570689}, issn = {2072-6643}, mesh = {Adult ; *Birth Weight ; Erythrocytes/*metabolism ; Fatty Acids/adverse effects/*blood ; Fatty Acids, Omega-6/blood ; Female ; Fetal Blood/*metabolism ; Gestational Age ; Humans ; Infant, Newborn ; *Infant, Small for Gestational Age ; Maternal Nutritional Physiological Phenomena ; Nutritional Status ; Pregnancy ; Risk Factors ; }, abstract = {Regular foetal development is crucial for assuring good health status in the offspring. The quality and quantity of maternal dietary fatty acids (FAs) can affect growth. The study aimed to: (1) investigate the association of maternal/foetal lipid profiles with birth weight (BW); and (2) compare these profiles in small, appropriate, and large for gestational age (SGA, AGA, and LGA) infants. FAs were measured in erythrocyte membranes using gas chromatography analysis in 607 mother-infant pairs (316 males, 52.1%). In the quantile regression, a significant association between BW and levels of maternal linoleic acid (LA; C18:2, n-6; coefficient: 18.66; p = 0.010), arachidonic acid (AA; C20:4, n-6; coefficient: 11.35; p = 0.007), docosahexaenoic acid (DHA; C22:6, n-3; coefficient: 29.73; p = 0.007), polyunsaturated FAs (coefficient: 8.55; p = 0.001), foetal DHA (coefficient: -22.82; p = 0.037), and saturated FAs (coefficient: -65.41; p = 0.002) was found. Myristic (C14:0) and pentadecanoic acids (C15:0), both maternal (p = 0.000; p = 0.017) and foetal (p = 0.009; p = 0.002), and maternal erucic acid (C22:1, n-9; p = 0.026) were found at higher levels in SGA infants as compared to AGA ones. Conversely, maternal LA, AA, and omega 6 FAs levels were higher in AGA infants (p = 0.037; p = 0.003; p = 0.026, respectively). Maternal and foetal polyunsaturated and omega 6 FAs levels are positively related to BW, while a lipid profile rich in saturated FAs and erucic acid may influence the risk of SGA.}, } @article {pmid29568746, year = {2018}, author = {Wu, H and Cai, L and Li, D and Wang, X and Zhao, S and Zou, F and Zhou, K}, title = {Metagenomics Biomarkers Selected for Prediction of Three Different Diseases in Chinese Population.}, journal = {BioMed research international}, volume = {2018}, number = {}, pages = {2936257}, doi = {10.1155/2018/2936257}, pmid = {29568746}, issn = {2314-6141}, mesh = {Algorithms ; Arthritis, Rheumatoid/*microbiology ; Asian Continental Ancestry Group/*genetics ; Biomarkers/*metabolism ; Diabetes Mellitus, Type 2/*microbiology ; Dysbiosis/genetics ; Female ; Humans ; Liver Cirrhosis/*microbiology ; Male ; Metagenome/*genetics ; Metagenomics/methods ; Microbiota/*genetics ; Middle Aged ; ROC Curve ; }, abstract = {The dysbiosis of human microbiome has been proven to be associated with the development of many human diseases. Metagenome sequencing emerges as a powerful tool to investigate the effects of microbiome on diseases. Identification of human gut microbiome markers associated with abnormal phenotypes may facilitate feature selection for multiclass classification. Compared with binary classifiers, multiclass classification models deploy more complex discriminative patterns. Here, we developed a pipeline to address the challenging characterization of multilabel samples. In this study, a total of 300 biomarkers were selected from the microbiome of 806 Chinese individuals (383 controls, 170 with type 2 diabetes, 130 with rheumatoid arthritis, and 123 with liver cirrhosis), and then logistic regression prediction algorithm was applied to those markers as the model intrinsic features. The estimated model produced an F1 score of 0.9142, which was better than other popular classification methods, and an average receiver operating characteristic (ROC) of 0.9475 showed a significant correlation between these selected biomarkers from microbiome and corresponding phenotypes. The results from this study indicate that machine learning is a vital tool in data mining from microbiome in order to identify disease-related biomarkers, which may contribute to the application of microbiome-based precision medicine in the future.}, } @article {pmid29568289, year = {2018}, author = {Flores Saiffe Farías, A and Mendizabal, AP and Morales, JA}, title = {An Ontology Systems Approach on Human Brain Expression and Metaproteomics.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {406}, doi = {10.3389/fmicb.2018.00406}, pmid = {29568289}, issn = {1664-302X}, abstract = {Research in the last decade has shown growing evidence of the gut microbiota influence on brain physiology. While many mechanisms of this influence have been proposed in animal models, most studies in humans are the result of a pathology-dysbiosis association and very few have related the presence of certain taxa with brain substructures or molecular pathways. In this paper, we associated the functional ontologies in the differential expression of brain substructures from the Allen Brain Atlas database, with those of the metaproteome from the Human Microbiome Project. Our results showed several coherent clustered ontologies where many taxa could influence brain expression and physiology. A detailed analysis of psychobiotics showed specific slim ontologies functionally associated with substructures in the basal ganglia and cerebellar cortex. Some of the most relevant slim ontology groups are related to Ion transport, Membrane potential, Synapse, DNA and RNA metabolism, and Antigen processing, while the most relevant neuropathology found was Parkinson disease. In some of these cases, new hypothetical gut microbiota-brain interaction pathways are proposed.}, } @article {pmid29566913, year = {2017}, author = {Ferreira, AK and Mambelli, LI and Pillai, SY}, title = {Intervening in disease through genetically-modified bacteria.}, journal = {Best practice & research. Clinical gastroenterology}, volume = {31}, number = {6}, pages = {693-697}, doi = {10.1016/j.bpg.2017.09.017}, pmid = {29566913}, issn = {1532-1916}, mesh = {Bacteria/growth & development/*pathogenicity ; Disease/*etiology ; Humans ; }, abstract = {The comprehension of the molecular basis of different diseases is rapidly being dissected as a consequence of advancing technology. Consequently, proteins with potential therapeutic usefulness, including cytokines and signaling molecules have been identified in the last decades. However, their clinical use is hampered by disadvantageous functional and economic considerations. One of the most important of these considerations is targeted topical delivery and also the synthesis of such proteins, which for intravenous use requires rigorous purification whereas proteins often do not withstand digestive degradation and thus cannot be applied per os. Recently, the idea of using genetically modified bacteria has emerged as an attempt to evade these important barriers. Using such bacteria can deliver therapeutic proteins or other molecules at place of disease, especially when disease is at a mucosal surface. Further, whereas intravenously applied therapeutic proteins require expensive methodology in order to become endotoxin-free, this is not necessary for local application of therapeutic proteins in the intestine. In addition, once created further propagation of genetically modified bacteria is both cheap and requires relatively little in conditioning with respect to transport of the medication, making such organisms also suitable for combating disease in developing countries with poor infrastructure. Although first human trials with such bacteria were already performed more as a decade ago, the recent revolution in our understanding of the role of human gut microbiome in health and diseases has unleashed a revolution in this field resulting in a plethora of potential novel prophylactic and therapeutic intervention against disease onset and development employing such organisms. Today, the engineering of human microbiome for health benefits and related applications now chances many aspects of biology, nanotechnology and chemistry. Here, we review genetically modified bacteria methodology as possible carriers of drug delivering and provided the origin and inspirations for new drug delivery systems.}, } @article {pmid29566911, year = {2017}, author = {Konstantinov, SR}, title = {Diet, microbiome, and colorectal cancer.}, journal = {Best practice & research. Clinical gastroenterology}, volume = {31}, number = {6}, pages = {675-681}, doi = {10.1016/j.bpg.2017.09.007}, pmid = {29566911}, issn = {1532-1916}, mesh = {Colorectal Neoplasms/*immunology/pathology ; *Diet ; Humans ; Microbiota/*immunology ; }, abstract = {The scientific interests in the colorectal cancer (CRC) associated microbiome have increased significantly in the past decade. Mechanistically, several members of the human microbiome and products thereof have been implicated as inductors of the pathogenic inflammation related to CRC. Conversely, the activities of the human intestinal microbial community influenced by specific diet might confer a protective effect against the CRC risks and progression. As the microbiome is both a key contributor and one of the tools to prevent CRC, the current review gives a summary of the CRC-associated microbiome and the dietary strategies relevant to CRC. As more evidences become available, new microbiome-based treatments and specific diets may emerge to reduce the CRC risk and improve CRC patients' quality of life.}, } @article {pmid29557050, year = {2018}, author = {Ezcurra, M}, title = {Dissecting cause and effect in host-microbiome interactions using the combined worm-bug model system.}, journal = {Biogerontology}, volume = {}, number = {}, pages = {}, doi = {10.1007/s10522-018-9752-x}, pmid = {29557050}, issn = {1573-6768}, abstract = {High-throughput molecular studies are greatly advancing our knowledge of the human microbiome and its specific role in governing health and disease states. A myriad of ongoing studies aim at identifying links between microbial community disequilibria (dysbiosis) and human diseases. However, due to the inherent complexity and heterogeneity of the human microbiome we need robust experimental models that allow the systematic manipulation of variables to test the multitude of hypotheses arisen from large-scale 'meta-omic' projects. The nematode C. elegans combined with bacterial models offers an avenue to dissect cause and effect in host-microbiome interactions. This combined model allows the genetic manipulation of both host and microbial genetics and the use of a variety of tools, to identify pathways affecting host health. A number of recent high impact studies have used C. elegans to identify microbial pathways affecting ageing and longevity, demonstrating the power of the combined C. elegans-bacterial model. Here I will review the current state of the field, what we have learned from using C. elegans to study gut microbiome and host interactions, and the potential of using this model system in the future.}, } @article {pmid29556544, year = {2018}, author = {Turnbaugh, PJ}, title = {Making Millennial Medicine More Meta.}, journal = {mSystems}, volume = {3}, number = {2}, pages = {}, doi = {10.1128/mSystems.00154-17}, pmid = {29556544}, issn = {2379-5077}, support = {R01 HL122593/HL/NHLBI NIH HHS/United States ; }, abstract = {Although the importance of human genetic polymorphisms in therapeutic outcomes is well established, the role of specific genotypic or copy number variants in our "second genome" (the microbiome) has been largely overlooked. In this Perspective, I will discuss three major barriers to integrating metagenomics into pharmacology, highlighting ongoing research by us and others that has begun to shed light on the mechanisms that link the human microbiome to the efficacy and toxicity of small-molecule and biological therapies. The challenges for the next 5 years and beyond are many, requiring interdisciplinary scientific teams working at the interface of chemistry and biology, and a consideration of far more variables than traditionally included in pharmacological modeling. However, the potential benefits are immense. Continued progress could enable more precise tools for predicting patient responses and the development of a new generation of therapeutics based on, or targeted at, the human microbiome.}, } @article {pmid29556543, year = {2018}, author = {}, title = {Conflict of Interest Declarations by Contributing Editors of the Special Issue on Early-Career Systems Microbiology Scientists, Sponsored by Janssen Human Microbiome Institute (JHMI).}, journal = {mSystems}, volume = {3}, number = {2}, pages = {}, doi = {10.1128/mSystems.00010-18}, pmid = {29556543}, issn = {2379-5077}, } @article {pmid29556541, year = {2018}, author = {Waldron, L}, title = {Data and Statistical Methods To Analyze the Human Microbiome.}, journal = {mSystems}, volume = {3}, number = {2}, pages = {}, doi = {10.1128/mSystems.00194-17}, pmid = {29556541}, issn = {2379-5077}, support = {R21 AI121784/AI/NIAID NIH HHS/United States ; U24 CA180996/CA/NCI NIH HHS/United States ; }, abstract = {The Waldron lab for computational biostatistics bridges the areas of cancer genomics and microbiome studies for public health, developing methods to exploit publicly available data resources and to integrate -omics studies.}, } @article {pmid29556534, year = {2018}, author = {Segata, N}, title = {On the Road to Strain-Resolved Comparative Metagenomics.}, journal = {mSystems}, volume = {3}, number = {2}, pages = {}, doi = {10.1128/mSystems.00190-17}, pmid = {29556534}, issn = {2379-5077}, abstract = {Metagenomics has transformed microbiology, but its potential has not been fully expressed yet. From computational methods for digging deeper into metagenomes to study designs for addressing specific hypotheses, the Segata Lab is pursuing an integrative metagenomic approach to describe and model human-associated microbial communities as collections of strains. Linking strain variants to host phenotypes and performing cultivation-free population genomics require large cohorts and meta-analysis strategies to synthesize available cohorts but can revolutionize our understanding of the personalized host-microbiome interface which is at the base of human health.}, } @article {pmid29554085, year = {2018}, author = {Douglas, AE}, title = {Which experimental systems should we use for human microbiome science?.}, journal = {PLoS biology}, volume = {16}, number = {3}, pages = {e2005245}, doi = {10.1371/journal.pbio.2005245}, pmid = {29554085}, issn = {1545-7885}, support = {R01 GM095372/GM/NIGMS NIH HHS/United States ; }, abstract = {Microbiome science is revealing that the phenotype and health of animals, including humans, depend on the sustained function of their resident microorganisms. In this essay, I argue for thoughtful choice of model systems for human microbiome science. A greater variety of experimental systems, including wider use of invertebrate models, would benefit biomedical research, while systems ill-suited to experimental and genetic manipulation can be used to address very limited sets of scientific questions. Microbiome science benefits from the coordinated use of multiple systems, which is facilitated by networks of researchers with expertise in different experimental systems.}, } @article {pmid29553575, year = {2018}, author = {Seshadri, R and Leahy, SC and Attwood, GT and Teh, KH and Lambie, SC and Cookson, AL and Eloe-Fadrosh, EA and Pavlopoulos, GA and Hadjithomas, M and Varghese, NJ and Paez-Espino, D and , and Perry, R and Henderson, G and Creevey, CJ and Terrapon, N and Lapebie, P and Drula, E and Lombard, V and Rubin, E and Kyrpides, NC and Henrissat, B and Woyke, T and Ivanova, NN and Kelly, WJ}, title = {Cultivation and sequencing of rumen microbiome members from the Hungate1000 Collection.}, journal = {Nature biotechnology}, volume = {36}, number = {4}, pages = {359-367}, doi = {10.1038/nbt.4110}, pmid = {29553575}, issn = {1546-1696}, support = {322820//European Research Council/International ; }, abstract = {Productivity of ruminant livestock depends on the rumen microbiota, which ferment indigestible plant polysaccharides into nutrients used for growth. Understanding the functions carried out by the rumen microbiota is important for reducing greenhouse gas production by ruminants and for developing biofuels from lignocellulose. We present 410 cultured bacteria and archaea, together with their reference genomes, representing every cultivated rumen-associated archaeal and bacterial family. We evaluate polysaccharide degradation, short-chain fatty acid production and methanogenesis pathways, and assign specific taxa to functions. A total of 336 organisms were present in available rumen metagenomic data sets, and 134 were present in human gut microbiome data sets. Comparison with the human microbiome revealed rumen-specific enrichment for genes encoding de novo synthesis of vitamin B12, ongoing evolution by gene loss and potential vertical inheritance of the rumen microbiome based on underrepresentation of markers of environmental stress. We estimate that our Hungate genome resource represents ∼75% of the genus-level bacterial and archaeal taxa present in the rumen.}, } @article {pmid29545777, year = {2018}, author = {Bochtler, M and Mizgalska, D and Veillard, F and Nowak, ML and Houston, J and Veith, P and Reynolds, EC and Potempa, J}, title = {The Bacteroidetes Q-Rule: Pyroglutamate in Signal Peptidase I Substrates.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {230}, doi = {10.3389/fmicb.2018.00230}, pmid = {29545777}, issn = {1664-302X}, abstract = {Bacteroidetes feature prominently in the human microbiome, as major colonizers of the gut and clinically relevant pathogens elsewhere. Here, we reveal a new Bacteroidetes specific feature in the otherwise widely conserved Sec/SPI (Sec translocase/signal peptidase I) pathway. In Bacteroidetes, but not the entire FCB group or related phyla, signal peptide cleavage exposes N-terminal glutamine residues in most SPI substrates. Reanalysis of published mass spectrometry data for five Bacteroidetes species shows that the newly exposed glutamines are cyclized to pyroglutamate (also termed 5-oxoproline) residues. Using the dental pathogen Porphyromonas gingivalis as a model, we identify the PG2157 (also called PG_RS09565, Q7MT37) as the glutaminyl cyclase in this species, and map the catalytic activity to the periplasmic face of the inner membrane. Genetic manipulations that alter the glutamine residue immediately after the signal peptide in the pre-pro-forms of the gingipains affect the extracellular proteolytic activity of RgpA, but not RgpB and Kgp. Glutamine statistics, mass spectrometry data and the mutagenesis results show that the N-terminal glutamine residues or their pyroglutamate cyclization products do not act as generic sorting signals.}, } @article {pmid29535205, year = {2018}, author = {Jacobson, AN and Choudhury, BP and Fischbach, MA}, title = {The Biosynthesis of Lipooligosaccharide from Bacteroides thetaiotaomicron.}, journal = {mBio}, volume = {9}, number = {2}, pages = {}, doi = {10.1128/mBio.02289-17}, pmid = {29535205}, issn = {2150-7511}, support = {DP1 DK113598/DK/NIDDK NIH HHS/United States ; R01 DK110174/DK/NIDDK NIH HHS/United States ; T32 GM064337/GM/NIGMS NIH HHS/United States ; }, abstract = {Lipopolysaccharide (LPS), a cell-associated glycolipid that makes up the outer leaflet of the outer membrane of Gram-negative bacteria, is a canonical mediator of microbe-host interactions. The most prevalent Gram-negative gut bacterial taxon, Bacteroides, makes up around 50% of the cells in a typical Western gut; these cells harbor ~300 mg of LPS, making it one of the highest-abundance molecules in the intestine. As a starting point for understanding the biological function of Bacteroides LPS, we have identified genes in Bacteroides thetaiotaomicron VPI 5482 involved in the biosynthesis of its lipid A core and glycan, generated mutants that elaborate altered forms of LPS, and used matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry to interrogate the molecular features of these variants. We demonstrate, inter alia, that the glycan does not appear to have a repeating unit, and so this strain produces lipooligosaccharide (LOS) rather than LPS. This result contrasts with Bacteroides vulgatus ATCC 8482, which by SDS-PAGE analysis appears to produce LPS with a repeating unit. Additionally, our identification of the B. thetaiotaomicron LOS oligosaccharide gene cluster allowed us to identify similar clusters in other Bacteroides species. Our work lays the foundation for developing a structure-function relationship for Bacteroides LPS/LOS in the context of host colonization.IMPORTANCE Much is known about the bacterial species and genes that make up the human microbiome, but remarkably little is known about the molecular mechanisms through which the microbiota influences host biology. A well-known mechanism by which bacteria influence the host centers around lipopolysaccharide (LPS), a component of the Gram-negative bacterial outer membrane. Pathogen-derived LPS is a potent ligand for host receptor Toll-like receptor 4, which plays an important role in sensing bacteria as part of the innate immune response. Puzzlingly, the most common genus of human gut bacteria, Bacteroides, produces LPS but does not elicit a potent proinflammatory response. Previous work showing that Bacteroides LPS differs structurally from pathogen-derived LPS suggested the outlines of an explanation. Here, we take the next step, elucidating the biosynthetic pathway for Bacteroides LPS and generating mutants in the process that will be of great use in understanding how this molecule modulates the host immune response.}, } @article {pmid29535201, year = {2018}, author = {Cross, KL and Chirania, P and Xiong, W and Beall, CJ and Elkins, JG and Giannone, RJ and Griffen, AL and Guss, AM and Hettich, RL and Joshi, SS and Mokrzan, EM and Martin, RK and Zhulin, IB and Leys, EJ and Podar, M}, title = {Insights into the Evolution of Host Association through the Isolation and Characterization of a Novel Human Periodontal Pathobiont, Desulfobulbus oralis.}, journal = {mBio}, volume = {9}, number = {2}, pages = {}, doi = {10.1128/mBio.02061-17}, pmid = {29535201}, issn = {2150-7511}, support = {R01 DE024463/DE/NIDCR NIH HHS/United States ; }, abstract = {The human oral microbiota encompasses representatives of many bacterial lineages that have not yet been cultured. Here we describe the isolation and characterization of previously uncultured Desulfobulbus oralis, the first human-associated representative of its genus. As mammalian-associated microbes rarely have free-living close relatives, D. oralis provides opportunities to study how bacteria adapt and evolve within a host. This sulfate-reducing deltaproteobacterium has adapted to the human oral subgingival niche by curtailing its physiological repertoire, losing some biosynthetic abilities and metabolic independence, and by dramatically reducing environmental sensing and signaling capabilities. The genes that enable free-living Desulfobulbus to synthesize the potent neurotoxin methylmercury were also lost by D. oralis, a notably positive outcome of host association. However, horizontal gene acquisitions from other members of the microbiota provided novel mechanisms of interaction with the human host, including toxins like leukotoxin and hemolysins. Proteomic and transcriptomic analysis revealed that most of those factors are actively expressed, including in the subgingival environment, and some are secreted. Similar to other known oral pathobionts, D. oralis can trigger a proinflammatory response in oral epithelial cells, suggesting a direct role in the development of periodontal disease.IMPORTANCE Animal-associated microbiota likely assembled as a result of numerous independent colonization events by free-living microbes followed by coevolution with their host and other microbes. Through specific adaptation to various body sites and physiological niches, microbes have a wide range of contributions, from beneficial to disease causing. Desulfobulbus oralis provides insights into genomic and physiological transformations associated with transition from an open environment to a host-dependent lifestyle and the emergence of pathogenicity. Through a multifaceted mechanism triggering a proinflammatory response, D. oralis is a novel periodontal pathobiont. Even though culture-independent approaches can provide insights into the potential role of the human microbiome "dark matter," cultivation and experimental characterization remain important to studying the roles of individual organisms in health and disease.}, } @article {pmid29532031, year = {2018}, author = {Kim, HJ and Kim, H and Kim, JJ and Myeong, NR and Kim, T and Park, T and Kim, E and Choi, JY and Lee, J and An, S and Sul, WJ}, title = {Fragile skin microbiomes in megacities are assembled by a predominantly niche-based process.}, journal = {Science advances}, volume = {4}, number = {3}, pages = {e1701581}, doi = {10.1126/sciadv.1701581}, pmid = {29532031}, issn = {2375-2548}, abstract = {Given the higher incidence of skin diseases in more urbanized populations and its association with the skin microbiome, we questioned how the skin microbiome differed depending on the degree of urbanization. Skin microbiomes of 231 healthy subjects in five large cities in China varied mainly with environment and socioeconomic status of the cities in question. The differences among microbiomes could be explained by the predominantly niche-based assembly of microbial communities, which was supported by a dominance test, β-null deviation, and edge-length abundance distribution. Networks among microbes in larger cities were more fragile, which may contribute to the higher incidence of skin diseases in more urbanized environments. These results suggest that microbial ecological theory can provide a framework for understanding crucial health-associated features of the human microbiome.}, } @article {pmid29525681, year = {2018}, author = {Wang, X and Zhang, L and Wang, Y and Liu, X and Zhang, H and Liu, Y and Shen, N and Yang, J and Gai, Z}, title = {Gut microbiota dysbiosis is associated with Henoch-Schönlein Purpura in children.}, journal = {International immunopharmacology}, volume = {58}, number = {}, pages = {1-8}, doi = {10.1016/j.intimp.2018.03.003}, pmid = {29525681}, issn = {1878-1705}, abstract = {BACKGROUND: Alterations in the intestinal microbiota have been associated with the development of allergic diseases, such as asthma and food allergies. However, there is no report detailing the role of microbiota alterations in Henoch-Schönlein Purpura (HSP) development.

METHOD: A total of 85 children with HSP and 70 healthy children were recruited for this study. Intestinal microbiota composition was analyzed by 16S rRNA gene-based pyrosequencing. Fecal microbial diversity and composition were compared.

RESULT: We compared the gut microbiota of 155 subjects and found that children with HSP exhibited gut microbial dysbiosis. Lower microbial diversity and richness were found in HSP patients when compared to the control group. Based on an analysis of similarities, the composition of the microbiota in HSP patients was also different from that of the control group (r = 0.306, P = 0.001). The relative abundance of the bacterial genera Dialister (P < 0.0001), Roseburia (P < 0.0001), and Parasutterella (P < 0.0001) was significantly decreased in HSP children, while the relative abundance of Parabacteroides (P < 0.006) and Enterococcus (P < 0.0001) in these children was significantly increased. Based on Spearman correlation analysis, the LOS showed a significant negative (P < 0.05) correlation with the genera Paraprevotella and Roseburia. Meanwhile, IgA levels exhibited a significant negative (P < 0.01) correlation with the genus Bifidobacterium.

CONCLUSIONS: Our results indicate that HSP is associated with significant compositional and structural changes in the gut microbiota. These results enhance the potential for future microbial-based therapies to improve the clinical outcome of HSP in children.}, } @article {pmid29522743, year = {2018}, author = {Ferreiro, A and Crook, N and Gasparrini, AJ and Dantas, G}, title = {Multiscale Evolutionary Dynamics of Host-Associated Microbiomes.}, journal = {Cell}, volume = {172}, number = {6}, pages = {1216-1227}, doi = {10.1016/j.cell.2018.02.015}, pmid = {29522743}, issn = {1097-4172}, support = {R01 GM099538/GM/NIGMS NIH HHS/United States ; T32 DK077653/DK/NIDDK NIH HHS/United States ; R01 AI123394/AI/NIAID NIH HHS/United States ; R01 HD092414/HD/NICHD NIH HHS/United States ; T32 GM007067/GM/NIGMS NIH HHS/United States ; }, abstract = {The composite members of the microbiota face a range of selective pressures and must adapt to persist in the host. We highlight recent work characterizing the evolution and transfer of genetic information across nested scales of host-associated microbiota, which enable resilience to biotic and abiotic perturbations. At the strain level, we consider the preservation and diversification of adaptive information in progeny lineages. At the community level, we consider genetic exchange between distinct microbes in the ecosystem. Finally, we frame microbiomes as open systems subject to acquisition of novel information from foreign ecosystems through invasion by outsider microbes.}, } @article {pmid29522739, year = {2018}, author = {Blaser, MJ}, title = {The Past and Future Biology of the Human Microbiome in an Age of Extinctions.}, journal = {Cell}, volume = {172}, number = {6}, pages = {1173-1177}, doi = {10.1016/j.cell.2018.02.040}, pmid = {29522739}, issn = {1097-4172}, abstract = {The evolutionary fate of humans is intimately linked with that of our microbiome. Medical and technological advances have caused large-scale changes in the composition and maturation of human-associated microbial communities, increasing our susceptibility to infectious and developmental diseases. Restoration of the human microbiome must become a priority for biomedicine.}, } @article {pmid29518346, year = {2018}, author = {Solbiati, J and Frias-Lopez, J}, title = {Metatranscriptome of the Oral Microbiome in Health and Disease.}, journal = {Journal of dental research}, volume = {97}, number = {5}, pages = {492-500}, doi = {10.1177/0022034518761644}, pmid = {29518346}, issn = {1544-0591}, support = {R01 DE021553/DE/NIDCR NIH HHS/United States ; }, abstract = {The last few decades have witnessed an increasing interest in studying the human microbiome and its role in health and disease. The focus of those studies was mainly the characterization of changes in the composition of the microbial communities under different conditions. As a result of those studies, we now know that imbalance in the composition of the microbiome, also referred to as microbial dysbiosis, is directly linked to developing certain conditions. Dysbiosis of the oral microbiome is a prime example of how this imbalance leads to disease in the case of periodontal disease. However, there is considerable overlap in the phylogenetic profiles of microbial communities associated with active and inactive lesions, suggesting that the difference in periodontal status of those sites may not be explained solely by differences in the subgingival microbial composition. These findings suggest that differences in functional activities may be the essential elements that define the dysbiotic process. Researchers have recently begun to study gene expression of the oral microbiome in situ with the goal of identifying changes in functional activities that could explain the transition from health to disease. These initial results suggest that, rather than a specific composition, a better understanding of oral dysbiosis can be obtained from the study of functional activities of the microbial community. In this review, we give a summary of these initial studies, which have opened a new door to our understanding of the dynamics of the oral community during the dysbiotic process in the oral cavity.}, } @article {pmid29507896, year = {2018}, author = {Stagaman, K and Cepon-Robins, TJ and Liebert, MA and Gildner, TE and Urlacher, SS and Madimenos, FC and Guillemin, K and Snodgrass, JJ and Sugiyama, LS and Bohannan, BJM}, title = {Market Integration Predicts Human Gut Microbiome Attributes across a Gradient of Economic Development.}, journal = {mSystems}, volume = {3}, number = {1}, pages = {}, doi = {10.1128/mSystems.00122-17}, pmid = {29507896}, issn = {2379-5077}, support = {P50 GM098911/GM/NIGMS NIH HHS/United States ; T32 GM007413/GM/NIGMS NIH HHS/United States ; }, abstract = {Economic development is marked by dramatic increases in the incidence of microbiome-associated diseases, such as autoimmune diseases and metabolic syndromes, but the lifestyle changes that drive alterations in the human microbiome are not known. We measured market integration as a proxy for economically related lifestyle attributes, such as ownership of specific market goods that index degree of market integration and components of traditional and nontraditional (more modern) house structure and infrastructure, and profiled the fecal microbiomes of 213 participants from a contiguous, indigenous Ecuadorian population. Despite relatively modest differences in lifestyle across the population, greater economic development correlated with significantly lower within-host diversity, higher between-host dissimilarity, and a decrease in the relative abundance of the bacterium Prevotella. These microbiome shifts were most strongly associated with more modern housing, followed by reduced ownership of traditional subsistence lifestyle-associated items. IMPORTANCE Previous research has reported differences in the gut microbiome between populations residing in wealthy versus poorer countries, leading to the assertion that lifestyle changes associated with economic development promote changes in the gut microbiome that promote the proliferation of microbiome-associated diseases. However, a direct relationship between economic development and the gut microbiome has not previously been shown. We surveyed the gut microbiomes of a single indigenous population undergoing economic development and found significant associations between features of the gut microbiome and lifestyle changes associated with economic development. These findings suggest that even the earliest stages of economic development can drive changes in the gut microbiome, which may provide a warning sign for the development of microbiome-associated diseases.}, } @article {pmid29492330, year = {2017}, author = {Lang, JM and Coil, DA and Neches, RY and Brown, WE and Cavalier, D and Severance, M and Hampton-Marcell, JT and Gilbert, JA and Eisen, JA}, title = {A microbial survey of the International Space Station (ISS).}, journal = {PeerJ}, volume = {5}, number = {}, pages = {e4029}, doi = {10.7717/peerj.4029}, pmid = {29492330}, issn = {2167-8359}, support = {P30 DK042086/DK/NIDDK NIH HHS/United States ; }, abstract = {Background: Modern advances in sequencing technology have enabled the census of microbial members of many natural ecosystems. Recently, attention is increasingly being paid to the microbial residents of human-made, built ecosystems, both private (homes) and public (subways, office buildings, and hospitals). Here, we report results of the characterization of the microbial ecology of a singular built environment, the International Space Station (ISS). This ISS sampling involved the collection and microbial analysis (via 16S rDNA PCR) of 15 surfaces sampled by swabs onboard the ISS. This sampling was a component of Project MERCCURI (Microbial Ecology Research Combining Citizen and University Researchers on ISS). Learning more about the microbial inhabitants of the "buildings" in which we travel through space will take on increasing importance, as plans for human exploration continue, with the possibility of colonization of other planets and moons.

Results: Sterile swabs were used to sample 15 surfaces onboard the ISS. The sites sampled were designed to be analogous to samples collected for (1) the Wildlife of Our Homes project and (2) a study of cell phones and shoes that were concurrently being collected for another component of Project MERCCURI. Sequencing of the 16S rDNA genes amplified from DNA extracted from each swab was used to produce a census of the microbes present on each surface sampled. We compared the microbes found on the ISS swabs to those from both homes on Earth and data from the Human Microbiome Project.

Conclusions: While significantly different from homes on Earth and the Human Microbiome Project samples analyzed here, the microbial community composition on the ISS was more similar to home surfaces than to the human microbiome samples. The ISS surfaces are species-rich with 1,036-4,294 operational taxonomic units (OTUs per sample). There was no discernible biogeography of microbes on the 15 ISS surfaces, although this may be a reflection of the small sample size we were able to obtain.}, } @article {pmid29490879, year = {2018}, author = {Wu, WK and Chen, CC and Panyod, S and Chen, RA and Wu, MS and Sheen, LY and Chang, SC}, title = {Optimization of fecal sample processing for microbiome study - The journey from bathroom to bench.}, journal = {Journal of the Formosan Medical Association = Taiwan yi zhi}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jfma.2018.02.005}, pmid = {29490879}, issn = {0929-6646}, abstract = {Although great interest has been displayed by researchers in the contribution of gut microbiota to human health, there is still no standard protocol with consensus to guarantee the sample quality of metagenomic analysis. Here we reviewed existing methodology studies and present suggestions for optimizing research pipeline from fecal sample collection to DNA extraction. First, we discuss strategies of clinical metadata collection as common confounders for microbiome research. Second, we propose general principles for freshly collected fecal sample and its storage and share a DIY stool collection kit protocol based on the manual procedure of Human Microbiome Project (HMP). Third, we provide a useful information of collection kit with DNA stabilization buffers and compare their pros and cons for multi-omic study. Fourth, we offer technical strategies as well as information of novel tools for sample aliquoting before long-term storage. Fifth, we discuss the substantial impact of different DNA extraction protocols on technical variations of metagenomic analysis. And lastly, we point out the limitation of current methods and the unmet needs for better quality control of metagenomic analysis. We hope the information provided here will help investigators in this exciting field to advance their studies while avoiding experimental artifacts.}, } @article {pmid29488821, year = {2018}, author = {Hakansson, AP and Orihuela, CJ and Bogaert, D}, title = {Bacterial-Host Interactions: Physiology and Pathophysiology of Respiratory Infection.}, journal = {Physiological reviews}, volume = {98}, number = {2}, pages = {781-811}, doi = {10.1152/physrev.00040.2016}, pmid = {29488821}, issn = {1522-1210}, abstract = {It has long been thought that respiratory infections are the direct result of acquisition of pathogenic viruses or bacteria, followed by their overgrowth, dissemination, and in some instances tissue invasion. In the last decades, it has become apparent that in contrast to this classical view, the majority of microorganisms associated with respiratory infections and inflammation are actually common members of the respiratory ecosystem and only in rare circumstances do they cause disease. This suggests that a complex interplay between host, environment, and properties of colonizing microorganisms together determines disease development and its severity. To understand the pathophysiological processes that underlie respiratory infectious diseases, it is therefore necessary to understand the host-bacterial interactions occurring at mucosal surfaces, along with the microbes inhabiting them, during symbiosis. Current knowledge regarding host-bacterial interactions during asymptomatic colonization will be discussed, including a plausible role for the human microbiome in maintaining a healthy state. With this as a starting point, we will discuss possible disruptive factors contributing to dysbiosis, which is likely to be a key trigger for pathobionts in the development and pathophysiology of respiratory diseases. Finally, from this renewed perspective, we will reflect on current and potential new approaches for treatment in the future.}, } @article {pmid29475860, year = {2018}, author = {Daisley, BA and Trinder, M and McDowell, TW and Collins, SL and Sumarah, MW and Reid, G}, title = {Microbiota-Mediated Modulation of Organophosphate Insecticide Toxicity by Species-Dependent Interactions with Lactobacilli in a Drosophila melanogaster Insect Model.}, journal = {Applied and environmental microbiology}, volume = {84}, number = {9}, pages = {}, doi = {10.1128/AEM.02820-17}, pmid = {29475860}, issn = {1098-5336}, abstract = {Despite the benefits to the global food supply and agricultural economies, pesticides are believed to pose a threat to the health of both humans and wildlife. Chlorpyrifos (CP), a commonly used organophosphate insecticide, has poor target specificity and causes acute neurotoxicity in a wide range of species via the suppression of acetylcholinesterase. This effect is exacerbated 10- to 100-fold by chlorpyrifos oxon (CPO), a principal metabolite of CP. Since many animal-associated symbiont microorganisms are known to hydrolyze CP into CPO, we used a Drosophila melanogaster insect model to investigate the hypothesis that indigenous and probiotic bacteria could affect CP metabolism and toxicity. Antibiotic-treated and germfree D. melanogaster insects lived significantly longer than their conventionally reared counterparts when exposed to 10 μM CP. Drosophila melanogaster gut-derived Lactobacillus plantarum, but not Acetobacterindonesiensis, was shown to metabolize CP. Liquid chromatography tandem-mass spectrometry confirmed that the L. plantarum isolate preferentially metabolized CP into CPO when grown in CP-spiked culture medium. Further experiments showed that monoassociating germfree D. melanogaster with the L. plantarum isolate could reestablish a conventional-like sensitivity to CP. Interestingly, supplementation with the human probiotic Lactobacillus rhamnosus GG (a strain that binds but does not metabolize CP) significantly increased the survival of the CP-exposed germfree D. melanogaster This suggests strain-specific differences in CP metabolism may exist among lactobacilli and emphasizes the need for further investigation. In summary, these results suggest that (i) CPO formation by the gut microbiota can have biologically relevant consequences for the host, and (ii) probiotic lactobacilli may be beneficial in reducing in vivo CP toxicity.IMPORTANCE An understudied area of research is how the microbiota (microorganisms living in/on an animal) affects the metabolism and toxic outcomes of environmental pollutants such as pesticides. This study focused specifically on how the microbial biotransformation of chlorpyrifos (CP; a common organophosphate insecticide) affected host exposure and toxicity parameters in a Drosophila melanogaster insect model. Our results demonstrate that the biotransformation of CP by the gut microbiota had biologically relevant and toxic consequences on host health and that certain probiotic lactobacilli may be beneficial in reducing CP toxicity. Since inadvertent pesticide exposure is suspected to negatively impact the health of off-target species, these findings may provide useful information for wildlife conservation and environmental sustainability planning. Furthermore, the results highlight the need to consider microbiota composition differences between beneficial and pest insects in future insecticide designs. More broadly, this study supports the use of beneficial microorganisms to modulate the microbiota-mediated biotransformation of xenobiotics.}, } @article {pmid29471863, year = {2018}, author = {Petrosino, JF}, title = {The microbiome in precision medicine: the way forward.}, journal = {Genome medicine}, volume = {10}, number = {1}, pages = {12}, doi = {10.1186/s13073-018-0525-6}, pmid = {29471863}, issn = {1756-994X}, support = {R01 AI108588/AI/NIAID NIH HHS/United States ; HHSN267200700014C/DK/NIDDK NIH HHS/United States ; R01 MH112356/MH/NIMH NIH HHS/United States ; U19 AI116497/AI/NIAID NIH HHS/United States ; P30 DK056338/DK/NIDDK NIH HHS/United States ; }, abstract = {Novel associations between the human microbiome and health and disease are routinely emerging, and important host-microbiome interactions are targets for new diagnostics and therapeutics. Understanding how broadly host-microbe associations are maintained across populations is revealing individualized host-microbiome phenotypes that can be integrated with other 'omics' data sets to enhance precision medicine.}, } @article {pmid29467286, year = {2018}, author = {Altindis, E and Cai, W and Sakaguchi, M and Zhang, F and GuoXiao, W and Liu, F and De Meyts, P and Gelfanov, V and Pan, H and DiMarchi, R and Kahn, CR}, title = {Viral insulin-like peptides activate human insulin and IGF-1 receptor signaling: A paradigm shift for host-microbe interactions.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {10}, pages = {2461-2466}, doi = {10.1073/pnas.1721117115}, pmid = {29467286}, issn = {1091-6490}, support = {P30 DK036836/DK/NIDDK NIH HHS/United States ; R01 DK033201/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Cell Line ; Cell Proliferation ; Glucose/metabolism ; Hepatocytes ; Host-Pathogen Interactions/*physiology ; Humans ; Insulin/genetics/*metabolism ; Insulin-Like Growth Factor I/*metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Receptor, IGF Type 1/*metabolism ; Signal Transduction ; Viral Proteins/genetics/*metabolism ; Virus Diseases/virology ; Viruses/*genetics ; }, abstract = {Viruses are the most abundant biological entities and carry a wide variety of genetic material, including the ability to encode host-like proteins. Here we show that viruses carry sequences with significant homology to several human peptide hormones including insulin, insulin-like growth factors (IGF)-1 and -2, FGF-19 and -21, endothelin-1, inhibin, adiponectin, and resistin. Among the strongest homologies were those for four viral insulin/IGF-1-like peptides (VILPs), each encoded by a different member of the family Iridoviridae VILPs show up to 50% homology to human insulin/IGF-1, contain all critical cysteine residues, and are predicted to form similar 3D structures. Chemically synthesized VILPs can bind to human and murine IGF-1/insulin receptors and stimulate receptor autophosphorylation and downstream signaling. VILPs can also increase glucose uptake in adipocytes and stimulate the proliferation of fibroblasts, and injection of VILPs into mice significantly lowers blood glucose. Transfection of mouse hepatocytes with DNA encoding a VILP also stimulates insulin/IGF-1 signaling and DNA synthesis. Human microbiome studies reveal the presence of these Iridoviridae in blood and fecal samples. Thus, VILPs are members of the insulin/IGF superfamily with the ability to be active on human and rodent cells, raising the possibility for a potential role of VILPs in human disease. Furthermore, since only 2% of viruses have been sequenced, this study raises the potential for discovery of other viral hormones which, along with known virally encoded growth factors, may modify human health and disease.}, } @article {pmid29453029, year = {2018}, author = {Peñalver Bernabé, B and Cralle, L and Gilbert, JA}, title = {Systems biology of the human microbiome.}, journal = {Current opinion in biotechnology}, volume = {51}, number = {}, pages = {146-153}, doi = {10.1016/j.copbio.2018.01.018}, pmid = {29453029}, issn = {1879-0429}, abstract = {Recent research has shown that the microbiome-a collection of microorganisms, including bacteria, fungi, and viruses, living on and in a host-are of extraordinary importance in human health, even from conception and development in the uterus. Therefore, to further our ability to diagnose disease, to predict treatment outcomes, and to identify novel therapeutics, it is essential to include microbiome and microbial metabolic biomarkers in Systems Biology investigations. In clinical studies or, more precisely, Systems Medicine approaches, we can use the diversity and individual characteristics of the personal microbiome to enhance our resolution for patient stratification. In this review, we explore several Systems Medicine approaches, including Microbiome Wide Association Studies to understand the role of the human microbiome in health and disease, with a focus on 'preventive medicine' or P4 (i.e., personalized, predictive, preventive, participatory) medicine.}, } @article {pmid29447696, year = {2018}, author = {Smillie, CS and Sauk, J and Gevers, D and Friedman, J and Sung, J and Youngster, I and Hohmann, EL and Staley, C and Khoruts, A and Sadowsky, MJ and Allegretti, JR and Smith, MB and Xavier, RJ and Alm, EJ}, title = {Strain Tracking Reveals the Determinants of Bacterial Engraftment in the Human Gut Following Fecal Microbiota Transplantation.}, journal = {Cell host & microbe}, volume = {23}, number = {2}, pages = {229-240.e5}, doi = {10.1016/j.chom.2018.01.003}, pmid = {29447696}, issn = {1934-6069}, mesh = {Biodiversity ; Clostridium Infections/*prevention & control/therapy ; Clostridium difficile/*growth & development ; Fecal Microbiota Transplantation/*methods ; Gastrointestinal Microbiome/*physiology ; Gastrointestinal Tract/*microbiology ; Humans ; Models, Biological ; Recurrence ; Secondary Prevention/*methods ; }, abstract = {Fecal microbiota transplantation (FMT) from healthy donor to patient is a treatment for microbiome-associated diseases. Although the success of FMT requires donor bacteria to engraft in the patient's gut, the forces governing engraftment in humans are unknown. Here we use an ongoing clinical experiment, the treatment of recurrent Clostridium difficile infection, to uncover the rules of engraftment in humans. We built a statistical model that predicts which bacterial species will engraft in a given host, and developed Strain Finder, a method to infer strain genotypes and track them over time. We find that engraftment can be predicted largely from the abundance and phylogeny of bacteria in the donor and the pre-FMT patient. Furthermore, donor strains within a species engraft in an all-or-nothing manner and previously undetected strains frequently colonize patients receiving FMT. We validated these findings for metabolic syndrome, suggesting that the same principles of engraftment extend to other indications.}, } @article {pmid29447068, year = {2018}, author = {Diop, K and Diop, A and Levasseur, A and Mediannikov, O and Robert, C and Armstrong, N and Couderc, C and Bretelle, F and Raoult, D and Fournier, PE and Fenollar, F}, title = {Microbial Culturomics Broadens Human Vaginal Flora Diversity: Genome Sequence and Description of Prevotella lascolaii sp. nov. Isolated from a Patient with Bacterial Vaginosis.}, journal = {Omics : a journal of integrative biology}, volume = {22}, number = {3}, pages = {210-222}, doi = {10.1089/omi.2017.0151}, pmid = {29447068}, issn = {1557-8100}, abstract = {Microbial culturomics is a new subfield of postgenomic medicine and omics biotechnology application that has broadened our awareness on bacterial diversity of the human microbiome, including the human vaginal flora bacterial diversity. Using culturomics, a new obligate anaerobic Gram-stain-negative rod-shaped bacterium designated strain khD1T was isolated in the vagina of a patient with bacterial vaginosis and characterized using taxonogenomics. The most abundant cellular fatty acids were C15:0 anteiso (36%), C16:0 (19%), and C15:0 iso (10%). Based on an analysis of the full-length 16S rRNA gene sequences, phylogenetic analysis showed that the strain khD1T exhibited 90% sequence similarity with Prevotella loescheii, the phylogenetically closest validated Prevotella species. With 3,763,057 bp length, the genome of strain khD1T contained (mol%) 48.7 G + C and 3248 predicted genes, including 3194 protein-coding and 54 RNA genes. Given the phenotypical and biochemical characteristic results as well as genome sequencing, strain khD1T is considered to represent a novel species within the genus Prevotella, for which the name Prevotella lascolaii sp. nov. is proposed. The type strain is khD1T (= CSUR P0109, = DSM 101754). These results show that microbial culturomics greatly improves the characterization of the human microbiome repertoire by isolating potential putative new species. Further studies will certainly clarify the microbial mechanisms of pathogenesis of these new microbes and their role in health and disease. Microbial culturomics is an important new addition to the diagnostic medicine toolbox and warrants attention in future medical, global health, and integrative biology postgraduate teaching curricula.}, } @article {pmid29444477, year = {2018}, author = {Simões-Silva, L and Araujo, R and Pestana, M and Soares-Silva, I and Sampaio-Maia, B}, title = {The microbiome in chronic kidney disease patients undergoing hemodialysis and peritoneal dialysis.}, journal = {Pharmacological research}, volume = {130}, number = {}, pages = {143-151}, doi = {10.1016/j.phrs.2018.02.011}, pmid = {29444477}, issn = {1096-1186}, abstract = {Chronic kidney disease (CKD) is associated with an imbalanced human microbiome due not only to CKD-associated factors such as uremia, increased inflammation and immunosuppression, but also to pharmacological therapies and dietary restrictions. End-stage renal disease patients require renal replacement therapies commonly in the form of hemodialysis (HD) or peritoneal dialysis (PD). HD implies the existence of a vascular access, such as an arteriovenous fistula/graft or a venous catheter, whereas PD implies a long-term peritoneal catheter and the constant inflow of peritoneal dialysate. Also, dietary adaptations are mandatory in both therapies. This revision explores the impact of HD or PD therapies on human microbiome. HD and PD appear to be associated with different changes in the gut microbiome, for example a decrease in Proteobacteria relative abundance in HD patients and increase in PD patients. Both therapies may also have an impact on the human microbiome beyond the gut, leading to increased relative abundance of specific bacteria in the blood microbiome of HD patients and increased relative abundance of other bacteria in the peritoneal microbiome of PD patients. HD and PD catheter biofilms may also play an important role in the changes observed in these microbiomes. A more interdisciplinary approach is needed to further clarify the role of microbial groups other than bacteria in all body habitats to allow the complete understanding of the impact of HD or PD on the microbiome of CKD patients. Moreover, strategies that promote a healthy balance of the human microbiome on these patients should be explored.}, } @article {pmid29444186, year = {2018}, author = {Donovan, PD and Gonzalez, G and Higgins, DG and Butler, G and Ito, K}, title = {Identification of fungi in shotgun metagenomics datasets.}, journal = {PloS one}, volume = {13}, number = {2}, pages = {e0192898}, doi = {10.1371/journal.pone.0192898}, pmid = {29444186}, issn = {1932-6203}, mesh = {Animals ; Antarctic Regions ; Ascomycota/classification/genetics/isolation & purification ; Candida tropicalis/genetics/pathogenicity ; Databases, Genetic ; Fungi/classification/*genetics/pathogenicity ; Humans ; Metagenome ; *Metagenomics ; Mice ; Microbiota/genetics ; Phylogeny ; Soil Microbiology ; Swine ; Zoonoses/microbiology ; }, abstract = {Metagenomics uses nucleic acid sequencing to characterize species diversity in different niches such as environmental biomes or the human microbiome. Most studies have used 16S rRNA amplicon sequencing to identify bacteria. However, the decreasing cost of sequencing has resulted in a gradual shift away from amplicon analyses and towards shotgun metagenomic sequencing. Shotgun metagenomic data can be used to identify a wide range of species, but have rarely been applied to fungal identification. Here, we develop a sequence classification pipeline, FindFungi, and use it to identify fungal sequences in public metagenome datasets. We focus primarily on animal metagenomes, especially those from pig and mouse microbiomes. We identified fungi in 39 of 70 datasets comprising 71 fungal species. At least 11 pathogenic species with zoonotic potential were identified, including Candida tropicalis. We identified Pseudogymnoascus species from 13 Antarctic soil samples initially analyzed for the presence of bacteria capable of degrading diesel oil. We also show that Candida tropicalis and Candida loboi are likely the same species. In addition, we identify several examples where contaminating DNA was erroneously included in fungal genome assemblies.}, } @article {pmid29440648, year = {2018}, author = {Stokholm, J and Blaser, MJ and Thorsen, J and Rasmussen, MA and Waage, J and Vinding, RK and Schoos, AM and Kunøe, A and Fink, NR and Chawes, BL and Bønnelykke, K and Brejnrod, AD and Mortensen, MS and Al-Soud, WA and Sørensen, SJ and Bisgaard, H}, title = {Publisher Correction: Maturation of the gut microbiome and risk of asthma in childhood.}, journal = {Nature communications}, volume = {9}, number = {1}, pages = {704}, doi = {10.1038/s41467-018-03150-x}, pmid = {29440648}, issn = {2041-1723}, abstract = {The originally published version of this Article contained an incorrect version of Figure 3 that was introduced following peer review and inadvertently not corrected during the production process. Both versions contain the same set of abundance data, but the incorrect version has the children's asthma status erroneously disconnected from the abundance data, thereby producing the non-representative p values and graphic presentations. These errors have now been rectified, with the correct version of Figure 3 replaced in both the PDF and HTML versions of the Article.}, } @article {pmid29430070, year = {2017}, author = {Ren, B and Bacallado, S and Favaro, S and Holmes, S and Trippa, L}, title = {Bayesian Nonparametric Ordination for the Analysis of Microbial Communities.}, journal = {Journal of the American Statistical Association}, volume = {112}, number = {520}, pages = {1430-1442}, doi = {10.1080/01621459.2017.1288631}, pmid = {29430070}, issn = {0162-1459}, support = {R01 AI112401/AI/NIAID NIH HHS/United States ; }, abstract = {Human microbiome studies use sequencing technologies to measure the abundance of bacterial species or Operational Taxonomic Units (OTUs) in samples of biological material. Typically the data are organized in contingency tables with OTU counts across heterogeneous biological samples. In the microbial ecology community, ordination methods are frequently used to investigate latent factors or clusters that capture and describe variations of OTU counts across biological samples. It remains important to evaluate how uncertainty in estimates of each biological sample's microbial distribution propagates to ordination analyses, including visualization of clusters and projections of biological samples on low dimensional spaces. We propose a Bayesian analysis for dependent distributions to endow frequently used ordinations with estimates of uncertainty. A Bayesian nonparametric prior for dependent normalized random measures is constructed, which is marginally equivalent to the normalized generalized Gamma process, a well-known prior for nonparametric analyses. In our prior, the dependence and similarity between microbial distributions is represented by latent factors that concentrate in a low dimensional space. We use a shrinkage prior to tune the dimensionality of the latent factors. The resulting posterior samples of model parameters can be used to evaluate uncertainty in analyses routinely applied in microbiome studies. Specifically, by combining them with multivariate data analysis techniques we can visualize credible regions in ecological ordination plots. The characteristics of the proposed model are illustrated through a simulation study and applications in two microbiome datasets.}, } @article {pmid29425888, year = {2018}, author = {Rajpoot, M and Sharma, AK and Sharma, A and Gupta, GK}, title = {Understanding the microbiome: Emerging biomarkers for exploiting the microbiota for personalized medicine against cancer.}, journal = {Seminars in cancer biology}, volume = {52}, number = {Pt 1}, pages = {1-8}, doi = {10.1016/j.semcancer.2018.02.003}, pmid = {29425888}, issn = {1096-3650}, abstract = {The human body is a home to more than 1 trillion microbes with a diverse variety of commensal microbes that play a crucial role towards the health of the individual. These microbes occupy different habitats such as gut, skin, vagina, oral etc. Not only the types and abundance of microbes are different in different organs, but also these may differ in different individuals. The genome of these microbiota and their ecosystem constitute to form a microbiome. Factors such as diet, environment, host genetics etc. may be the reason behind the wide microbial diversity. A number of studies performed on human microbiome have revealed that microbiota present in healthy and diseased individuals are distinct. Altered microbiome is many a times the reason behind the overexpression of genes which may cause complex diseases including cancer. Manipulation of the human microbiome can be done by microbial supplements such as probiotics or synbiotics, diet or prebiotics and microbial suppression strategies using antibiotics. Recent advances in genome sequencing technologies and metagenomic analysis provide us the broader understanding of these commensal microbes and highlighting the distinctive features of microbiome during healthy and disease states. Molecular pathological epidemiology (MPE) studies have been very helpful in providing insights into the pathological process behind disease evolution and progression by determining the specific etiological factors. New emerging field of research targets the microbiome for therapeutic purposes by which personalized medicines can be made for treating various types of tumors. Screening programmes might be helpful in identifying patients who are at the verge of developing cancer and in delivering appropriate approaches according to individual risk modes so that disease could be prevented.}, } @article {pmid29416567, year = {2018}, author = {Liang, D and Leung, RK and Guan, W and Au, WW}, title = {Involvement of gut microbiome in human health and disease: brief overview, knowledge gaps and research opportunities.}, journal = {Gut pathogens}, volume = {10}, number = {}, pages = {3}, doi = {10.1186/s13099-018-0230-4}, pmid = {29416567}, issn = {1757-4749}, abstract = {The commensal, symbiotic, and pathogenic microbial community which resides inside our body and on our skin (the human microbiome) can perturb host energy metabolism and immunity, and thus significantly influence development of a variety of human diseases. Therefore, the field has attracted unprecedented attention in the last decade. Although a large amount of data has been generated, there are still many unanswered questions and no universal agreements on how microbiome affects human health have been agreed upon. Consequently, this review was written to provide an updated overview of the rapidly expanding field, with a focus on revealing knowledge gaps and research opportunities. Specifically, the review covered animal physiology, optimal microbiome standard, health intervention by manipulating microbiome, knowledge base building by text mining, microbiota community structure and its implications in human diseases and health monitoring by analyzing microbiome in the blood. The review should enhance interest in conducting novel microbiota investigations that will further improve health and therapy.}, } @article {pmid29413172, year = {2018}, author = {Krittanawong, C}, title = {Big Data Analytics, the Microbiome, Host-omic and Bug-omic Data and Risk for Cardiovascular Disease.}, journal = {Heart, lung & circulation}, volume = {27}, number = {3}, pages = {e26-e27}, doi = {10.1016/j.hlc.2017.07.012}, pmid = {29413172}, issn = {1444-2892}, mesh = {Cardiovascular Diseases/*epidemiology ; Databases, Factual ; Global Health ; Humans ; *Microbiota ; Morbidity/trends ; Risk Assessment/*statistics & numerical data ; Risk Factors ; }, } @article {pmid29392389, year = {2018}, author = {Reen, FJ and Gutiérrez-Barranquero, JA and Parages, ML and O Gara, F}, title = {Coumarin: a novel player in microbial quorum sensing and biofilm formation inhibition.}, journal = {Applied microbiology and biotechnology}, volume = {102}, number = {5}, pages = {2063-2073}, doi = {10.1007/s00253-018-8787-x}, pmid = {29392389}, issn = {1432-0614}, support = {FP7-PEOPLE-2013-ITN, 607786; FP7-KBBE-2012-6, CP-TP-312184; FP7-KBBE-2012-6, 311975; OCEAN 2011-2, 287589; Marie Curie 256596; EU-634486//European Commission/ ; SSPC-2, 12/RC/2275; 13/TIDA/B2625; 12/TIDA/B2411; 12/TIDA/B2405; 14/TIDA/2438, 15/TIDA/2977//Science Foundation Ireland/Ireland ; FIRM/RSF/CoFoRD; FIRM 08/RDC/629; FIRM 1/F009/MabS; FIRM 13/F/516//Department of Agriculture, Food and the Marine/ ; PD/2011/2414; GOIPG/2014/647//Irish Research Council for Science, Engineering and Technology/ ; MRCG-2014-6//Health Research Board/Ireland ; Beaufort award C2CRA 2007/082//Marine Institute/ ; Walsh Fellowship 2013//Teagasc/ ; CF-2017-0757-P//Enterprise Ireland/ ; }, mesh = {Animals ; Anti-Bacterial Agents/*pharmacology ; Bacteria/*drug effects ; Bacterial Infections/drug therapy/*microbiology ; Bacterial Physiological Phenomena/drug effects ; Biofilms/*drug effects ; Coumarins/*pharmacology ; Humans ; Quorum Sensing/*drug effects ; }, abstract = {Antibiotic resistance is a growing threat worldwide, causing serious problems in the treatment of microbial infections. The discovery and development of new drugs is urgently needed to overcome this problem which has greatly undermined the clinical effectiveness of conventional antibiotics. An intricate cell-cell communication system termed quorum sensing (QS) and the coordinated multicellular behaviour of biofilm formation have both been identified as promising targets for the treatment and clinical management of microbial infections. QS systems allow bacteria to adapt rapidly to harsh conditions, and are known to promote the formation of antibiotic tolerant biofilm communities. It is well known that biofilm is a recalcitrant mode of growth and it also increases bacterial resistance to conventional antibiotics. The pharmacological properties of coumarins have been well described, and these have included several that possess antimicrobial properties. More recently, reports have highlighted the potential role of coumarins as alternative therapeutic strategies based on their ability to block the QS signalling systems and to inhibit the formation of biofilms in clinically relevant pathogens. In addition to human infections, coumarins have also been found to be effective in controlling plant pathogens, infections in aquaculture, food spoilage and in reducing biofouling caused by eukaryotic organisms. Thus, the coumarin class of small molecule natural product are emerging as a promising strategy to combat bacterial infections in the new era of antimicrobial resistance.}, } @article {pmid29383197, year = {2017}, author = {Phelan, JP and Reen, FJ and Caparros-Martin, JA and O'Connor, R and O'Gara, F}, title = {Rethinking the bile acid/gut microbiome axis in cancer.}, journal = {Oncotarget}, volume = {8}, number = {70}, pages = {115736-115747}, doi = {10.18632/oncotarget.22803}, pmid = {29383197}, issn = {1949-2553}, abstract = {Dietary factors, probiotic agents, aging and antibiotics/medicines impact on gut microbiome composition leading to disturbances in localised microbial populations. The impact can be profound and underlies a plethora of human disorders, including the focus of this review; cancer. Compromised microbiome populations can alter bile acid signalling and produce distinct pathophysiological bile acid profiles. These in turn have been associated with cancer development and progression. Exposure to high levels of bile acids, combined with localised molecular/genome instability leads to the acquisition of bile mediated neoplastic alterations, generating apoptotic resistant proliferation phenotypes. However, in recent years, several studies have emerged advocating the therapeutic benefits of bile acid signalling in suppressing molecular and phenotypic hallmarks of cancer progression. These studies suggest that in some instances, bile acids may reduce cancer phenotypic effects, thereby limiting metastatic potential. In this review, we contextualise the current state of the art to propose that the bile acid/gut microbiome axis can influence cancer progression to the extent that classical in vitro cancer hallmarks of malignancy (cell invasion, cell migration, clonogenicity, and cell adhesion) are significantly reduced. We readily acknowledge the existence of a bile acid/gut microbiome axis in cancer initiation, however, in light of recent advances, we focus exclusively on the role of bile acids as potentially beneficial molecules in suppressing cancer progression. Finally, we theorise that suppressing aggressive malignant phenotypes through bile acid/gut microbiome axis modulation could uncover new and innovative disease management strategies for managing cancers in vulnerable cohorts.}, } @article {pmid29382863, year = {2018}, author = {Di Francesco, L and Verrico, A and Asteriti, IA and Rovella, P and Cirigliano, P and Guarguaglini, G and Schininà, ME and Lavia, P}, title = {Visualization of human karyopherin beta-1/importin beta-1 interactions with protein partners in mitotic cells by co-immunoprecipitation and proximity ligation assays.}, journal = {Scientific reports}, volume = {8}, number = {1}, pages = {1850}, doi = {10.1038/s41598-018-19351-9}, pmid = {29382863}, issn = {2045-2322}, abstract = {Karyopherin beta-1/Importin beta-1 is a conserved nuclear transport receptor, acting in protein nuclear import in interphase and as a global regulator of mitosis. These pleiotropic functions reflect its ability to interact with, and regulate, different pathways during the cell cycle, operating as a major effector of the GTPase RAN. Importin beta-1 is overexpressed in cancers characterized by high genetic instability, an observation that highlights the importance of identifying its partners in mitosis. Here we present the first comprehensive profile of importin beta-1 interactors from human mitotic cells. By combining co-immunoprecipitation and proteome-wide mass spectrometry analysis of synchronized cell extracts, we identified expected (e.g., RAN and SUMO pathway factors) and novel mitotic interactors of importin beta-1, many with RNA-binding ability, that had not been previously associated with importin beta-1. These data complement interactomic studies of interphase transport pathways. We further developed automated proximity ligation assay (PLA) protocols to validate selected interactors. We succeeded in obtaining spatial and temporal resolution of genuine importin beta-1 interactions, which were visualized and localized in situ in intact mitotic cells. Further developments of PLA protocols will be helpful to dissect importin beta-1-orchestrated pathways during mitosis.}, } @article {pmid29382070, year = {2018}, author = {D'Argenio, V}, title = {Human Microbiome Acquisition and Bioinformatic Challenges in Metagenomic Studies.}, journal = {International journal of molecular sciences}, volume = {19}, number = {2}, pages = {}, doi = {10.3390/ijms19020383}, pmid = {29382070}, issn = {1422-0067}, mesh = {*Gastrointestinal Microbiome ; Genomics/*methods/standards ; Humans ; *Metagenome ; Transcriptome ; }, abstract = {The study of the human microbiome has become a very popular topic. Our microbial counterpart, in fact, appears to play an important role in human physiology and health maintenance. Accordingly, microbiome alterations have been reported in an increasing number of human diseases. Despite the huge amount of data produced to date, less is known on how a microbial dysbiosis effectively contributes to a specific pathology. To fill in this gap, other approaches for microbiome study, more comprehensive than 16S rRNA gene sequencing, i.e., shotgun metagenomics and metatranscriptomics, are becoming more widely used. Methods standardization and the development of specific pipelines for data analysis are required to contribute to and increase our understanding of the human microbiome relationship with health and disease status.}, } @article {pmid29379536, year = {2018}, author = {Nobili, V and Putignani, L and Mosca, A and Chierico, FD and Vernocchi, P and Alisi, A and Stronati, L and Cucchiara, S and Toscano, M and Drago, L}, title = {Bifidobacteria and lactobacilli in the gut microbiome of children with non-alcoholic fatty liver disease: which strains act as health players?.}, journal = {Archives of medical science : AMS}, volume = {14}, number = {1}, pages = {81-87}, doi = {10.5114/aoms.2016.62150}, pmid = {29379536}, issn = {1734-1922}, abstract = {Introduction: Non-alcoholic fatty liver disease (NAFLD), considered the leading cause of chronic liver disease in children, can often progress from non-alcoholic fatty liver (NAFL) to non-alcoholic steatohepatitis (NASH). It is clear that obesity is one of the main risk factors involved in NAFLD pathogenesis, even if specific mechanisms have yet to be elucidated. We investigated the distribution of intestinal bifidobacteria and lactobacilli in the stools of four groups of children: obese, obese with NAFL, obese with NASH, and healthy, age-matched controls (CTRLs).

Material and methods: Sixty-one obese, NAFL and NASH children and 54 CTRLs were enrolled in the study. Anthropometric and metabolic parameters were measured for all subjects. All children with suspected NASH underwent liver biopsy. Bifidobacteria and lactobacilli were analysed in children's faecal samples, during a broader, 16S rRNA-based pyrosequencing analysis of the gut microbiome.

Results: Three Bifidobacterium spp. (Bifidobacterium longum, Bifidobacterium bifidum, and Bifidobacterium adolescentis) and five Lactobacillus spp. (L. zeae, L. vaginalis, L. brevis, L. ruminis, and L. mucosae) frequently recurred in metagenomic analyses. Lactobacillus spp. increased in NAFL, NASH, or obese children compared to CTRLs. Particularly, L. mucosae was significantly higher in obese (p = 0.02426), NAFLD (p = 0.01313) and NASH (p = 0.01079) than in CTRLs. In contrast, Bifidobacterium spp. were more abundant in CTRLs, suggesting a protective and beneficial role of these microorganisms against the aforementioned diseases.

Conclusions: Bifidobacteria seem to have a protective role against the development of NAFLD and obesity, highlighting their possible use in developing novel, targeted and effective probiotics.}, } @article {pmid29379216, year = {2018}, author = {Almeida, A and Shao, Y}, title = {Genome watch: Keeping tally in the microbiome.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {3}, pages = {124}, doi = {10.1038/nrmicro.2018.13}, pmid = {29379216}, issn = {1740-1534}, abstract = {This month's Genome Watch highlights how the development of new approaches for quantifying the human microbiome may pave the way for a better understanding of microbial shifts in the context of human health and disease.}, } @article {pmid29378630, year = {2018}, author = {Kolde, R and Franzosa, EA and Rahnavard, G and Hall, AB and Vlamakis, H and Stevens, C and Daly, MJ and Xavier, RJ and Huttenhower, C}, title = {Host genetic variation and its microbiome interactions within the Human Microbiome Project.}, journal = {Genome medicine}, volume = {10}, number = {1}, pages = {6}, doi = {10.1186/s13073-018-0515-8}, pmid = {29378630}, issn = {1756-994X}, support = {U54 DK102557/DK/NIDDK NIH HHS/United States ; U54 HG003067/HG/NHGRI NIH HHS/United States ; P30 DK043351/DK/NIDDK NIH HHS/United States ; 5U54HG003067-13/HG/NHGRI NIH HHS/United States ; U54 DE023798/DE/NIDCR NIH HHS/United States ; }, abstract = {BACKGROUND: Despite the increasing recognition that microbial communities within the human body are linked to health, we have an incomplete understanding of the environmental and molecular interactions that shape the composition of these communities. Although host genetic factors play a role in these interactions, these factors have remained relatively unexplored given the requirement for large population-based cohorts in which both genotyping and microbiome characterization have been performed.

METHODS: We performed whole-genome sequencing of 298 donors from the Human Microbiome Project (HMP) healthy cohort study to accompany existing deep characterization of their microbiomes at various body sites. This analysis yielded an average sequencing depth of 32x, with which we identified 27 million (M) single nucleotide variants and 2.3 M insertions-deletions.

RESULTS: Taxonomic composition and functional potential of the microbiome covaried significantly with genetic principal components in the gastrointestinal tract and oral communities, but not in the nares or vaginal microbiota. Example associations included validation of known associations between FUT2 secretor status, as well as a variant conferring hypolactasia near the LCT gene, with Bifidobacterium longum abundance in stool. The associations of microbial features with both high-level genetic attributes and single variants were specific to particular body sites, highlighting the opportunity to find unique genetic mechanisms controlling microbiome properties in the microbial communities from multiple body sites.

CONCLUSIONS: This study adds deep sequencing of host genomes to the body-wide microbiome sequences already extant from the HMP healthy cohort, creating a unique, versatile, and well-controlled reference for future studies seeking to identify host genetic modulators of the microbiome.}, } @article {pmid29377607, year = {2018}, author = {Bolourian, A and Mojtahedi, Z}, title = {Immunosuppressants produced by Streptomyces: evolution, hygiene hypothesis, tumour rapalog resistance and probiotics.}, journal = {Environmental microbiology reports}, volume = {10}, number = {2}, pages = {123-126}, doi = {10.1111/1758-2229.12617}, pmid = {29377607}, issn = {1758-2229}, abstract = {Resistance to a drug and the suppression of inflammatory disorders with immunosuppressive drugs might have happened upon exposure to natural compounds during evolution. Streptomycetes are soil bacteria, but they produce therapeutic drugs. They have been reported to be the low-abundant members of mucosal microbiomes with a higher prevalence in nonhumans ingesting soil compared with humans. Their lower abundance in the human microbiome might be the representations of our current hygienic lifestyle. We suggest that the Streptomyces bacteria producing antiproliferative/immunosuppressive compounds (e.g., rapamycin and tacrolimus) contribute to the rapalog resistance of certain mucosal tumours (e.g., colon cancer) and the 'hygiene hypothesis'. If so, the shortage of exposure to these compounds in the current lifestyle might be an underlying reason for the increase of inflammatory diseases, such as inflammatory bowel diseases (IBD). An investigation on adding certain Streptomycetes (e.g., S. hygroscopicus and S. tubercidicus) to the list of probiotics against inflammatory diseases would be an interesting research area in the future.}, } @article {pmid29373999, year = {2018}, author = {Fuks, G and Elgart, M and Amir, A and Zeisel, A and Turnbaugh, PJ and Soen, Y and Shental, N}, title = {Combining 16S rRNA gene variable regions enables high-resolution microbial community profiling.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {17}, doi = {10.1186/s40168-017-0396-x}, pmid = {29373999}, issn = {2049-2618}, support = {R01 HL122593/HL/NHLBI NIH HHS/United States ; 3-11174//Ministry of Science and Technology, Israel/International ; }, abstract = {BACKGROUND: Most of our knowledge about the remarkable microbial diversity on Earth comes from sequencing the 16S rRNA gene. The use of next-generation sequencing methods has increased sample number and sequencing depth, but the read length of the most widely used sequencing platforms today is quite short, requiring the researcher to choose a subset of the gene to sequence (typically 16-33% of the total length). Thus, many bacteria may share the same amplified region, and the resolution of profiling is inherently limited. Platforms that offer ultra-long read lengths, whole genome shotgun sequencing approaches, and computational frameworks formerly suggested by us and by others all allow different ways to circumvent this problem yet suffer various shortcomings. There is a need for a simple and low-cost 16S rRNA gene-based profiling approach that harnesses the short read length to provide a much larger coverage of the gene to allow for high resolution, even in harsh conditions of low bacterial biomass and fragmented DNA.

RESULTS: This manuscript suggests Short MUltiple Regions Framework (SMURF), a method to combine sequencing results from different PCR-amplified regions to provide one coherent profiling. The de facto amplicon length is the total length of all amplified regions, thus providing much higher resolution compared to current techniques. Computationally, the method solves a convex optimization problem that allows extremely fast reconstruction and requires only moderate memory. We demonstrate the increase in resolution by in silico simulations and by profiling two mock mixtures and real-world biological samples. Reanalyzing a mock mixture from the Human Microbiome Project achieved about twofold improvement in resolution when combing two independent regions. Using a custom set of six primer pairs spanning about 1200 bp (80%) of the 16S rRNA gene, we were able to achieve ~ 100-fold improvement in resolution compared to a single region, over a mock mixture of common human gut bacterial isolates. Finally, the profiling of a Drosophila melanogaster microbiome using the set of six primer pairs provided a ~ 100-fold increase in resolution and thus enabling efficient downstream analysis.

CONCLUSIONS: SMURF enables the identification of near full-length 16S rRNA gene sequences in microbial communities, having resolution superior compared to current techniques. It may be applied to standard sample preparation protocols with very little modifications. SMURF also paves the way to high-resolution profiling of low-biomass and fragmented DNA, e.g., in the case of formalin-fixed and paraffin-embedded samples, fossil-derived DNA, or DNA exposed to other degrading conditions. The approach is not restricted to combining amplicons of the 16S rRNA gene and may be applied to any set of amplicons, e.g., in multilocus sequence typing (MLST).}, } @article {pmid29373532, year = {2018}, author = {Harper, A and Naghibi, MM and Garcha, D}, title = {The Role of Bacteria, Probiotics and Diet in Irritable Bowel Syndrome.}, journal = {Foods (Basel, Switzerland)}, volume = {7}, number = {2}, pages = {}, doi = {10.3390/foods7020013}, pmid = {29373532}, issn = {2304-8158}, abstract = {Irritable bowel syndrome is a highly prevalent gastrointestinal disorder that threatens the quality of life of millions and poses a substantial financial burden on healthcare systems around the world. Intense research into the human microbiome has led to fascinating discoveries which directly and indirectly implicate the diversity and function of this occult organ in irritable bowel syndrome (IBS) pathophysiology. The benefit of manipulating the gastrointestinal microbiota with diet and probiotics to improve symptoms has been demonstrated in a wealth of both animal and human studies. The positive and negative mechanistic roles bacteria play in IBS will be explored and practical probiotic and dietary choices offered.}, } @article {pmid29359197, year = {2018}, author = {Shaffer, M and Lozupone, C}, title = {Prevalence and Source of Fecal and Oral Bacteria on Infant, Child, and Adult Hands.}, journal = {mSystems}, volume = {3}, number = {1}, pages = {}, doi = {10.1128/mSystems.00192-17}, pmid = {29359197}, issn = {2379-5077}, support = {T15 LM007079/LM/NLM NIH HHS/United States ; }, abstract = {Modern hygienic practices are applied to avoid exposure to pathogens that spread via fecal-oral transmission. Despite this, the gastrointestinal tract is quickly colonized by fecal microbes. The hands are an important vector for the transmission of microbes, but the frequency at which fecal and oral microbes exist on hands and the source of those microbes have not been extensively described. Using data from a previous study that characterized the fecal, oral, and skin microbiota from 73 families, we found a significant incidence of fecal and oral microbes on hands. Of palms, 48.9% had fecal signal and 67.2% had oral signal. Fecal, oral, and forehead microbes were tracked to family members and an individual's own palms far more often than to unrelated individuals and showed relationships with age, gender, and parental status. For instance, oral microbes that were specifically sourced to the same individual (oneself) were most common on infant palms; mothers had more infant-child-sourced and oral-sourced microbes on their palms than nonparents. Fecal microbes on palms more often sourced to members of the family than unrelated individuals, but more often to other members of the family than oneself. This study supports that the hands are an important vector for the transfer of fecal and oral microbes within families. IMPORTANCE Bacteria live all around us, and we are constantly exposed to them during our everyday lives. Modern standards of hygiene aim to limit exposure to fecal bacteria, and yet bacteria rapidly colonize the gut in early life and following antibacterial treatment. Exposures to fecal and oral microbes provide risk of disease, but are also necessary since commensal microbes play important roles in health. This work establishes that bacteria of both fecal and oral origins are commonly found on hands. It also establishes that the uniqueness of fecal and oral bacterial communities across people can allow for determination of the likely individual from whom the fecal and oral bacteria came. These techniques allow for understanding the hands as a vector for microbial transmission within families and across populations, which has important implications for public health.}, } @article {pmid29359193, year = {2018}, author = {Liu, Z and Cichocki, N and Bonk, F and Günther, S and Schattenberg, F and Harms, H and Centler, F and Müller, S}, title = {Ecological Stability Properties of Microbial Communities Assessed by Flow Cytometry.}, journal = {mSphere}, volume = {3}, number = {1}, pages = {}, doi = {10.1128/mSphere.00564-17}, pmid = {29359193}, issn = {2379-5042}, abstract = {Natural microbial communities affect human life in countless ways, ranging from global biogeochemical cycles to the treatment of wastewater and health via the human microbiome. In order to probe, monitor, and eventually control these communities, fast detection and evaluation methods are required. In order to facilitate rapid community analysis and monitor a community's dynamic behavior with high resolution, we here apply community flow cytometry, which provides single-cell-based high-dimensional data characterizing communities with high acuity over time. To interpret time series data, we draw inspiration from macroecology, in which a rich set of concepts has been developed for describing population dynamics. We focus on the stability paradigm as a promising candidate to interpret such data in an intuitive and actionable way and present a rapid workflow to monitor stability properties of complex microbial ecosystems. Based on single-cell data, we compute the stability properties resistance, resilience, displacement speed, and elasticity. For resilience, we also introduce a method which can be implemented for continuous online community monitoring. The proposed workflow was tested in a long-term continuous reactor experiment employing both an artificial and a complex microbial community, which were exposed to identical short-term disturbances. The computed stability properties uncovered the superior stability of the complex community and demonstrated the global applicability of the protocol to any microbiome. The workflow is able to support high temporal sample densities below bacterial generation times. This may provide new opportunities to unravel unknown ecological paradigms of natural microbial communities, with applications to environmental, biotechnological, and health-related microbiomes. IMPORTANCE Microbial communities drive many processes which affect human well-being directly, as in the human microbiome, or indirectly, as in natural environments or in biotechnological applications. Due to their complexity, their dynamics over time is difficult to monitor, and current sequence-based approaches are limited with respect to the temporal resolution. However, in order to eventually control microbial community dynamics, monitoring schemes of high temporal resolution are required. Flow cytometry provides single-cell-based data in the required temporal resolution, and we here use such data to compute stability properties as easy to interpret univariate indicators of microbial community dynamics. Such monitoring tools will allow for a fast, continuous, and cost-effective screening of stability states of microbiomes. Applicable to various environments, including bioreactors, surface water, and the human body, it will contribute to the development of control schemes to manipulate microbial community structures and performances.}, } @article {pmid29348922, year = {2018}, author = {Alou, MT and Ndongo, S and Frégère, L and Labas, N and Andrieu, C and Richez, M and Couderc, C and Baudoin, JP and Abrahão, J and Brah, S and Diallo, A and Sokhna, C and Cassir, N and La Scola, B and Cadoret, F and Raoult, D}, title = {Taxonogenomic description of four new Clostridium species isolated from human gut: 'Clostridium amazonitimonense', 'Clostridium merdae', 'Clostridium massilidielmoense' and 'Clostridium nigeriense'.}, journal = {New microbes and new infections}, volume = {21}, number = {}, pages = {128-139}, doi = {10.1016/j.nmni.2017.11.003}, pmid = {29348922}, issn = {2052-2975}, abstract = {Culturomics investigates microbial diversity of the human microbiome by combining diversified culture conditions, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and 16S rRNA gene identification. The present study allowed identification of four putative new Clostridium sensu stricto species: 'Clostridium amazonitimonense' strain LF2T, 'Clostridium massilidielmoense' strain MT26T, 'Clostridium nigeriense' strain Marseille-P2414T and 'Clostridium merdae' strain Marseille-P2953T, which we describe using the concept of taxonogenomics. We describe the main characteristics of each bacterium and present their complete genome sequence and annotation.}, } @article {pmid29346509, year = {2018}, author = {Zhang, J and Wei, Z and Chen, J}, title = {A distance-based approach for testing the mediation effect of the human microbiome.}, journal = {Bioinformatics (Oxford, England)}, volume = {34}, number = {11}, pages = {1875-1883}, doi = {10.1093/bioinformatics/bty014}, pmid = {29346509}, issn = {1367-4811}, abstract = {Motivation: Recent studies have revealed a complex interplay between environment, the human microbiome and health and disease. Mediation analysis of the human microbiome in these complex relationships could potentially provide insights into the role of the microbiome in the etiology of disease and, more importantly, lead to novel clinical interventions by modulating the microbiome. However, due to the high dimensionality, sparsity, non-normality and phylogenetic structure of microbiome data, none of the existing methods are suitable for testing such clinically important mediation effect.

Results: We propose a distance-based approach for testing the mediation effect of the human microbiome. In the framework, the nonlinear relationship between the human microbiome and independent/dependent variables is captured implicitly through the use of sample-wise ecological distances, and the phylogenetic tree information is conveniently incorporated by using phylogeny-based distance metrics. Multiple distance metrics are utilized to maximize the power to detect various types of mediation effect. Simulation studies demonstrate that our method has correct Type I error control, and is robust and powerful under various mediation models. Application to a real gut microbiome dataset revealed that the association between the dietary fiber intake and body mass index was mediated by the gut microbiome.

An R package 'MedTest' is freely available at https://github.com/jchen1981/MedTest.

Contact: zhiwei@njit.edu or chen.jun2@mayo.edu.

Supplementary information: Supplementary data are available at Bioinformatics online.}, } @article {pmid29341791, year = {2018}, author = {Korownyk, C and Liu, F and Garrison, S}, title = {Population level evidence for seasonality of the human microbiome.}, journal = {Chronobiology international}, volume = {35}, number = {4}, pages = {573-577}, doi = {10.1080/07420528.2018.1424718}, pmid = {29341791}, issn = {1525-6073}, abstract = {The objective of this study is to determine whether human body odors undergo seasonal modulation. We utilized google trends search volume from the United States of America from January 1, 2010 to June 24, 2017 for a number of predetermined body odors. Regression modeling of time series data was completed. Our primary outcome was to determine the proportion of the variability in Internet searches for each unpleasant odor (about the mean) that is explained by a seasonal model. We determined that the seasonal (sinusoidal) model provided a significantly better fit than the null model (best straight line fit) for all searches relating to human body odors (P <.0001 for each). This effect was easily visible to the naked eye in the raw time series data. Seasonality explained 88% of the variability in search volume for flatulence (i.e. R2 = 0.88), 65% of the variability in search volume for axillary odor, 60% of the variability in search volume for foot odor, and 58% of the variability in search volume for bad breath. Flatulence and bad breath tended to peak in January, foot odor in February, and Axillary odor in July. We conclude that searching by the general public for information on unpleasant body odors undergoes substantial seasonal variation, with the timing of peaks and troughs varying with the body part involved. The symptom burden of such smells may have a similar seasonal variation, as might the composition of the commensal bacterial microflora that play a role in creating them.}, } @article {pmid29340239, year = {2018}, author = {Tithi, SS and Aylward, FO and Jensen, RV and Zhang, L}, title = {FastViromeExplorer: a pipeline for virus and phage identification and abundance profiling in metagenomics data.}, journal = {PeerJ}, volume = {6}, number = {}, pages = {e4227}, doi = {10.7717/peerj.4227}, pmid = {29340239}, issn = {2167-8359}, abstract = {With the increase in the availability of metagenomic data generated by next generation sequencing, there is an urgent need for fast and accurate tools for identifying viruses in host-associated and environmental samples. In this paper, we developed a stand-alone pipeline called FastViromeExplorer for the detection and abundance quantification of viruses and phages in large metagenomic datasets by performing rapid searches of virus and phage sequence databases. Both simulated and real data from human microbiome and ocean environmental samples are used to validate FastViromeExplorer as a reliable tool to quickly and accurately identify viruses and their abundances in large datasets.}, } @article {pmid29340028, year = {2017}, author = {Guerrero-Preston, R and White, JR and Godoy-Vitorino, F and Rodríguez-Hilario, A and Navarro, K and González, H and Michailidi, C and Jedlicka, A and Canapp, S and Bondy, J and Dziedzic, A and Mora-Lagos, B and Rivera-Alvarez, G and Ili-Gangas, C and Brebi-Mieville, P and Westra, W and Koch, W and Kang, H and Marchionni, L and Kim, Y and Sidransky, D}, title = {High-resolution microbiome profiling uncovers Fusobacterium nucleatum, Lactobacillus gasseri/johnsonii, and Lactobacillus vaginalis associated to oral and oropharyngeal cancer in saliva from HPV positive and HPV negative patients treated with surgery and chemo-radiation.}, journal = {Oncotarget}, volume = {8}, number = {67}, pages = {110931-110948}, doi = {10.18632/oncotarget.20677}, pmid = {29340028}, issn = {1949-2553}, support = {P20 GM103475/GM/NIGMS NIH HHS/United States ; R01 CA121113/CA/NCI NIH HHS/United States ; K01 CA164092/CA/NCI NIH HHS/United States ; P50 DE019032/DE/NIDCR NIH HHS/United States ; RC2 DE020957/DE/NIDCR NIH HHS/United States ; U01 CA084986/CA/NCI NIH HHS/United States ; }, abstract = {Microbiome studies show altered microbiota in head and neck squamous cell carcinoma (HNSCC), both in terms of taxonomic composition and metabolic capacity. These studies utilized a traditional bioinformatics methodology, which allows for accurate taxonomic assignment down to the genus level, but cannot accurately resolve species level membership. We applied Resphera Insight, a high-resolution methodology for 16S rRNA taxonomic assignment that is able to provide species-level context in its assignments of 16S rRNA next generation sequencing (NGS) data. Resphera Insight applied to saliva samples from HNSCC patients and healthy controls led to the discovery that a subset of HNSCC saliva samples is significantly enriched with commensal species from the vaginal flora, including Lactobacillus gasseri/johnsonii (710x higher in saliva) and Lactobacillus vaginalis (52x higher in saliva). These species were not observed in normal saliva from Johns Hopkins patients, nor in 16S rRNA NGS saliva samples from the Human Microbiome Project (HMP). Interestingly, both species were only observed in saliva from Human Papilloma Virus (HPV) positive and HPV negative oropharyngeal cancer patients. We confirmed the representation of both species in HMP data obtained from mid-vagina (n=128) and vaginal introitus (n=121) samples. Resphera Insight also led to the discovery that Fusobacterium nucleatum, an oral cavity flora commensal bacterium linked to colon cancer, is enriched (600x higher) in saliva from a subset of HNSCC patients with advanced tumors stages. Together, these high-resolution analyses on 583 samples suggest a possible role for bacterial species in the therapeutic outcome of HPV positive and HPV negative HNSCC patients.}, } @article {pmid29332963, year = {2017}, author = {Roszyk, E and Puszczewicz, M}, title = {Role of human microbiome and selected bacterial infections in the pathogenesis of rheumatoid arthritis.}, journal = {Reumatologia}, volume = {55}, number = {5}, pages = {242-250}, doi = {10.5114/reum.2017.71641}, pmid = {29332963}, issn = {0034-6233}, abstract = {Microorganisms inhabiting human body form a complex ecosystem. The mutual influence of the microbiome and the immune system of the host constitute the basis for numerous diseases, e.g. pseudomembranous colitis, inflammatory bowel disease, type 1 diabetes, atopic diseases, obesity, reactive arthritis. New molecular diagnostic methods and multi-center studies may help in understanding of the role of microbiota in health and disease. Rheumatoid arthritis has a multi-faceted etiology, and its causes are not entirely understood. There are indications for the influence of microbiomes of oral cavity, intestines, lungs and urinary tract on the development of rheumatoid arthritis. Interactions between microorganisms and human immune system play role in the pathogenesis of the disease.}, } @article {pmid29330190, year = {2018}, author = {Kraemer, JG and Ramette, A and Aebi, S and Oppliger, A and Hilty, M}, title = {Influence of pig farming on the human's nasal microbiota: The key role of the airborne microbial communities.}, journal = {Applied and environmental microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1128/AEM.02470-17}, pmid = {29330190}, issn = {1098-5336}, abstract = {It has been hypothesized that the environment can influence the composition of the nasal microbiota. However, the direct influence of pig farming on the anterior and posterior nasal microbiota is unknown. Using a cross-sectional design, pig farms (n=28) were visited in 2014-2015 and nasal swabs from 43 pig farmers and 56 pigs as well as 27 air samples taken in the vicinity of pig enclosure were collected. As controls, nasal swabs from 17 cow farmers and 26 non-animal exposed individuals were also included. Analyses of the microbiota were performed based on 16S rRNA amplicon sequencing and the DADA2 pipeline to define sequence variants (SVs). We found that pig farming is strongly associated with specific microbial signatures (including alpha- and beta-diversity), which are reflected in the microbiota of the human nose. Furthermore, the microbial communities were more similar within the same farm as compared to between the different farms, indicating a specific microbiota pattern for each pig farm. In total, there were 82 SVs that occurred significantly more abundantly in samples from pig farms than from cow farmers and non-exposed (i.e. the core pig farm microbiota). Of those, nine SVs were significantly associated with the posterior part of the humans' nose. The results strongly indicate that pig farming is associated with a distinct human nose microbiota. Finally, the community structures derived by the DADA2 pipeline showed an excellent agreement with the outputs of the mothur pipeline which was revealed by procrustes analyses.Importance The knowledge about the influence of animal keeping on the human microbiome is important. Previous research shows that pets are significantly affecting the microbial communities of humans. However, the effect of animal farming on the human microbiome is less clear although it is known that the air in farms, and in particular pig farms, is charged with high amounts of dust, bacteria and fungi. In this study we have simultaneously investigated the nasal microbiota of pigs, humans and the environment in pig farms. We reveal an enormous impact of pig farming on the human nasal microbiota which is far more pronounced as compared to cow farming. In addition, we have analyzed the airborne microbiota and found significant associations suggesting an animal-human transmission of the microbiota within pig farms. We also reveal that microbial patterns are farm-specific suggesting that the environment influences animals and humans in a similar manner.}, } @article {pmid29325418, year = {2018}, author = {Balskus, EP}, title = {The Human Microbiome.}, journal = {ACS infectious diseases}, volume = {4}, number = {1}, pages = {1-2}, doi = {10.1021/acsinfecdis.7b00248}, pmid = {29325418}, issn = {2373-8227}, } @article {pmid29321635, year = {2018}, author = {Brüggemann, H and Jensen, A and Nazipi, S and Aslan, H and Meyer, RL and Poehlein, A and Brzuszkiewicz, E and Al-Zeer, MA and Brinkmann, V and Söderquist, B}, title = {Pan-genome analysis of the genus Finegoldia identifies two distinct clades, strain-specific heterogeneity, and putative virulence factors.}, journal = {Scientific reports}, volume = {8}, number = {1}, pages = {266}, doi = {10.1038/s41598-017-18661-8}, pmid = {29321635}, issn = {2045-2322}, abstract = {Finegoldia magna, a Gram-positive anaerobic coccus, is an opportunistic pathogen, associated with medical device-related infections. F. magna is the only described species of the genus Finegoldia. We report the analysis of 17 genomes of Finegoldia isolates. Phylogenomic analyses showed that the Finegoldia population can be divided into two distinct clades, with an average nucleotide identity of 90.7%. One clade contains strains of F. magna, whereas the other clade includes more heterogeneous strains, hereafter tentatively named "Finegoldia nericia". The latter species appears to be more abundant in the human microbiome. Surface structure differences between strains of F. magna and "F. nericia" were detected by microscopy. Strain-specific heterogeneity is high and previously identified host-interacting factors are present only in subsets of "F. nericia" and F. magna strains. However, all genomes encode multiple host factor-binding proteins such as albumin-, collagen-, and immunoglobulin-binding proteins, and two to four copies of CAMP (Christie-Atkins-Munch-Petersen) factors; in accordance, most strains show a positive CAMP reaction for co-hemolysis. Our work sheds new light of the genus Finegoldia and its ability to bind host components. Future research should explore if the genomic differences identified here affect the potential of different Finegoldia species and strains to cause opportunistic infections.}, } @article {pmid29321519, year = {2018}, author = {Stokholm, J and Blaser, MJ and Thorsen, J and Rasmussen, MA and Waage, J and Vinding, RK and Schoos, AM and Kunøe, A and Fink, NR and Chawes, BL and Bønnelykke, K and Brejnrod, AD and Mortensen, MS and Al-Soud, WA and Sørensen, SJ and Bisgaard, H}, title = {Maturation of the gut microbiome and risk of asthma in childhood.}, journal = {Nature communications}, volume = {9}, number = {1}, pages = {141}, doi = {10.1038/s41467-017-02573-2}, pmid = {29321519}, issn = {2041-1723}, support = {R01 DK090989/DK/NIDDK NIH HHS/United States ; }, abstract = {The composition of the human gut microbiome matures within the first years of life. It has been hypothesized that microbial compositions in this period can cause immune dysregulations and potentially cause asthma. Here we show, by associating gut microbial composition from 16S rRNA gene amplicon sequencing during the first year of life with subsequent risk of asthma in 690 participants, that 1-year-old children with an immature microbial composition have an increased risk of asthma at age 5 years. This association is only apparent among children born to asthmatic mothers, suggesting that lacking microbial stimulation during the first year of life can trigger their inherited asthma risk. Conversely, adequate maturation of the gut microbiome in this period may protect these pre-disposed children.}, } @article {pmid29311644, year = {2018}, author = {Schirmer, M and Franzosa, EA and Lloyd-Price, J and McIver, LJ and Schwager, R and Poon, TW and Ananthakrishnan, AN and Andrews, E and Barron, G and Lake, K and Prasad, M and Sauk, J and Stevens, B and Wilson, RG and Braun, J and Denson, LA and Kugathasan, S and McGovern, DPB and Vlamakis, H and Xavier, RJ and Huttenhower, C}, title = {Dynamics of metatranscription in the inflammatory bowel disease gut microbiome.}, journal = {Nature microbiology}, volume = {3}, number = {3}, pages = {337-346}, doi = {10.1038/s41564-017-0089-z}, pmid = {29311644}, issn = {2058-5276}, support = {U54 DK102557/DK/NIDDK NIH HHS/United States ; U01 DK062413/DK/NIDDK NIH HHS/United States ; P30 DK043351/DK/NIDDK NIH HHS/United States ; R01 DK092405/DK/NIDDK NIH HHS/United States ; P01 DK046763/DK/NIDDK NIH HHS/United States ; UL1 TR001881/TR/NCATS NIH HHS/United States ; }, abstract = {Inflammatory bowel disease (IBD) is a group of chronic diseases of the digestive tract that affects millions of people worldwide. Genetic, environmental and microbial factors have been implicated in the onset and exacerbation of IBD. However, the mechanisms associating gut microbial dysbioses and aberrant immune responses remain largely unknown. The integrative Human Microbiome Project seeks to close these gaps by examining the dynamics of microbiome functionality in disease by profiling the gut microbiomes of >100 individuals sampled over a 1-year period. Here, we present the first results based on 78 paired faecal metagenomes and metatranscriptomes, and 222 additional metagenomes from 59 patients with Crohn's disease, 34 with ulcerative colitis and 24 non-IBD control patients. We demonstrate several cases in which measures of microbial gene expression in the inflamed gut can be informative relative to metagenomic profiles of functional potential. First, although many microbial organisms exhibited concordant DNA and RNA abundances, we also detected species-specific biases in transcriptional activity, revealing predominant transcription of pathways by individual microorganisms per host (for example, by Faecalibacterium prausnitzii). Thus, a loss of these organisms in disease may have more far-reaching consequences than suggested by their genomic abundances. Furthermore, we identified organisms that were metagenomically abundant but inactive or dormant in the gut with little or no expression (for example, Dialister invisus). Last, certain disease-specific microbial characteristics were more pronounced or only detectable at the transcript level, such as pathways that were predominantly expressed by different organisms in patients with IBD (for example, Bacteroides vulgatus and Alistipes putredinis). This provides potential insights into gut microbial pathway transcription that can vary over time, inducing phenotypical changes that are complementary to those linked to metagenomic abundances. The study's results highlight the strength of analysing both the activity and the presence of gut microorganisms to provide insight into the role of the microbiome in IBD.}, } @article {pmid29311119, year = {2018}, author = {Clemente, JC and Manasson, J and Scher, JU}, title = {The role of the gut microbiome in systemic inflammatory disease.}, journal = {BMJ (Clinical research ed.)}, volume = {360}, number = {}, pages = {j5145}, pmid = {29311119}, issn = {1756-1833}, support = {S10 OD018522/OD/NIH HHS/United States ; T32 AR069515/AR/NIAMS NIH HHS/United States ; K23 AR064318/AR/NIAMS NIH HHS/United States ; R03 AR072182/AR/NIAMS NIH HHS/United States ; }, mesh = {Autoimmune Diseases/immunology/*microbiology ; Fecal Microbiota Transplantation/methods ; Feeding Behavior/*physiology ; Gastrointestinal Microbiome/*immunology/physiology ; Humans ; Inflammation/immunology/*microbiology ; Inflammatory Bowel Diseases/immunology/*microbiology/pathology ; Microbiota ; Mucous Membrane/immunology/*microbiology ; Prebiotics ; Probiotics ; }, abstract = {The role of the gut microbiome in models of inflammatory and autoimmune disease is now well characterized. Renewed interest in the human microbiome and its metabolites, as well as notable advances in host mucosal immunology, has opened multiple avenues of research to potentially modulate inflammatory responses. The complexity and interdependence of these diet-microbe-metabolite-host interactions are rapidly being unraveled. Importantly, most of the progress in the field comes from new knowledge about the functional properties of these microorganisms in physiology and their effect in mucosal immunity and distal inflammation. This review summarizes the preclinical and clinical evidence on how dietary, probiotic, prebiotic, and microbiome based therapeutics affect our understanding of wellness and disease, particularly in autoimmunity.}, } @article {pmid29282061, year = {2017}, author = {Davenport, ER and Sanders, JG and Song, SJ and Amato, KR and Clark, AG and Knight, R}, title = {The human microbiome in evolution.}, journal = {BMC biology}, volume = {15}, number = {1}, pages = {127}, doi = {10.1186/s12915-017-0454-7}, pmid = {29282061}, issn = {1741-7007}, support = {F32 DK109595/DK/NIDDK NIH HHS/United States ; }, abstract = {The trillions of microbes living in the gut-the gut microbiota-play an important role in human biology and disease. While much has been done to explore its diversity, a full understanding of our microbiomes demands an evolutionary perspective. In this review, we compare microbiomes from human populations, placing them in the context of microbes from humanity's near and distant animal relatives. We discuss potential mechanisms to generate host-specific microbiome configurations and the consequences of disrupting those configurations. Finally, we propose that this broader phylogenetic perspective is useful for understanding the mechanisms underlying human-microbiome interactions.}, } @article {pmid29281638, year = {2017}, author = {Lo, C and Marculescu, R}, title = {MPLasso: Inferring microbial association networks using prior microbial knowledge.}, journal = {PLoS computational biology}, volume = {13}, number = {12}, pages = {e1005915}, doi = {10.1371/journal.pcbi.1005915}, pmid = {29281638}, issn = {1553-7358}, mesh = {Algorithms ; Computational Biology ; Data Mining ; Databases, Genetic ; Humans ; Machine Learning ; Microbial Consortia/genetics/*physiology ; Microbial Interactions/*physiology ; Microbiota/genetics/*physiology ; Models, Biological ; }, abstract = {Due to the recent advances in high-throughput sequencing technologies, it becomes possible to directly analyze microbial communities in human body and environment. To understand how microbial communities adapt, develop, and interact with the human body and the surrounding environment, one of the fundamental challenges is to infer the interactions among different microbes. However, due to the compositional and high-dimensional nature of microbial data, statistical inference cannot offer reliable results. Consequently, new approaches that can accurately and robustly estimate the associations (putative interactions) among microbes are needed to analyze such compositional and high-dimensional data. We propose a novel framework called Microbial Prior Lasso (MPLasso) which integrates graph learning algorithm with microbial co-occurrences and associations obtained from scientific literature by using automated text mining. We show that MPLasso outperforms existing models in terms of accuracy, microbial network recovery rate, and reproducibility. Furthermore, the association networks we obtain from the Human Microbiome Project datasets show credible results when compared against laboratory data.}, } @article {pmid29277868, year = {2018}, author = {Maltez Thomas, A and Prata Lima, F and Maria Silva Moura, L and Maria da Silva, A and Dias-Neto, E and Setubal, JC}, title = {Comparative Metagenomics.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {1704}, number = {}, pages = {243-260}, doi = {10.1007/978-1-4939-7463-4_8}, pmid = {29277868}, issn = {1940-6029}, abstract = {Thanks in large part to newer, better, and cheaper DNA sequencing technologies, an enormous number of metagenomic sequence datasets have been and continue to be generated, covering a huge variety of environmental niches, including several different human body sites. Comparing these metagenomes and identifying their commonalities and differences is a challenging task, due not only to the large amounts of data, but also because there are several methodological considerations that need to be taken into account to ensure an appropriate and sound comparison between datasets. In this chapter, we describe current techniques aimed at comparing metagenomes generated by 16S ribosomal RNA and shotgun DNA sequencing, emphasizing methodological issues that arise in these comparative studies. We provide a detailed case study to illustrate some of these techniques using data from the Human Microbiome Project comparing the microbial communities from ten buccal mucosa samples with ten tongue dorsum samples in terms of alpha diversity, beta diversity, and their taxonomic and functional profiles.}, } @article {pmid29276775, year = {2018}, author = {Van Dyke, TE and Diaz, PI and Moutsopoulos, N and Alekseyenko, AV and Ioannidou, E}, title = {Task Force on Design and Analysis in Oral Health Research: Host-Microbiome Interactions in Dysbiosis.}, journal = {JDR clinical and translational research}, volume = {3}, number = {1}, pages = {6-9}, doi = {10.1177/2380084417728488}, pmid = {29276775}, issn = {2380-0844}, support = {R21 AR067459/AR/NIAMS NIH HHS/United States ; R01 DE025383/DE/NIDCR NIH HHS/United States ; R21 DE023967/DE/NIDCR NIH HHS/United States ; R01 DE021578/DE/NIDCR NIH HHS/United States ; R01 DE025020/DE/NIDCR NIH HHS/United States ; }, abstract = {Knowledge Transfer Statement: This article discusses the proceedings of the conference organized by the Task Force on Design and Analysis in Oral Health Research on the new advances in host-microbiome interactions, analytical methods, and their implication in inflammatory periodontal disease management.}, } @article {pmid29269494, year = {2018}, author = {Collins, SL and McMillan, A and Seney, S and van der Veer, C and Kort, R and Sumarah, MW and Reid, G}, title = {Promising Prebiotic Candidate Established by Evaluation of Lactitol, Lactulose, Raffinose, and Oligofructose for Maintenance of a Lactobacillus-Dominated Vaginal Microbiota.}, journal = {Applied and environmental microbiology}, volume = {84}, number = {5}, pages = {}, doi = {10.1128/AEM.02200-17}, pmid = {29269494}, issn = {1098-5336}, abstract = {Perturbations to the vaginal microbiota can lead to dysbiosis, including bacterial vaginosis (BV), which affects a large portion of the female population. In a healthy state, the vaginal microbiota is characterized by low diversity and colonization by Lactobacillus spp., whereas in BV, these species are displaced by a highly diverse population of bacteria associated with adverse vaginal health outcomes. Since prebiotic ingestion has been a highly effective approach to invigorate lactobacilli for improved intestinal health, we hypothesized that these compounds could stimulate lactobacilli at the expense of BV organisms to maintain vaginal health. Monocultures of commensal Lactobacillus crispatus, Lactobacillus vaginalis, Lactobacillus gasseri, Lactobacillus johnsonii, Lactobacillus jensenii, and Lactobacillus iners, in addition to BV-associated organisms and Candida albicans, were tested for their ability to utilize a representative group of prebiotics consisting of lactitol, lactulose, raffinose, and oligofructose. The disaccharide lactulose was found to most broadly and specifically stimulate vaginal lactobacilli, including the strongly health-associated species L. crispatus, and importantly, not to stimulate BV organisms or C. albicans Using freshly collected vaginal samples, we showed that exposure to lactulose promoted commensal Lactobacillus growth and dominance and resulted in healthy acidity partially through lactic acid production. This provides support for further testing of lactulose to prevent dysbiosis and potentially to reduce the need for antimicrobial agents in managing vaginal health.IMPORTANCE Bacterial vaginosis (BV) and other dysbioses of the vaginal microbiota significantly affect the quality of life of millions of women. Antimicrobial therapy is often poorly effective, causes side effects, and does not prevent recurrences. We report one of very few studies that have evaluated how prebiotics-compounds that are selectively fermented by beneficial bacteria such as Lactobacillus spp.-can modulate the vaginal microbiota. We also report use of a novel in vitro polymicrobial model to study the impact of prebiotics on the vaginal microbiota. The identification of prebiotic lactulose as enhancing Lactobacillus growth but not that of BV organisms or Candida albicans has direct application for retention of homeostasis and prevention of vaginal dysbiosis and infection.}, } @article {pmid29262868, year = {2017}, author = {Fenn, K and Strandwitz, P and Stewart, EJ and Dimise, E and Rubin, S and Gurubacharya, S and Clardy, J and Lewis, K}, title = {Quinones are growth factors for the human gut microbiota.}, journal = {Microbiome}, volume = {5}, number = {1}, pages = {161}, doi = {10.1186/s40168-017-0380-5}, pmid = {29262868}, issn = {2049-2618}, support = {R01 AT009874/AT/NCCIH NIH HHS/United States ; R01HG005824//National Institutes of Health/ ; R01GM086158//National Institutes of Health/ ; }, mesh = {Actinobacteria/drug effects/growth & development ; Bacteria/*drug effects/*growth & development ; Bacterial Physiological Phenomena/drug effects ; Bacteriological Techniques ; Coculture Techniques ; Escherichia coli/drug effects/growth & development ; Faecalibacterium/drug effects/growth & development ; Feces/microbiology ; Gastrointestinal Microbiome/*drug effects ; Humans ; Intercellular Signaling Peptides and Proteins/genetics/*pharmacology ; Phylogeny ; Siderophores/metabolism ; Ubiquinone/metabolism ; Vitamin K 2/*metabolism/pharmacology ; }, abstract = {BACKGROUND: The human gut microbiome has been linked to numerous components of health and disease. However, approximately 25% of the bacterial species in the gut remain uncultured, which limits our ability to properly understand, and exploit, the human microbiome. Previously, we found that growing environmental bacteria in situ in a diffusion chamber enables growth of uncultured species, suggesting the existence of growth factors in the natural environment not found in traditional cultivation media. One source of growth factors proved to be neighboring bacteria, and by using co-culture, we isolated previously uncultured organisms from the marine environment and identified siderophores as a major class of bacterial growth factors. Here, we employ similar co-culture techniques to grow bacteria from the human gut microbiome and identify novel growth factors.

RESULTS: By testing dependence of slow-growing colonies on faster-growing neighboring bacteria in a co-culture assay, eight taxonomically diverse pairs of bacteria were identified, in which an "induced" isolate formed a gradient of growth around a cultivatable "helper." This set included two novel species Faecalibacterium sp. KLE1255-belonging to the anti-inflammatory Faecalibacterium genus-and Sutterella sp. KLE1607. While multiple helper strains were identified, Escherichia coli was also capable of promoting growth of all induced isolates. Screening a knockout library of E. coli showed that a menaquinone biosynthesis pathway was required for growth induction of Faecalibacterium sp. KLE1255 and other induced isolates. Purified menaquinones induced growth of 7/8 of the isolated strains, quinone specificity profiles for individual bacteria were identified, and genome analysis suggests an incomplete menaquinone biosynthetic capability yet the presence of anaerobic terminal reductases in the induced strains, indicating an ability to respire anaerobically.

CONCLUSIONS: Our data show that menaquinones are a major class of growth factors for bacteria from the human gut microbiome. These organisms are taxonomically diverse, including members of the genus Faecalibacterium, Bacteroides, Bilophila, Gordonibacter, and Sutterella. This suggests that loss of quinone biosynthesis happened independently in many lineages of the human microbiota. Quinones can be used to improve existing bacterial growth media or modulate the human gut microbiota by encouraging the growth of important symbionts, such as Faecalibacterium species.}, } @article {pmid29257783, year = {2018}, author = {Akrami, K and Sweeney, DA}, title = {The microbiome of the critically ill patient.}, journal = {Current opinion in critical care}, volume = {24}, number = {1}, pages = {49-54}, doi = {10.1097/MCC.0000000000000469}, pmid = {29257783}, issn = {1531-7072}, mesh = {Clostridium Infections/microbiology/therapy ; Colitis, Ulcerative/microbiology/therapy ; *Critical Illness/therapy ; Dysbiosis/etiology/*microbiology/therapy ; Fecal Microbiota Transplantation ; Humans ; Intensive Care Units ; Microbiota/*physiology ; Pneumonia, Ventilator-Associated/microbiology/therapy ; Probiotics/therapeutic use ; Treatment Outcome ; }, abstract = {PURPOSE OF REVIEW: Advances in the understanding of the human microbiome outside of the ICU have led investigators to consider the role of the microbiome in critical illness. The picture that is being elucidated is one of dysbiosis occurring at multiple sites in the critically ill patient. This review describes the changes that occur in the various microbiomes of a critically ill patient, the implications of these changes and shows how advances in the understanding of dysbiosis may lead to microbiome-targeted therapies.

RECENT FINDINGS: Critically ill patients undergo dysbiosis at several organ sites including the skin, gastrointestinal system and the lungs with loss of microbial diversity and a propensity for potentially pathogenic organisms to dominate a particular microbiome. These microbiome changes appear to be predictive of clinical outcome. While the use of fecal microbial transplantation has been demonstrated to be an effective treatment for recurrent Clostridium difficile infection, the use of fecal microbial transplantation and other microbiome modifying therapies may have a role in managing critical illness in the ICU.

SUMMARY: A growing understanding of the microbiome in the critically ill may modify current dogma regarding the pathogenesis of sepsis and other life-threatening conditions seen in the ICU, thereby fundamentally changing antibiotic stewardship and the management of the critically ill patient.}, } @article {pmid29253074, year = {2018}, author = {Huang, L and Krüger, J and Sczyrba, A}, title = {Analyzing large scale genomic data on the cloud with Sparkhit.}, journal = {Bioinformatics (Oxford, England)}, volume = {34}, number = {9}, pages = {1457-1465}, doi = {10.1093/bioinformatics/btx808}, pmid = {29253074}, issn = {1367-4811}, abstract = {Motivation: The increasing amount of next-generation sequencing data poses a fundamental challenge on large scale genomic analytics. Existing tools use different distributed computational platforms to scale-out bioinformatics workloads. However, the scalability of these tools is not efficient. Moreover, they have heavy run time overheads when pre-processing large amounts of data. To address these limitations, we have developed Sparkhit: a distributed bioinformatics framework built on top of the Apache Spark platform.

Results: Sparkhit integrates a variety of analytical methods. It is implemented in the Spark extended MapReduce model. It runs 92-157 times faster than MetaSpark on metagenomic fragment recruitment and 18-32 times faster than Crossbow on data pre-processing. We analyzed 100 terabytes of data across four genomic projects in the cloud in 21 h, which includes the run times of cluster deployment and data downloading. Furthermore, our application on the entire Human Microbiome Project shotgun sequencing data was completed in 2 h, presenting an approach to easily associate large amounts of public datasets with reference data.

Sparkhit is freely available at: https://rhinempi.github.io/sparkhit/.

Contact: asczyrba@cebitec.uni-bielefeld.de.

Supplementary information: Supplementary data are available at Bioinformatics online.}, } @article {pmid29242834, year = {2017}, author = {Usyk, M and Zolnik, CP and Patel, H and Levi, MH and Burk, RD}, title = {Novel ITS1 Fungal Primers for Characterization of the Mycobiome.}, journal = {mSphere}, volume = {2}, number = {6}, pages = {}, doi = {10.1128/mSphere.00488-17}, pmid = {29242834}, issn = {2379-5042}, support = {P30 DK041296/DK/NIDDK NIH HHS/United States ; P30 AI051519/AI/NIAID NIH HHS/United States ; R56 AI072204/AI/NIAID NIH HHS/United States ; K12 GM102779/GM/NIGMS NIH HHS/United States ; R01 CA078527/CA/NCI NIH HHS/United States ; R01 AI072204/AI/NIAID NIH HHS/United States ; U01 CA078527/CA/NCI NIH HHS/United States ; P30 CA013330/CA/NCI NIH HHS/United States ; }, abstract = {Studies of the human microbiome frequently omit characterization of fungal communities (the mycobiome), which limits our ability to investigate how fungal communities influence human health. The internal transcribed spacer 1 (ITS1) region of the eukaryotic ribosomal cluster has features allowing for wide taxonomic coverage and has been recognized as a suitable barcode region for species-level identification of fungal organisms. We developed custom ITS1 primer sets using iterative alignment refinement. Primer performance was evaluated using in silico testing and experimental testing of fungal cultures and human samples. Using an expanded novel reference database, SIS (18S-ITS1-5.8S), the newly designed primers showed an average in silico taxonomic coverage of 79.9% ± 7.1% compared to a coverage of 44.6% ± 13.2% using previously published primers (P = 0.05). The newly described primer sets recovered an average of 21,830 ± 225 fungal reads from fungal isolate culture samples, whereas the previously published primers had an average of 3,305 ± 1,621 reads (P = 0.03). Of note was an increase in the taxonomic coverage of the Candida genus, which went from a mean coverage of 59.5% ± 13% to 100.0% ± 0.0% (P = 0.0015) comparing the previously described primers to the new primers, respectively. The newly developed ITS1 primer sets significantly improve general taxonomic coverage of fungal communities infecting humans and increased read depth by an order of magnitude over the best-performing published primer set tested. The overall best-performing primer pair in terms of taxonomic coverage and read recovery, ITS1-30F/ITS1-217R, will aid in advancing research in the area of the human mycobiome. IMPORTANCE The mycobiome constitutes all the fungal organisms within an environment or biological niche. The fungi are eukaryotes, are extremely heterogeneous, and include yeasts and molds that colonize humans as part of the microbiome. In addition, fungi can also infect humans and cause disease. Characterization of the bacterial component of the microbiome was revolutionized by 16S rRNA gene fragment amplification, next-generation sequencing technologies, and bioinformatics pipelines. Characterization of the mycobiome has often not been included in microbiome studies because of limitations in amplification systems. This report revisited the selection of PCR primers that amplify the fungal ITS1 region. We have identified primers with superior identification of fungi present in the database. We have compared the new primer sets against those previously used in the literature and show a significant improvement in read count and taxon identification. These primers should facilitate the study of fungi in human physiology and disease states.}, } @article {pmid29232932, year = {2017}, author = {Vitetta, L and Saltzman, ET and Thomsen, M and Nikov, T and Hall, S}, title = {Adjuvant Probiotics and the Intestinal Microbiome: Enhancing Vaccines and Immunotherapy Outcomes.}, journal = {Vaccines}, volume = {5}, number = {4}, pages = {}, doi = {10.3390/vaccines5040050}, pmid = {29232932}, issn = {2076-393X}, abstract = {Immune defence against pathogenic agents comprises the basic premise for the administration of vaccines. Vaccinations have hence prevented millions of infectious illnesses, hospitalizations and mortality. Acquired immunity comprises antibody and cell mediated responses and is characterized by its specificity and memory. Along a similar congruent yet diverse mode of disease prevention, the human host has negotiated from in utero and at birth with the intestinal commensal bacterial cohort to maintain local homeostasis in order to achieve immunological tolerance in the new born. The advent of the Human Microbiome Project has redefined an appreciation of the interactions between the host and bacteria in the intestines from one of a collection of toxic waste to one of a symbiotic existence. Probiotics comprise bacterial genera thought to provide a health benefit to the host. The intestinal microbiota has profound effects on local and extra-intestinal end organ physiology. As such, we further posit that the adjuvant administration of dedicated probiotic formulations can encourage the intestinal commensal cohort to beneficially participate in the intestinal microbiome-intestinal epithelia-innate-cell mediated immunity axes and cell mediated cellular immunity with vaccines aimed at preventing infectious diseases whilst conserving immunological tolerance. The strength of evidence for the positive effect of probiotic administration on acquired immune responses has come from various studies with viral and bacterial vaccines. We posit that the introduction early of probiotics may provide significant beneficial immune outcomes in neonates prior to commencing a vaccination schedule or in elderly adults prior to the administration of vaccinations against influenza viruses.}, } @article {pmid29232848, year = {2017}, author = {Vernocchi, P and Del Chierico, F and Quagliariello, A and Ercolini, D and Lucidi, V and Putignani, L}, title = {A Metagenomic and in Silico Functional Prediction of Gut Microbiota Profiles May Concur in Discovering New Cystic Fibrosis Patient-Targeted Probiotics.}, journal = {Nutrients}, volume = {9}, number = {12}, pages = {}, doi = {10.3390/nu9121342}, pmid = {29232848}, issn = {2072-6643}, mesh = {Bacteria/*genetics ; Case-Control Studies ; Child, Preschool ; Cystic Fibrosis/*microbiology ; Feces/microbiology ; Female ; *Gastrointestinal Microbiome ; Humans ; Male ; Metagenomics/*methods ; Phylogeny ; *Probiotics ; RNA, Ribosomal, 16S/analysis ; }, abstract = {Cystic fibrosis (CF) is a life-limiting hereditary disorder that results in aberrant mucosa in the lungs and digestive tract, chronic respiratory infections, chronic inflammation, and the need for repeated antibiotic treatments. Probiotics have been demonstrated to improve the quality of life of CF patients. We investigated the distribution of gut microbiota (GM) bacteria to identify new potential probiotics for CF patients on the basis of GM patterns. Fecal samples of 28 CF patients and 31 healthy controls (HC) were collected and analyzed by 16S rRNA-based pyrosequencing analysis of GM, to produce CF-HC paired maps of the distribution of operational taxonomic units (OTUs), and by Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) for Kyoto Encyclopedia of Genes and Genomes (KEGG) biomarker prediction. The maps were scanned to highlight the distribution of bacteria commonly claimed as probiotics, such as bifidobacteria and lactobacilli, and of butyrate-producing colon bacteria, such as Eubacterium spp. and Faecalibacterium prausnitzii. The analyses highlighted 24 OTUs eligible as putative probiotics. Eleven and nine species were prevalently associated with the GM of CF and HC subjects, respectively. Their KEGG prediction provided differential CF and HC pathways, indeed associated with health-promoting biochemical activities in the latter case. GM profiling and KEGG biomarkers concurred in the evaluation of nine bacterial species as novel putative probiotics that could be investigated for the nutritional management of CF patients.}, } @article {pmid29227922, year = {2018}, author = {Gao, W and Howden, BP and Stinear, TP}, title = {Evolution of virulence in Enterococcus faecium, a hospital-adapted opportunistic pathogen.}, journal = {Current opinion in microbiology}, volume = {41}, number = {}, pages = {76-82}, doi = {10.1016/j.mib.2017.11.030}, pmid = {29227922}, issn = {1879-0364}, abstract = {Enterococci are long-standing members of the human microbiome and they are also widely distributed in nature. However, with the surge of antibiotic-resistance in recent decades, two enterococcal species (Enterococcus faecalis and Enterococcus faecium) have emerged to become significant nosocomial pathogens, acquiring extensive antibiotic resistance. In this review, we summarize what is known about the evolution of virulence in E. faecium, highlighting a specific clone of E. faecium called ST796 that has emerged recently and spread globally.}, } @article {pmid29227468, year = {2018}, author = {Beaulaurier, J and Zhu, S and Deikus, G and Mogno, I and Zhang, XS and Davis-Richardson, A and Canepa, R and Triplett, EW and Faith, JJ and Sebra, R and Schadt, EE and Fang, G}, title = {Metagenomic binning and association of plasmids with bacterial host genomes using DNA methylation.}, journal = {Nature biotechnology}, volume = {36}, number = {1}, pages = {61-69}, doi = {10.1038/nbt.4037}, pmid = {29227468}, issn = {1546-1696}, support = {R01 GM114472/GM/NIGMS NIH HHS/United States ; }, abstract = {Shotgun metagenomics methods enable characterization of microbial communities in human microbiome and environmental samples. Assembly of metagenome sequences does not output whole genomes, so computational binning methods have been developed to cluster sequences into genome 'bins'. These methods exploit sequence composition, species abundance, or chromosome organization but cannot fully distinguish closely related species and strains. We present a binning method that incorporates bacterial DNA methylation signatures, which are detected using single-molecule real-time sequencing. Our method takes advantage of these endogenous epigenetic barcodes to resolve individual reads and assembled contigs into species- and strain-level bins. We validate our method using synthetic and real microbiome sequences. In addition to genome binning, we show that our method links plasmids and other mobile genetic elements to their host species in a real microbiome sample. Incorporation of DNA methylation information into shotgun metagenomics analyses will complement existing methods to enable more accurate sequence binning.}, } @article {pmid29221589, year = {2017}, author = {Lebaron, P and Bourrain, M}, title = {.}, journal = {Annales de dermatologie et de venereologie}, volume = {144 Suppl 1}, number = {}, pages = {S35-S41}, doi = {10.1016/S0151-9638(17)31041-4}, pmid = {29221589}, issn = {0151-9638}, abstract = {Human hosts a large number of microorganisms that constitute its microbiome and the vast majority of them are very useful and even essentials. The human microbiome is a complex ecosystem where live populations of transient or resident microorganisms. The process of co-development or co-adaptation played a major role in the establishment of indigenous communities and help explain the dominance of positive interactions (commensal, symbiotic or mutualistic) in the human-microorganism relationship. The assimilation of nutrients, production of anti-inflammatory compounds, defense against pathogens, vitamin production or stimulating the immune system are some of the key benefits of the indigenous microorganisms. Understanding the skin microbiome opens new exploratory fields and represents a real challenge for both the academic knowledge and the development of new therapeutic approaches.}, } @article {pmid29211710, year = {2017}, author = {Surana, NK and Kasper, DL}, title = {Moving beyond microbiome-wide associations to causal microbe identification.}, journal = {Nature}, volume = {552}, number = {7684}, pages = {244-247}, doi = {10.1038/nature25019}, pmid = {29211710}, issn = {1476-4687}, support = {K08 AI108690/AI/NIAID NIH HHS/United States ; U19 AI109764/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Body Weight ; Cell Survival ; Clostridium/genetics/*isolation & purification/*physiology ; Colitis/*microbiology/*prevention & control ; Feces/microbiology ; *Gastrointestinal Microbiome/genetics ; Germ-Free Life ; Intestines/metabolism/microbiology ; Lactobacillus reuteri/genetics/physiology ; Mice ; Pancreatitis-Associated Proteins/metabolism ; *Phenotype ; Ruminococcus/genetics/physiology ; Symbiosis ; }, abstract = {Microbiome-wide association studies have established that numerous diseases are associated with changes in the microbiota. These studies typically generate a long list of commensals implicated as biomarkers of disease, with no clear relevance to disease pathogenesis. If the field is to move beyond correlations and begin to address causation, an effective system is needed for refining this catalogue of differentially abundant microbes and to allow subsequent mechanistic studies. Here we demonstrate that triangulation of microbe-phenotype relationships is an effective method for reducing the noise inherent in microbiota studies and enabling identification of causal microbes. We found that gnotobiotic mice harbouring different microbial communities exhibited differential survival in a colitis model. Co-housing of these mice generated animals that had hybrid microbiotas and displayed intermediate susceptibility to colitis. Mapping of microbe-phenotype relationships in parental mouse strains and in mice with hybrid microbiotas identified the bacterial family Lachnospiraceae as a correlate for protection from disease. Using directed microbial culture techniques, we discovered Clostridium immunis, a previously unknown bacterial species from this family, that-when administered to colitis-prone mice-protected them against colitis-associated death. To demonstrate the generalizability of our approach, we used it to identify several commensal organisms that induce intestinal expression of an antimicrobial peptide. Thus, we have used microbe-phenotype triangulation to move beyond the standard correlative microbiome study and identify causal microbes for two completely distinct phenotypes. Identification of disease-modulating commensals by microbe-phenotype triangulation may be more broadly applicable to human microbiome studies.}, } @article {pmid29209090, year = {2017}, author = {Duvallet, C and Gibbons, SM and Gurry, T and Irizarry, RA and Alm, EJ}, title = {Meta-analysis of gut microbiome studies identifies disease-specific and shared responses.}, journal = {Nature communications}, volume = {8}, number = {1}, pages = {1784}, doi = {10.1038/s41467-017-01973-8}, pmid = {29209090}, issn = {2041-1723}, support = {P30 DK043351/DK/NIDDK NIH HHS/United States ; }, mesh = {Bacteria/classification/*growth & development ; Case-Control Studies ; Feces/microbiology ; Gastrointestinal Diseases/*microbiology ; *Gastrointestinal Microbiome ; Gastrointestinal Tract/*microbiology ; Humans ; Population Density ; Population Dynamics ; }, abstract = {Hundreds of clinical studies have demonstrated associations between the human microbiome and disease, yet fundamental questions remain on how we can generalize this knowledge. Results from individual studies can be inconsistent, and comparing published data is further complicated by a lack of standard processing and analysis methods. Here we introduce the MicrobiomeHD database, which includes 28 published case-control gut microbiome studies spanning ten diseases. We perform a cross-disease meta-analysis of these studies using standardized methods. We find consistent patterns characterizing disease-associated microbiome changes. Some diseases are associated with over 50 genera, while most show only 10-15 genus-level changes. Some diseases are marked by the presence of potentially pathogenic microbes, whereas others are characterized by a depletion of health-associated bacteria. Furthermore, we show that about half of genera associated with individual studies are bacteria that respond to more than one disease. Thus, many associations found in case-control studies are likely not disease-specific but rather part of a non-specific, shared response to health and disease.}, } @article {pmid29202045, year = {2017}, author = {Mortimer, TD and Annis, DS and O'Neill, MB and Bohr, LL and Smith, TM and Poinar, HN and Mosher, DF and Pepperell, CS}, title = {Adaptation in a Fibronectin Binding Autolysin of Staphylococcus saprophyticus.}, journal = {mSphere}, volume = {2}, number = {6}, pages = {}, doi = {10.1128/mSphere.00511-17}, pmid = {29202045}, issn = {2379-5042}, support = {R01 AI113287/AI/NIAID NIH HHS/United States ; T32 GM007215/GM/NIGMS NIH HHS/United States ; }, abstract = {Human-pathogenic bacteria are found in a variety of niches, including free-living, zoonotic, and microbiome environments. Identifying bacterial adaptations that enable invasive disease is an important means of gaining insight into the molecular basis of pathogenesis and understanding pathogen emergence. Staphylococcus saprophyticus, a leading cause of urinary tract infections, can be found in the environment, food, animals, and the human microbiome. We identified a selective sweep in the gene encoding the Aas adhesin, a key virulence factor that binds host fibronectin. We hypothesize that the mutation under selection (aas_2206A>C) facilitates colonization of the urinary tract, an environment where bacteria are subject to strong shearing forces. The mutation appears to have enabled emergence and expansion of a human-pathogenic lineage of S. saprophyticus. These results demonstrate the power of evolutionary genomic approaches in discovering the genetic basis of virulence and emphasize the pleiotropy and adaptability of bacteria occupying diverse niches. IMPORTANCEStaphylococcus saprophyticus is an important cause of urinary tract infections (UTI) in women; such UTI are common, can be severe, and are associated with significant impacts to public health. In addition to being a cause of human UTI, S. saprophyticus can be found in the environment, in food, and associated with animals. After discovering that UTI strains of S. saprophyticus are for the most part closely related to each other, we sought to determine whether these strains are specially adapted to cause disease in humans. We found evidence suggesting that a mutation in the gene aas is advantageous in the context of human infection. We hypothesize that the mutation allows S. saprophyticus to survive better in the human urinary tract. These results show how bacteria found in the environment can evolve to cause disease.}, } @article {pmid29197615, year = {2018}, author = {Mao, Q and Jiang, F and Yin, R and Wang, J and Xia, W and Dong, G and Ma, W and Yang, Y and Xu, L and Hu, J}, title = {Interplay between the lung microbiome and lung cancer.}, journal = {Cancer letters}, volume = {415}, number = {}, pages = {40-48}, doi = {10.1016/j.canlet.2017.11.036}, pmid = {29197615}, issn = {1872-7980}, abstract = {The human microbiome confers benefits or disease susceptibility to the human body through multiple pathways. Disruption of the symbiotic balance of the human microbiome is commonly found in systematic diseases such as diabetes, obesity, and chronic gastric diseases. Emerging evidence has suggested that dysbiosis of the microbiota may also play vital roles in carcinogenesis at multiple levels, e.g., by affecting metabolic, inflammatory, or immune pathways. Although the impact of the gut microbiome on the digestive cancer has been widely explored, few studies have investigated the interplay between the microbiome and lung cancer. Some recent studies have shown that certain microbes and microbiota dysbiosis are correlated with development of lung cancer. In this mini-review, we briefly summarize current research findings describing the relationship between the lung microbiome and lung cancer. We further discuss the potential mechanisms through which the lung microbiome may play a role in lung carcinogenesis and impact lung cancer treatment. A better knowledge of the interplay between the lung microbiome and lung cancer may promote the development of innovative strategies for early prevention and personalized treatment in lung cancer.}, } @article {pmid29196353, year = {2017}, author = {Moffatt, MF and Cookson, WO}, title = {The lung microbiome in health and disease.}, journal = {Clinical medicine (London, England)}, volume = {17}, number = {6}, pages = {525-529}, doi = {10.7861/clinmedicine.17-6-525}, pmid = {29196353}, issn = {1473-4893}, mesh = {Asthma/microbiology ; Bronchiectasis/microbiology ; Cystic Fibrosis/microbiology ; Humans ; Lung/*microbiology ; Lung Diseases/*microbiology ; Metagenomics ; *Microbiota/genetics ; Pulmonary Disease, Chronic Obstructive/microbiology ; RNA, Ribosomal, 16S/genetics ; }, abstract = {The Human Microbiome Project began 10 years ago, leading to a significant growth in understanding of the role the human microbiome plays in health and disease. In this article, we explain with an emphasis on the lung, the origins of microbiome research. We discuss how 16S rRNA gene sequencing became the first major molecular tool to examine the bacterial communities present within the human body. We highlight the pitfalls of molecular-based studies, such as false findings resulting from contamination, and the limitations of 16S rRNA gene sequencing. Knowledge about the lung microbiome has evolved from initial scepticism to the realisation that it might have a significant influence on many illnesses. We also discuss the lung microbiome in the context of disease by giving examples of important respiratory conditions. In addition, we draw attention to the challenges for metagenomic studies of respiratory samples and the importance of systematic bacterial isolation to enable host-microbiome interactions to be understood. We conclude by discussing how knowledge of the lung microbiome impacts current clinical diagnostics.}, } @article {pmid29183332, year = {2017}, author = {Hall, AB and Yassour, M and Sauk, J and Garner, A and Jiang, X and Arthur, T and Lagoudas, GK and Vatanen, T and Fornelos, N and Wilson, R and Bertha, M and Cohen, M and Garber, J and Khalili, H and Gevers, D and Ananthakrishnan, AN and Kugathasan, S and Lander, ES and Blainey, P and Vlamakis, H and Xavier, RJ and Huttenhower, C}, title = {A novel Ruminococcus gnavus clade enriched in inflammatory bowel disease patients.}, journal = {Genome medicine}, volume = {9}, number = {1}, pages = {103}, doi = {10.1186/s13073-017-0490-5}, pmid = {29183332}, issn = {1756-994X}, support = {U54 DK102557/DK/NIDDK NIH HHS/United States ; U54DE023798//National Institutes of Health (US)/ ; P30 DK043351/DK/NIDDK NIH HHS/United States ; P30DK43351//National Institute of Diabetes and Digestive and Kidney Diseases/ ; R01 DK092405/DK/NIDDK NIH HHS/United States ; U54 DE023798/DE/NIDCR NIH HHS/United States ; K99 DK113224/DK/NIDDK NIH HHS/United States ; R01DK92405//National Institute of Diabetes and Digestive and Kidney Diseases/ ; MCB-1453942//National Science Foundation (US)/ ; }, mesh = {Adult ; Aged ; Feces/microbiology ; Gastrointestinal Microbiome/genetics ; Genome, Bacterial ; Humans ; Inflammatory Bowel Diseases/*microbiology ; Middle Aged ; Oxidative Stress ; Phylogeny ; Ruminococcus/genetics/*isolation & purification ; Species Specificity ; Young Adult ; }, abstract = {BACKGROUND: Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the gastrointestinal tract that is associated with changes in the gut microbiome. Here, we sought to identify strain-specific functional correlates with IBD outcomes.

METHODS: We performed metagenomic sequencing of monthly stool samples from 20 IBD patients and 12 controls (266 total samples). These were taxonomically profiled with MetaPhlAn2 and functionally profiled using HUMAnN2. Differentially abundant species were identified using MaAsLin and strain-specific pangenome haplotypes were analyzed using PanPhlAn.

RESULTS: We found a significantly higher abundance in patients of facultative anaerobes that can tolerate the increased oxidative stress of the IBD gut. We also detected dramatic, yet transient, blooms of Ruminococcus gnavus in IBD patients, often co-occurring with increased disease activity. We identified two distinct clades of R. gnavus strains, one of which is enriched in IBD patients. To study functional differences between these two clades, we augmented the R. gnavus pangenome by sequencing nine isolates from IBD patients. We identified 199 IBD-specific, strain-specific genes involved in oxidative stress responses, adhesion, iron-acquisition, and mucus utilization, potentially conferring an adaptive advantage for this R. gnavus clade in the IBD gut.

CONCLUSIONS: This study adds further evidence to the hypothesis that increased oxidative stress may be a major factor shaping the dysbiosis of the microbiome observed in IBD and suggests that R. gnavus may be an important member of the altered gut community in IBD.}, } @article {pmid29178920, year = {2017}, author = {Nash, AK and Auchtung, TA and Wong, MC and Smith, DP and Gesell, JR and Ross, MC and Stewart, CJ and Metcalf, GA and Muzny, DM and Gibbs, RA and Ajami, NJ and Petrosino, JF}, title = {The gut mycobiome of the Human Microbiome Project healthy cohort.}, journal = {Microbiome}, volume = {5}, number = {1}, pages = {153}, doi = {10.1186/s40168-017-0373-4}, pmid = {29178920}, issn = {2049-2618}, support = {P30 DK056338/DK/NIDDK NIH HHS/United States ; U54 HG003273/HG/NHGRI NIH HHS/United States ; 2 U54 HG003273//National Human Genome Research Institute/ ; }, mesh = {Candida/classification/genetics/isolation & purification ; Cohort Studies ; DNA, Ribosomal Spacer/genetics ; Feces/microbiology ; Fungi/classification/genetics/*isolation & purification ; Gastrointestinal Microbiome/*genetics ; Genetic Variation ; *Healthy Volunteers ; High-Throughput Nucleotide Sequencing/methods ; Humans ; Malassezia/classification/genetics/isolation & purification ; Metagenomics/methods ; *Microbiota ; *Mycobiome ; RNA, Ribosomal, 18S/genetics ; Saccharomyces/classification/genetics/isolation & purification ; Sequence Analysis, DNA ; }, abstract = {BACKGROUND: Most studies describing the human gut microbiome in healthy and diseased states have emphasized the bacterial component, but the fungal microbiome (i.e., the mycobiome) is beginning to gain recognition as a fundamental part of our microbiome. To date, human gut mycobiome studies have primarily been disease centric or in small cohorts of healthy individuals. To contribute to existing knowledge of the human mycobiome, we investigated the gut mycobiome of the Human Microbiome Project (HMP) cohort by sequencing the Internal Transcribed Spacer 2 (ITS2) region as well as the 18S rRNA gene.

RESULTS: Three hundred seventeen HMP stool samples were analyzed by ITS2 sequencing. Fecal fungal diversity was significantly lower in comparison to bacterial diversity. Yeast dominated the samples, comprising eight of the top 15 most abundant genera. Specifically, fungal communities were characterized by a high prevalence of Saccharomyces, Malassezia, and Candida, with S. cerevisiae, M. restricta, and C. albicans operational taxonomic units (OTUs) present in 96.8, 88.3, and 80.8% of samples, respectively. There was a high degree of inter- and intra-volunteer variability in fungal communities. However, S. cerevisiae, M. restricta, and C. albicans OTUs were found in 92.2, 78.3, and 63.6% of volunteers, respectively, in all samples donated over an approximately 1-year period. Metagenomic and 18S rRNA gene sequencing data agreed with ITS2 results; however, ITS2 sequencing provided greater resolution of the relatively low abundance mycobiome constituents.

CONCLUSIONS: Compared to bacterial communities, the human gut mycobiome is low in diversity and dominated by yeast including Saccharomyces, Malassezia, and Candida. Both inter- and intra-volunteer variability in the HMP cohort were high, revealing that unlike bacterial communities, an individual's mycobiome is no more similar to itself over time than to another person's. Nonetheless, several fungal species persisted across a majority of samples, evidence that a core gut mycobiome may exist. ITS2 sequencing data provided greater resolution of the mycobiome membership compared to metagenomic and 18S rRNA gene sequencing data, suggesting that it is a more sensitive method for studying the mycobiome of stool samples.}, } @article {pmid29177119, year = {2017}, author = {Wilantho, A and Deekaew, P and Srisuttiyakorn, C and Tongsima, S and Somboonna, N}, title = {Diversity of bacterial communities on the facial skin of different age-group Thai males.}, journal = {PeerJ}, volume = {5}, number = {}, pages = {e4084}, doi = {10.7717/peerj.4084}, pmid = {29177119}, issn = {2167-8359}, abstract = {Background: Skin microbiome varies from person to person due to a combination of various factors, including age, biogeography, sex, cosmetics and genetics. Many skin disorders appear to be related to the resident microflora, yet databases of facial skin microbiome of many biogeographies, including Thai, are limited.

Methods: Metagenomics derived B-RISA and 16S rRNA gene sequencing was utilized to identify the culture-independent bacterial diversity on Thai male faces (cheek and forehead areas). Skin samples were categorized (grouped) into (i) normal (teenage.hea) and (ii) acne-prone (teenage.acn) young adults, and normal (iii) middle-aged (middle.hea) and (iv) elderly (elderly.hea) adults.

Results: The 16S rRNA gene sequencing was successful as the sequencing depth had an estimated >98% genus coverage of the true community. The major diversity was found between the young and elderly adults in both cheek and forehead areas, followed by that between normal and acne young adults. Detection of representative characteristics indicated that bacteria from the order Rhizobiales, genera Sphingomonas and Pseudoalteromonas, distinguished the elderly.hea microbiota, along the clinical features of wrinkles and pores. Prediction of the metabolic potential revealed reduced metabolic pathways involved in replication and repair, nucleotide metabolism and genetic translation in the elderly.hea compared with that in the teenage.hea. For young adults, some unique compositions such as abundance of Propionibacterium acnes and Staphylococcus epidermidis, with a minor diversity between normal and acne skins, were detected. The metabolic potentials of the acne vs. normal young adults showed that teenage.acn was low in many cellular processes (e.g., cell motility and environmental adaptation), but high in carbohydrate metabolism, which could support acne growth. Moreover, comparison with the age-matched males from the US (Boulder, Colorado) to gain insight into the diversity across national biogeography, revealed differences in the distribution pattern of species, although common bacteria were present in both biogeographical samples. Furthermore, B-RISA served as a crosscheck result to the 16S rRNA gene sequencing (i.e., differences between teenage and elderly microbiota).

Conclusions: This study revealed and compared the microbial diversity on different aged Thai male faces, and included analyses for representing the bacterial flora, the clinical skin characteristics, and comparison with the US age-matched. The results represent the first skin microbiota of Thai males, and helps the design of a large-scale skin microbiome study of Thais. The findings of the diversity among ages, skin type and national biogeography supported the importance of these traits in the skin microbiome and in developing a safe and sustainable treatment for acne and aging skin diseases.}, } @article {pmid29175577, year = {2018}, author = {McMillan, A and Renaud, JB and Burgess, KMN and Orimadegun, AE and Akinyinka, OO and Allen, SJ and Miller, JD and Reid, G and Sumarah, MW}, title = {Aflatoxin exposure in Nigerian children with severe acute malnutrition.}, journal = {Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association}, volume = {111}, number = {}, pages = {356-362}, doi = {10.1016/j.fct.2017.11.030}, pmid = {29175577}, issn = {1873-6351}, mesh = {Aflatoxins/administration & dosage/chemistry/*toxicity ; Child Nutrition Disorders/blood/*complications/*epidemiology ; Child, Preschool ; Humans ; Infant ; Molecular Structure ; Nigeria ; }, abstract = {Aflatoxin exposure is an important public health concern in sub-Saharan Africa as well as parts of Latin America and Asia. In addition to hepatocellular carcinoma, chronic aflatoxin exposure is believed to play a role in childhood growth impairment. The most reliable biomarker of chronic aflatoxin exposure is the aflatoxin-albumin adduct, as measured by ELISA or isotope dilution mass spectrometry (IDMS). In this report, we have used high resolution LC-MS/MS with IDMS to quantitate AFB1-lysine in an extremely vulnerable population of Nigerian children suffering from severe acute malnutrition. To increase the sensitivity and reliability of the analyses, a labelled AFB1-13C615N2-lysine internal standard was synthesized. AFB1-lysine concentrations in this population ranged between 0.2 and 59.2 pg/mg albumin, with a median value of 2.6 pg/mg albumin. AFB1-lysine concentrations were significantly higher in stunted children (median = 4.6 pg/mg) compared to non-stunted (1.2 pg/mg), as well as in children with severe acute malnutrition (4.3 pg/mg) compared to controls (0.8 pg/mg). The median concentrations were also higher in children with kwashiorkor (6.3 pg/mg) compared to those suffering from marasmus (0.9 pg/mg). This is the first report of the use of high-resolution mass spectrometry to quantitate AFB1-lysine in humans.}, } @article {pmid29155236, year = {2018}, author = {Al, KF and Bisanz, JE and Gloor, GB and Reid, G and Burton, JP}, title = {Evaluation of sampling and storage procedures on preserving the community structure of stool microbiota: A simple at-home toilet-paper collection method.}, journal = {Journal of microbiological methods}, volume = {144}, number = {}, pages = {117-121}, doi = {10.1016/j.mimet.2017.11.014}, pmid = {29155236}, issn = {1872-8359}, abstract = {BACKGROUND: The increasing interest on the impact of the gut microbiota on health and disease has resulted in multiple human microbiome-related studies emerging. However, multiple sampling methods are being used, making cross-comparison of results difficult. To avoid additional clinic visits and increase patient recruitment to these studies, there is the potential to utilize at-home stool sampling. The aim of this pilot study was to compare simple self-sampling collection and storage methods.

METHODS: To simulate storage conditions, stool samples from three volunteers were freshly collected, placed on toilet tissue, and stored at four temperatures (-80, 7, 22 and 37°C), either dry or in the presence of a stabilization agent (RNAlater®) for 3 or 7days. Using 16S rRNA gene sequencing by Illumina, the effect of storage variations for each sample was compared to a reference community from fresh, unstored counterparts. Fastq files may be accessed in the NCBI Sequence Read Archive: Bioproject ID PRJNA418287.

RESULTS: Microbial diversity and composition were not significantly altered by any storage method. Samples were always separable based on participant, regardless of storage method suggesting there was no need for sample preservation by a stabilization agent.

DISCUSSION: In summary, if immediate sample processing is not feasible, short term storage of unpreserved stool samples on toilet paper offers a reliable way to assess the microbiota composition by 16S rRNA gene sequencing.}, } @article {pmid29152585, year = {2017}, author = {d'Hennezel, E and Abubucker, S and Murphy, LO and Cullen, TW}, title = {Total Lipopolysaccharide from the Human Gut Microbiome Silences Toll-Like Receptor Signaling.}, journal = {mSystems}, volume = {2}, number = {6}, pages = {}, doi = {10.1128/mSystems.00046-17}, pmid = {29152585}, issn = {2379-5077}, abstract = {Cohabitation of microbial communities with the host enables the formation of a symbiotic relationship that maintains homeostasis in the gut and beyond. One prevailing model suggests that this relationship relies on the capacity of host cells and tissues to remain tolerant to the strong immune stimulation generated by the microbiota such as the activation of Toll-like receptor 4 (TLR4) pathways by lipopolysaccharide (LPS). Indeed, gut microbial LPS is thought to be one of the most potent activators of innate immune signaling and an important mediator of the microbiome's influence on host physiology. In this study, we performed computational and experimental analyses of healthy human fecal samples to examine the TLR4 signaling capacity of the gut microbiota. These analyses revealed that an immunoinhibitory activity of LPS, conserved across the members of the order Bacteroidales and derived from an underacylated structural feature, silences TLR4 signaling for the entire consortium of organisms inhabiting the human gut. Comparative analysis of metagenomic data from the Human Microbiome Project and healthy-donor samples indicates that immune silencing via LPS is a microbe-intrinsic feature in all healthy adults. These findings challenge the current belief that robust TLR4 signaling is a feature of the microbiome and demonstrate that microbiome-derived LPS has the ability to facilitate host tolerance of gut microbes. These findings have broad implications for how we model host-microbe interactions and for our understanding of microbiome-linked disease. IMPORTANCE While the ability for humans to host a complex microbial ecosystem is an essential property of life, the mechanisms allowing for immune tolerance of such a large microbial load are not completely understood and are currently the focus of intense research. This study shows that an important proinflammatory pathway that is commonly triggered by pathogenic bacteria upon interaction with the host is, in fact, actively repressed by the bacteria of the gut microbiome, supporting the idea that beneficial microbes themselves contribute to the immune tolerance in support of homeostasis. These findings are important for two reasons. First, many currently assume that proinflammatory signaling by lipopolysaccharide is a fundamental feature of the gut flora. This assumption influences greatly how host-microbiome interactions are theoretically modeled but also how they are experimentally studied, by using robust TLR signaling conditions to simulate commensals. Second, elucidation of the mechanisms that support host-microbe tolerance is key to the development of therapeutics for both intestinal and systemic inflammatory disorders.}, } @article {pmid29152409, year = {2017}, author = {Tosi, L and Sridhara, V and Yang, Y and Guan, D and Shpilker, P and Segata, N and Larman, HB and Parekkadan, B}, title = {Long-adapter single-strand oligonucleotide probes for the massively multiplexed cloning of kilobase genome regions.}, journal = {Nature biomedical engineering}, volume = {1}, number = {}, pages = {}, doi = {10.1038/s41551-017-0092}, pmid = {29152409}, issn = {2157-846X}, support = {K01 DK087770/DK/NIDDK NIH HHS/United States ; R01 EB012521/EB/NIBIB NIH HHS/United States ; R21 CA202875/CA/NCI NIH HHS/United States ; U24 AI118633/AI/NIAID NIH HHS/United States ; }, abstract = {As the catalogue of sequenced genomes and metagenomes continues to grow, massively parallel approaches for the comprehensive and functional analysis of gene products and regulatory elements are becoming increasingly valuable. Current strategies to synthesize or clone complex libraries of DNA sequences are limited by the length of the DNA targets, throughput and cost. Here, we show that long-adapter single-strand oligonucleotide (LASSO) probes can capture and clone thousands of kilobase DNA fragments in a single reaction. As a proof-of-principle, we simultaneously cloned >3,000 bacterial open reading frames (ORFs) from E. coli genomic DNA (spanning 400-5,000 bp targets). Targets were enriched up to a median of ~60-fold compared to non-targeted genomic regions. At a cutoff of 3 times the median non-target reads per kilobase of genetic element per million reads, ~75% of the targeted ORFs were successfully captured. We also show that LASSO probes can clone human ORFs from complementary DNA, and an ORF library from a human-microbiome sample. LASSO probes could be used for the preparation of long-read sequencing libraries and for massively multiplexed cloning.}, } @article {pmid29151903, year = {2017}, author = {Yamamura, K and Baba, Y and Miyake, K and Nakamura, K and Shigaki, H and Mima, K and Kurashige, J and Ishimoto, T and Iwatsuki, M and Sakamoto, Y and Yamashita, Y and Yoshida, N and Watanabe, M and Baba, H}, title = {Fusobacterium nucleatum in gastroenterological cancer: Evaluation of measurement methods using quantitative polymerase chain reaction and a literature review.}, journal = {Oncology letters}, volume = {14}, number = {6}, pages = {6373-6378}, doi = {10.3892/ol.2017.7001}, pmid = {29151903}, issn = {1792-1074}, abstract = {The human microbiome Fusobacterium nucleatum, which primarily inhabits the oral cavity, causes periodontal disease and has also been implicated in the development of colorectal cancer. However, whether F. nucleatum is present in other gastroenterological cancer tissues remains to be elucidated. The present study evaluated whether quantitative polymerase chain reaction (qPCR) assays were able to detect F. nucleatum DNA and measure the quantity of F. nucleatum DNA in esophageal, gastric, pancreatic and liver cancer tissues. The accuracy of the qPCR assay was determined from a calibration curve using DNA extracted from cells from the oral cavity. Formalin-fixed paraffin-embedded (FFPE) tumor tissues from 20 patients with gastroenterological [esophageal (squamous cell carcinoma), gastric, colorectal, pancreatic and liver] cancer and 20 matched normal tissues were evaluated for F. nucleatum DNA content. The cycle threshold values in the qPCR assay for F. nucleatum and solute carrier organic anion transporter family member 2A1 (reference sample) decreased linearly with the quantity of input DNA (r2>0.99). The F. nucleatum detection rate in esophageal, gastric and colorectal cancer tissues were 20% (4/20), 10% (2/20) and 45% (9/20), respectively. F. nucleatum was not detected in liver and pancreatic cancer tissues. The qPCR results from the frozen and FFPE tissues were consistent. Notably, F. nucleatum was detected at a higher level in superficial areas compared with the invasive areas. F. nucleatum in esophageal, gastric and colorectal cancer tissues was evaluated by qPCR using FFPE tissues. F. nucleatum may be involved in the development of esophageal, gastric and colorectal cancer.}, } @article {pmid29145477, year = {2017}, author = {Parajuli, A and Grönroos, M and Kauppi, S and Płociniczak, T and Roslund, MI and Galitskaya, P and Laitinen, OH and Hyöty, H and Jumpponen, A and Strömmer, R and Romantschuk, M and Hui, N and Sinkkonen, A}, title = {The abundance of health-associated bacteria is altered in PAH polluted soils-Implications for health in urban areas?.}, journal = {PloS one}, volume = {12}, number = {11}, pages = {e0187852}, doi = {10.1371/journal.pone.0187852}, pmid = {29145477}, issn = {1932-6203}, mesh = {Bacteria/*isolation & purification ; Finland ; Gas Chromatography-Mass Spectrometry ; Polycyclic Aromatic Hydrocarbons/*analysis ; *Soil Microbiology ; Soil Pollutants/*analysis ; }, abstract = {Long-term exposure to polyaromatic hydrocarbons (PAHs) has been connected to chronic human health disorders. It is also well-known that i) PAH contamination alters soil bacterial communities, ii) human microbiome is associated with environmental microbiome, and iii) alteration in the abundance of members in several bacterial phyla is associated with adverse or beneficial human health effects. We hypothesized that soil pollution by PAHs altered soil bacterial communities that had known associations with human health. The rationale behind our study was to increase understanding and potentially facilitate reconsidering factors that lead to health disorders in areas characterized by PAH contamination. Large containers filled with either spruce forest soil, pine forest soil, peat, or glacial sand were left to incubate or contaminated with creosote. Biological degradation of PAHs was monitored using GC-MS, and the bacterial community composition was analyzed using 454 pyrosequencing. Proteobacteria had higher and Actinobacteria and Bacteroidetes had lower relative abundance in creosote contaminated soils than in non-contaminated soils. Earlier studies have demonstrated that an increase in the abundance of Proteobacteria and decreased abundance of the phyla Actinobacteria and Bacteroidetes are particularly associated with adverse health outcomes and immunological disorders. Therefore, we propose that pollution-induced shifts in natural soil bacterial community, like in PAH-polluted areas, can contribute to the prevalence of chronic diseases. We encourage studies that simultaneously address the classic "adverse toxin effect" paradigm and our novel "altered environmental microbiome" hypothesis.}, } @article {pmid29141044, year = {2017}, author = {Chen, I and Kelkar, YD and Gu, Y and Zhou, J and Qiu, X and Wu, H}, title = {High-dimensional linear state space models for dynamic microbial interaction networks.}, journal = {PloS one}, volume = {12}, number = {11}, pages = {e0187822}, doi = {10.1371/journal.pone.0187822}, pmid = {29141044}, issn = {1932-6203}, support = {T32 AI083206/AI/NIAID NIH HHS/United States ; HHSN272201200005C/AI/NIAID NIH HHS/United States ; UL1 TR002001/TR/NCATS NIH HHS/United States ; R01 AI087135/AI/NIAID NIH HHS/United States ; P30 AI078498/AI/NIAID NIH HHS/United States ; }, mesh = {Algorithms ; Female ; Host-Pathogen Interactions ; Humans ; *Microbial Interactions ; *Models, Theoretical ; Vagina/microbiology ; }, abstract = {Medical researchers are increasingly interested in knowing how the complex community of micro-organisms living on human body impacts human health. Key to this is to understand how the microbes interact with each other. Time-course studies on human microbiome indicate that the composition of microbiome changes over short time periods, primarily as a consequence of synergistic and antagonistic interactions of the members of the microbiome with each other and with the environment. Knowledge of the abundance of bacteria-which are the predominant members of the human microbiome-in such time-course studies along with appropriate mathematical models will allow us to identify key dynamic interaction networks within the microbiome. However, the high-dimensional nature of these data poses significant challenges to the development of such mathematical models. We propose a high-dimensional linear State Space Model (SSM) with a new Expectation-Regularization-Maximization (ERM) algorithm to construct a dynamic Microbial Interaction Network (MIN). System noise and measurement noise can be separately specified through SSMs. In order to deal with the problem of high-dimensional parameter space in the SSMs, the proposed new ERM algorithm employs the idea of the adaptive LASSO-based variable selection method so that the sparsity property of MINs can be preserved. We performed simulation studies to evaluate the proposed ERM algorithm for variable selection. The proposed method is applied to identify the dynamic MIN from a time-course vaginal microbiome study of women. This method is amenable to future developments, which may include interactions between microbes and the environment.}, } @article {pmid29140991, year = {2017}, author = {Schwager, E and Mallick, H and Ventz, S and Huttenhower, C}, title = {A Bayesian method for detecting pairwise associations in compositional data.}, journal = {PLoS computational biology}, volume = {13}, number = {11}, pages = {e1005852}, doi = {10.1371/journal.pcbi.1005852}, pmid = {29140991}, issn = {1553-7358}, support = {U54 DK102557/DK/NIDDK NIH HHS/United States ; }, mesh = {Algorithms ; *Bayes Theorem ; Computational Biology/*methods ; *Computer Simulation ; Ecology ; Humans ; Markov Chains ; Microbiota ; *Models, Biological ; Proteobacteria ; }, abstract = {Compositional data consist of vectors of proportions normalized to a constant sum from a basis of unobserved counts. The sum constraint makes inference on correlations between unconstrained features challenging due to the information loss from normalization. However, such correlations are of long-standing interest in fields including ecology. We propose a novel Bayesian framework (BAnOCC: Bayesian Analysis of Compositional Covariance) to estimate a sparse precision matrix through a LASSO prior. The resulting posterior, generated by MCMC sampling, allows uncertainty quantification of any function of the precision matrix, including the correlation matrix. We also use a first-order Taylor expansion to approximate the transformation from the unobserved counts to the composition in order to investigate what characteristics of the unobserved counts can make the correlations more or less difficult to infer. On simulated datasets, we show that BAnOCC infers the true network as well as previous methods while offering the advantage of posterior inference. Larger and more realistic simulated datasets further showed that BAnOCC performs well as measured by type I and type II error rates. Finally, we apply BAnOCC to a microbial ecology dataset from the Human Microbiome Project, which in addition to reproducing established ecological results revealed unique, competition-based roles for Proteobacteria in multiple distinct habitats.}, } @article {pmid29136663, year = {2017}, author = {Zhang, Y and Alekseyenko, AV}, title = {Phylogenic inference using alignment-free methods for applications in microbial community surveys using 16s rRNA gene.}, journal = {PloS one}, volume = {12}, number = {11}, pages = {e0187940}, doi = {10.1371/journal.pone.0187940}, pmid = {29136663}, issn = {1932-6203}, mesh = {Microbiota/*genetics ; *Phylogeny ; RNA, Ribosomal, 16S/*genetics ; }, abstract = {The diversity of microbiota is best explored by understanding the phylogenetic structure of the microbial communities. Traditionally, sequence alignment has been used for phylogenetic inference. However, alignment-based approaches come with significant challenges and limitations when massive amounts of data are analyzed. In the recent decade, alignment-free approaches have enabled genome-scale phylogenetic inference. Here we evaluate three alignment-free methods: ACS, CVTree, and Kr for phylogenetic inference with 16s rRNA gene data. We use a taxonomic gold standard to compare the accuracy of alignment-free phylogenetic inference with that of common microbiome-wide phylogenetic inference pipelines based on PyNAST and MUSCLE alignments with FastTree and RAxML. We re-simulate fecal communities from Human Microbiome Project data to evaluate the performance of the methods on datasets with properties of real data. Our comparisons show that alignment-free methods are not inferior to alignment-based methods in giving accurate and robust phylogenic trees. Moreover, consensus ensembles of alignment-free phylogenies are superior to those built from alignment-based methods in their ability to highlight community differences in low power settings. In addition, the overall running times of alignment-based and alignment-free phylogenetic inference are comparable. Taken together our empirical results suggest that alignment-free methods provide a viable approach for microbiome-wide phylogenetic inference.}, } @article {pmid29134286, year = {2018}, author = {Rossi, C and Marzano, V and Consalvo, A and Zucchelli, M and Levi Mortera, S and Casagrande, V and Mavilio, M and Sacchetta, P and Federici, M and Menghini, R and Urbani, A and Ciavardelli, D}, title = {Proteomic and metabolomic characterization of streptozotocin-induced diabetic nephropathy in TIMP3-deficient mice.}, journal = {Acta diabetologica}, volume = {55}, number = {2}, pages = {121-129}, doi = {10.1007/s00592-017-1074-y}, pmid = {29134286}, issn = {1432-5233}, support = {GR-2011-02346912//Italian Ministry of Health/ ; 2-SRA-2014-262-Q-R//Juvenile Diabetes Research Foundation JDRF/ ; Fondazione Roma 2008//Fondazione Roma/ ; }, mesh = {Animals ; Diabetes Mellitus, Experimental/chemically induced/complications/*metabolism ; Diabetic Nephropathies/chemically induced/genetics/*metabolism/pathology ; Kidney/metabolism ; Kidney Failure, Chronic/chemically induced/genetics/*metabolism/pathology ; Lipid Metabolism ; Metabolome ; *Metabolomics ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Proteome/analysis/metabolism ; *Proteomics ; Streptozocin ; Tissue Inhibitor of Metalloproteinase-3/*genetics ; }, abstract = {AIMS: The tissue inhibitor of metalloproteinase TIMP3 is a stromal protein that restrains the activity of both protease and receptor in the extracellular matrix and has been found to be down-regulated in diabetic nephropathy (DN), the leading cause of end-stage renal disease in developed countries.

METHODS: In order to gain deeper insights on the association of loss of TIMP3 and DN, we performed differential proteomic analysis of kidney and blood metabolic profiling of wild-type and Timp3-knockout mice before and after streptozotocin (STZ) treatment, widely used to induce insulin deficiency and hyperglycemia.

RESULTS: Kidney proteomic data and blood metabolic profiles suggest significant alterations of peroxisomal and mitochondrial fatty acids β-oxidation in Timp3-knockout mice compared to wild-type mice under basal condition. These alterations were exacerbated in response to STZ treatment.

CONCLUSIONS: Proteomic and metabolomic approaches showed that loss of TIMP3 alone or in combination with STZ treatment results in significant alterations of kidney lipid metabolism and peripheral acylcarnitine levels, supporting the idea that loss of TIMP3 may generate a phenotype more prone to DN.}, } @article {pmid29134235, year = {2018}, author = {Ma, ZS}, title = {Correction to: The P/N (Positive-to-Negative Links) Ratio in Complex Networks-A Promising In Silico Biomarker for Detecting Changes Occurring in the Human Microbiome.}, journal = {Microbial ecology}, volume = {75}, number = {4}, pages = {1074}, doi = {10.1007/s00248-017-1107-7}, pmid = {29134235}, issn = {1432-184X}, abstract = {The original version of this article unfortunately contained a missing image. The flowchart was not captured in PDF version. The original article was corrected.}, } @article {pmid29129355, year = {2018}, author = {Li, J and Fu, R and Yang, Y and Horz, HP and Guan, Y and Lu, Y and Lou, H and Tian, L and Zheng, S and Liu, H and Shi, M and Tang, K and Wang, S and Xu, S}, title = {A metagenomic approach to dissect the genetic composition of enterotypes in Han Chinese and two Muslim groups.}, journal = {Systematic and applied microbiology}, volume = {41}, number = {1}, pages = {1-12}, doi = {10.1016/j.syapm.2017.09.006}, pmid = {29129355}, issn = {1618-0984}, mesh = {Asian Continental Ancestry Group ; Bacteria/*classification/*genetics ; Cluster Analysis ; DNA, Bacterial/chemistry/genetics ; DNA, Ribosomal/chemistry/genetics ; Ethnic Groups ; *Gastrointestinal Microbiome ; Genetic Association Studies ; Healthy Volunteers ; Humans ; Islam ; Lysophospholipase/genetics ; *Metagenomics ; *Microbiota ; Phylogeny ; Polymorphism, Single Nucleotide ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; }, abstract = {Distinct enterotypes have been observed in the human gut but little is known about the genetic basis of the microbiome. Moreover, it is not clear how many genetic differences exist between enterotypes within or between populations. In this study, both the 16S rRNA gene and the metagenomes of the gut microbiota were sequenced from 48 Han Chinese, 48 Kazaks, and 96 Uyghurs, and taxonomies were assigned after de novo assembly. Single nucleotide polymorphisms were also identified by referring to data from the Human Microbiome Project. Systematic analysis of the gut communities in terms of their abundance and genetic composition was also performed, together with a genome-wide association study of the host genomes. The gut microbiota of 192 subjects was clearly classified into two enterotypes (Bacteroides and Prevotella). Interestingly, both enterotypes showed a clear genetic differentiation in terms of their functional catalogue of genes, especially for genes involved in amino acid and carbohydrate metabolism. In addition, several differentiated genera and genes were found among the three populations. Notably, one human variant (rs878394) was identified that showed significant association with the abundance of Prevotella, which is linked to LYPLAL1, a gene associated with body fat distribution, the waist-hip ratio and insulin sensitivity. Taken together, considerable differentiation was observed in gut microbes between enterotypes and among populations that was reflected in both the taxonomic composition and the genetic makeup of their functional genes, which could have been influenced by a variety of factors, such as diet and host genetic variation.}, } @article {pmid29122007, year = {2017}, author = {Li, S and Fuhler, GM and Bn, N and Jose, T and Bruno, MJ and Peppelenbosch, MP and Konstantinov, SR}, title = {Pancreatic cyst fluid harbors a unique microbiome.}, journal = {Microbiome}, volume = {5}, number = {1}, pages = {147}, doi = {10.1186/s40168-017-0363-6}, pmid = {29122007}, issn = {2049-2618}, mesh = {Aged ; Bacteria/classification/genetics/*isolation & purification ; Bacterial Translocation ; Bacteroides/genetics/isolation & purification ; DNA, Bacterial/genetics/*isolation & purification ; Female ; Fusobacterium/genetics/isolation & purification ; Gastrointestinal Tract/microbiology ; High-Throughput Nucleotide Sequencing ; Humans ; Male ; Microbiota/*genetics ; Middle Aged ; Neoplastic Processes ; Pancreas/microbiology/physiopathology ; Pancreatic Cyst/*microbiology ; Phylogeny ; Polymerase Chain Reaction ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Staphylococcus/genetics/isolation & purification ; }, abstract = {BACKGROUND: It is clear that specific intestinal bacteria are involved in the development of different premalignant conditions along the gastrointestinal tract. An analysis of the microbial constituents in the context of pancreatic cystic lesions has, however, as yet not been performed. This consideration prompted us to explore whether endoscopically obtained pancreatic cyst fluids (PCF) contain bacterial DNA and to determine the genera of bacteria present in such material.

METHODS: Total DNA was isolated from 69 PCF samples. Bacterial 16S rRNA gene-specific PCR was performed followed by Sanger sequencing and de novo deep sequencing for the V3-V4 variable region of 16S rRNA gene.

RESULTS: We observed that 98.2% of the samples were positive in conventional PCR, and that 100% of selected PCF samples (n = 33) were positive for bacterial microbiota as determined by next generation sequencing (NGS). Comprehensive NGS data analysis of PCF showed the presence of 408 genera of bacteria, of which 17 bacterial genera were uniquely abundant to PCF, when compared to the Human Microbiome Project (HMP) database and 15 bacterial microbiota were uniquely abundant in HMP only. Bacteroides spp., Escherichia/Shigella spp., and Acidaminococcus spp. which were predominant in PCF, while also a substantial Staphylococcus spp. and Fusobacterium spp. component was detected.

CONCLUSION: These results reveal and characterize an apparently specific bacterial ecosystem in pancreatic cyst fluid samples and may reflect the local microbiota in the pancreas. Some taxa with potential deleterious functions are present in the bacterial abundance profiles, suggesting that the unique microbiome in this specific niche may contribute to neoplastic processes in the pancreas. Further studies are needed to explore the intricate relationship between pathophysiological status in the host pancreas and its microbiota.}, } @article {pmid29120742, year = {2017}, author = {Maruvada, P and Leone, V and Kaplan, LM and Chang, EB}, title = {The Human Microbiome and Obesity: Moving beyond Associations.}, journal = {Cell host & microbe}, volume = {22}, number = {5}, pages = {589-599}, doi = {10.1016/j.chom.2017.10.005}, pmid = {29120742}, issn = {1934-6069}, mesh = {Animals ; Diet ; Dysbiosis/complications ; Energy Intake ; Energy Metabolism/physiology ; Gastrointestinal Microbiome/physiology ; Gastrointestinal Tract/microbiology ; Humans ; Microbiota/*physiology ; Models, Animal ; *Obesity/microbiology ; }, abstract = {Mounting evidence indicates that the gut microbiome responds to diet, antibiotics, and other external stimuli with speed and high precision and in ways that impact a variety of metabolic conditions including obesity and non-alcoholic fatty liver disease. Despite a decade of research establishing a strong association between the gut microbiota and obesity in humans, a causal relationship and the underlying mechanism remain outstanding. Several technological and methodological limitations in obesity and microbiome research have made it difficult to establish causality in this complex relationship. Additionally, limited collaborative interaction between microbiome and obesity researchers has delayed progress. Here, we discuss the current status of microbiome research as it relates to understanding obesity from the perspective of both communities, outline the underlying research challenges, and suggest directions to advance the obesity-microbiome field as a whole, with particular emphasis on the development of microbiome-targeted therapies for obesity prevention and treatment.}, } @article {pmid29120486, year = {2017}, author = {Miossec, MJ and Valenzuela, SL and Mendez, KN and Castro-Nallar, E}, title = {Computational Methods for Human Microbiome Analysis.}, journal = {Current protocols in microbiology}, volume = {47}, number = {}, pages = {1E.14.1-1E.14.17}, doi = {10.1002/cpmc.41}, pmid = {29120486}, issn = {1934-8533}, mesh = {Computational Biology/*methods ; Humans ; Metagenomics/*methods ; *Microbiota ; }, abstract = {As the field of microbiomics advances, the burden of computational work that scientists need to perform in order to extract biological insight has grown accordingly. Likewise, while human microbiome analyses are increasingly shifting toward a greater integration of various high-throughput data types, a core number of methods form the basis of nearly every study. In this unit, we present step-by-step protocols for five core stages of human microbiome research. The protocols presented in this unit provide a base case for human microbiome analysis, complete with sufficient detail for researchers to tailor certain aspects of the protocols to the specificities of their data. © 2017 by John Wiley & Sons, Inc.}, } @article {pmid29116650, year = {2017}, author = {Bik, EM and Ugalde, JA and Cousins, J and Goddard, AD and Richman, J and Apte, ZS}, title = {Microbial biotransformations in the human distal gut.}, journal = {British journal of pharmacology}, volume = {}, number = {}, pages = {}, doi = {10.1111/bph.14085}, pmid = {29116650}, issn = {1476-5381}, abstract = {The human distal gut is home to a rich and dense microbial community with representatives of all three domains of life which are intricately connected with our physiology and health. The combined genomes of these microbes, collectively called the human microbiome, vastly expand the metabolic capacities of our own genome, allowing us to break down and extract energy from dietary compounds that human enzymes cannot digest. In addition, the variable composition of these communities and their biotransformations might explain inter-individual differences in toxicities, tolerances and efficacies for certain drugs. Recent advances in sequencing technologies and bioinformatics have provided exciting new insights into the genomes of our microbial symbionts, their functional capacities and the interactions between these microbes and their human host. This review summarizes the metabolic conversions of dietary components and pharmaceuticals that take place in the human distal gut, as well as their implications for human health.}, } @article {pmid29112885, year = {2018}, author = {Neville, BA and Forster, SC and Lawley, TD}, title = {Commensal Koch's postulates: establishing causation in human microbiota research.}, journal = {Current opinion in microbiology}, volume = {42}, number = {}, pages = {47-52}, doi = {10.1016/j.mib.2017.10.001}, pmid = {29112885}, issn = {1879-0364}, abstract = {Advances in high-throughput sequencing technologies and the development of sophisticated bioinformatics analysis methods, algorithms, and pipelines to handle the large amounts of data generated have driven the field of human microbiome research forward. This specialist knowledge has been crucial to thoroughly mine the human gut microbiota, particularly in the absence of methods for the routine cultivation of most enteric microorganisms. In recent years, however, significant efforts have been made to address the 'great plate count anomaly' and to overcome the barriers to cultivation of the fastidious and mostly strictly anaerobic bacteria that reside in the human gut. As a result, many new species have been discovered, characterised, genome sequenced, and deposited in culture collections. These continually expanding resources enable experimental investigation of the human gut microbiota, validation of hypotheses made with sequence-based analyses, and phenotypic characterisation of its constituent microbes. Herein we propose a variant of Koch's postulates, aimed at providing a framework to establish causation in microbiome studies, with a particular focus on demonstrating the health-promoting role of the commensal gut microbiota.}, } @article {pmid29107345, year = {2018}, author = {Luca, F and Kupfer, SS and Knights, D and Khoruts, A and Blekhman, R}, title = {Functional Genomics of Host-Microbiome Interactions in Humans.}, journal = {Trends in genetics : TIG}, volume = {34}, number = {1}, pages = {30-40}, doi = {10.1016/j.tig.2017.10.001}, pmid = {29107345}, issn = {0168-9525}, support = {P30 CA022453/CA/NCI NIH HHS/United States ; R01 GM109215/GM/NIGMS NIH HHS/United States ; }, abstract = {The human microbiome has been linked to various host phenotypes and has been implicated in many complex human diseases. Recent genome-wide association studies (GWASs) have used microbiome variation as a complex trait and have uncovered human genetic variants that are associated with the microbiome. Here we summarize results from these studies and illustrate potential regulatory mechanisms by which host genetic variation can interact with microbiome composition. We argue that, similar to human GWASs, it is important to use functional genomics techniques to gain a mechanistic understanding of causal host-microbiome interactions and their role in human disease. We highlight experimental, functional, and computational genomics methodologies for the study of the genomic basis of host-microbiome interactions and describe how these approaches can be utilized to explain how human genetic variation can modulate the effects of the microbiome on the host.}, } @article {pmid29106667, year = {2018}, author = {Oliveira, FS and Brestelli, J and Cade, S and Zheng, J and Iodice, J and Fischer, S and Aurrecoechea, C and Kissinger, JC and Brunk, BP and Stoeckert, CJ and Fernandes, GR and Roos, DS and Beiting, DP}, title = {MicrobiomeDB: a systems biology platform for integrating, mining and analyzing microbiome experiments.}, journal = {Nucleic acids research}, volume = {46}, number = {D1}, pages = {D684-D691}, doi = {10.1093/nar/gkx1027}, pmid = {29106667}, issn = {1362-4962}, abstract = {MicrobiomeDB (http://microbiomeDB.org) is a data discovery and analysis platform that empowers researchers to fully leverage experimental variables to interrogate microbiome datasets. MicrobiomeDB was developed in collaboration with the Eukaryotic Pathogens Bioinformatics Resource Center (http://EuPathDB.org) and leverages the infrastructure and user interface of EuPathDB, which allows users to construct in silico experiments using an intuitive graphical 'strategy' approach. The current release of the database integrates microbial census data with sample details for nearly 14 000 samples originating from human, animal and environmental sources, including over 9000 samples from healthy human subjects in the Human Microbiome Project (http://portal.ihmpdcc.org/). Query results can be statistically analyzed and graphically visualized via interactive web applications launched directly in the browser, providing insight into microbial community diversity and allowing users to identify taxa associated with any experimental covariate.}, } @article {pmid29105344, year = {2017}, author = {Gutiérrez-Barranquero, JA and Reen, FJ and Parages, ML and McCarthy, R and Dobson, ADW and O'Gara, F}, title = {Disruption of N-acyl-homoserine lactone-specific signalling and virulence in clinical pathogens by marine sponge bacteria.}, journal = {Microbial biotechnology}, volume = {}, number = {}, pages = {}, doi = {10.1111/1751-7915.12867}, pmid = {29105344}, issn = {1751-7915}, abstract = {In recent years, the marine environment has been the subject of increasing attention from biotechnological and pharmaceutical industries. A combination of unique physicochemical properties and spatial niche-specific substrates, in wide-ranging and extreme habitats, underscores the potential of the marine environment to deliver on functionally novel bioactivities. One such area of ongoing research is the discovery of compounds that interfere with the cell-cell signalling process called quorum sensing (QS). Described as the next generation of antimicrobials, these compounds can target virulence and persistence of clinically relevant pathogens, independent of any growth-limiting effects. Marine sponges are a rich source of microbial diversity, with dynamic populations in a symbiotic relationship. In this study, we have harnessed the QS inhibition (QSI) potential of marine sponge microbiota and through culture-based discovery have uncovered small molecule signal mimics that neutralize virulence phenotypes in clinical pathogens. This study describes for the first time a marine sponge Psychrobacter sp. isolate B98C22 that blocks QS signalling, while also reporting dual QS/QSI activity in the Pseudoalteromonas sp. J10 and ParacoccusJM45. Isolation of novel QSI activities has significant potential for future therapeutic development, of particular relevance in the light of the pending perfect storm of antibiotic resistance meeting antibiotic drug discovery decline.}, } @article {pmid29104759, year = {2017}, author = {Guthrie, L and Gupta, S and Daily, J and Kelly, L}, title = {Human microbiome signatures of differential colorectal cancer drug metabolism.}, journal = {NPJ biofilms and microbiomes}, volume = {3}, number = {}, pages = {27}, doi = {10.1038/s41522-017-0034-1}, pmid = {29104759}, issn = {2055-5008}, support = {T32 GM007491/GM/NIGMS NIH HHS/United States ; }, abstract = {It is well appreciated that microbial metabolism of drugs can influence treatment efficacy. Microbial β-glucuronidases in the gut can reactivate the excreted, inactive metabolite of irinotecan, a first-line chemotherapeutic for metastatic colorectal cancer. Reactivation causes adverse drug responses, including severe diarrhea. However, a direct connection between irinotecan metabolism and the composition of an individual's gut microbiota has not previously been made. Here, we report quantitative evidence of inter-individual variability in microbiome metabolism of the inactive metabolite of irinotecan to its active form. We identify a high turnover microbiota metabotype with potentially elevated risk for irinotecan-dependent adverse drug responses. We link the high turnover metabotype to unreported microbial β-glucuronidases; inhibiting these enzymes may decrease irinotecan-dependent adverse drug responses in targeted subsets of patients. In total, this study reveals metagenomic mining of the microbiome, combined with metabolomics, as a non-invasive approach to develop biomarkers for colorectal cancer treatment outcomes.}, } @article {pmid29101674, year = {2017}, author = {Caminer, AC and Haberman, R and Scher, JU}, title = {Human microbiome, infections, and rheumatic disease.}, journal = {Clinical rheumatology}, volume = {36}, number = {12}, pages = {2645-2653}, doi = {10.1007/s10067-017-3875-3}, pmid = {29101674}, issn = {1434-9949}, support = {K23AR064318//National Institute of Arthritis and Musculoskeletal and Skin Diseases/ ; R03AR072182//National Institute of Arthritis and Musculoskeletal and Skin Diseases/ ; }, mesh = {Animals ; Arthritis, Rheumatoid/immunology/*microbiology ; Disease Models, Animal ; Humans ; *Microbiota ; Spondylarthritis/immunology/*microbiology ; }, abstract = {Microbes have coevolved with their human hosts for millions of years and are vital to their normal development and homoeostasis. It is now clear that there is direct and indirect cross talk between the microbiome and host immune responses. However, the exact mechanisms for this microbial influence in disease pathogenesis remain elusive and are now a major research focus.}, } @article {pmid29099090, year = {2017}, author = {Leccioli, V and Oliveri, M and Romeo, M and Berretta, M and Rossi, P}, title = {A New Proposal for the Pathogenic Mechanism of Non-Coeliac/Non-Allergic Gluten/Wheat Sensitivity: Piecing Together the Puzzle of Recent Scientific Evidence.}, journal = {Nutrients}, volume = {9}, number = {11}, pages = {}, doi = {10.3390/nu9111203}, pmid = {29099090}, issn = {2072-6643}, mesh = {Animals ; Bifidobacterium/*growth & development/metabolism ; Butyrates/metabolism ; Celiac Disease/classification/diagnosis/immunology/*microbiology ; *Dysbiosis ; Evidence-Based Medicine ; Firmicutes/*growth & development/metabolism ; *Gastrointestinal Microbiome ; Glutens/*administration & dosage/immunology ; Humans ; Intestinal Absorption ; Intestines/*microbiology ; Permeability ; Prognosis ; Risk Factors ; Triticum/*adverse effects/immunology ; Wheat Hypersensitivity/classification/diagnosis/immunology/*microbiology ; }, abstract = {Non-coeliac/non-allergic gluten/wheat sensitivity (NCG/WS) is a gluten-related disorder, the pathogenesis of which remains unclear. Recently, the involvement of an increased intestinal permeability has been recognized in the onset of this clinical condition. However, mechanisms through which it takes place are still unclear. In this review, we attempt to uncover these mechanisms by providing, for the first time, an integrated vision of recent scientific literature, resulting in a new hypothesis about the pathogenic mechanisms involved in NCG/WS. According to this, the root cause of NCG/WS is a particular dysbiotic profile characterized by decreased butyrate-producing-Firmicutes and/or Bifidobacteria, leading to low levels of intestinal butyrate. Beyond a critical threshold of the latter, a chain reaction of events and vicious circles occurs, involving other protagonists such as microbial lipopolysaccharide (LPS), intestinal alkaline phosphatase (IAP) and wheat α-amylase trypsin inhibitors (ATIs). NCG/WS is likely to be a multi-factor-onset disorder, probably transient and preventable, related to quality and balance of the diet, and not to the presence of gluten in itself. If future studies confirm our proposal, this would have important implications both for the definition of the disease, as well as for the prevention and therapeutic-nutritional management of individuals with NCG/WS.}, } @article {pmid29098118, year = {2017}, author = {Kodukula, K and Faller, DV and Harpp, DN and Kanara, I and Pernokas, J and Pernokas, M and Powers, WR and Soukos, NS and Steliou, K and Moos, WH}, title = {Gut Microbiota and Salivary Diagnostics: The Mouth Is Salivating to Tell Us Something.}, journal = {BioResearch open access}, volume = {6}, number = {1}, pages = {123-132}, doi = {10.1089/biores.2017.0020}, pmid = {29098118}, issn = {2164-7844}, abstract = {The microbiome of the human body represents a symbiosis of microbial networks spanning multiple organ systems. Bacteria predominantly represent the diversity of human microbiota, but not to be forgotten are fungi, viruses, and protists. Mounting evidence points to the fact that the "microbial signature" is host-specific and relatively stable over time. As our understanding of the human microbiome and its relationship to the health of the host increases, it is becoming clear that many and perhaps most chronic conditions have a microbial involvement. The oral and gastrointestinal tract microbiome constitutes the bulk of the overall human microbial load, and thus presents unique opportunities for advancing human health prognosis, diagnosis, and therapy development. This review is an attempt to catalog a broad diversity of recent evidence and focus it toward opportunities for prevention and treatment of debilitating illnesses.}, } @article {pmid29095820, year = {2017}, author = {Marzano, V and Mancinelli, L and Bracaglia, G and Del Chierico, F and Vernocchi, P and Di Girolamo, F and Garrone, S and Tchidjou Kuekou, H and D'Argenio, P and Dallapiccola, B and Urbani, A and Putignani, L}, title = {"Omic" investigations of protozoa and worms for a deeper understanding of the human gut "parasitome".}, journal = {PLoS neglected tropical diseases}, volume = {11}, number = {11}, pages = {e0005916}, doi = {10.1371/journal.pntd.0005916}, pmid = {29095820}, issn = {1935-2735}, mesh = {Animals ; Entamoeba histolytica/genetics/metabolism ; Gastrointestinal Microbiome ; Gastrointestinal Tract/*parasitology ; *Genomics ; Giardia/genetics/metabolism ; Helminths/genetics/physiology ; *Host-Parasite Interactions ; Humans ; *Metabolomics ; Mice ; Parasites/*physiology ; *Proteomics ; Taenia solium/genetics/metabolism ; }, abstract = {The human gut has been continuously exposed to a broad spectrum of intestinal organisms, including viruses, bacteria, fungi, and parasites (protozoa and worms), over millions of years of coevolution, and plays a central role in human health. The modern lifestyles of Western countries, such as the adoption of highly hygienic habits, the extensive use of antimicrobial drugs, and increasing globalisation, have dramatically altered the composition of the gut milieu, especially in terms of its eukaryotic "citizens." In the past few decades, numerous studies have highlighted the composition and role of human intestinal bacteria in physiological and pathological conditions, while few investigations exist on gut parasites and particularly on their coexistence and interaction with the intestinal microbiota. Studies of the gut "parasitome" through "omic" technologies, such as (meta)genomics, transcriptomics, proteomics, and metabolomics, are herein reviewed to better understand their role in the relationships between intestinal parasites, host, and resident prokaryotes, whether pathogens or commensals. Systems biology-based profiles of the gut "parasitome" under physiological and severe disease conditions can indeed contribute to the control of infectious diseases and offer a new perspective of omics-assisted tropical medicine.}, } @article {pmid29094223, year = {2017}, author = {Schorpion, A and Kolasinski, SL}, title = {Can Probiotic Supplements Improve Outcomes in Rheumatoid Arthritis?.}, journal = {Current rheumatology reports}, volume = {19}, number = {11}, pages = {73}, doi = {10.1007/s11926-017-0696-y}, pmid = {29094223}, issn = {1534-6307}, mesh = {Arthritis, Rheumatoid/*drug therapy/microbiology ; *Dietary Supplements ; Humans ; Microbiota/*drug effects ; Probiotics/pharmacology/*therapeutic use ; Treatment Outcome ; }, abstract = {PURPOSE OF REVIEW: The purpose of this review is to frame the discussion of the potential use of probiotics for the management of rheumatoid arthritis (RA) in the historical and scientific context linking the human microbiota to the etiology, pathogenesis, and treatment of RA. Given this context, the review then details the clinical trials that have been carried out so far that have tried to address the question.

RECENT FINDINGS: A variety of laboratory and clinical observations link the flora of the oral cavity and lower gastrointestinal tract with citrullination, as well as immunological alterations that may contribute to the risk of developing RA. Clinical trials to date have been small and mostly short term. Statistically significant change in certain disparate clinical endpoints has been reported, but these endpoints have varied from study to study and have been of limited clinical significance. No consistent, robust impact on patient reported, or laboratory outcome measures has emerged from clinical trials so far. There remain theoretical reasons to further investigate the use of probiotics as adjunctive therapies for autoimmune disease, but changes in trial design may be needed to reveal the benefit of this intervention.}, } @article {pmid29075243, year = {2017}, author = {Ambrosi, C and Scribano, D and Aleandri, M and Zagaglia, C and Di Francesco, L and Putignani, L and Palamara, AT}, title = {Acinetobacter baumannii Virulence Traits: A Comparative Study of a Novel Sequence Type with Other Italian Endemic International Clones.}, journal = {Frontiers in microbiology}, volume = {8}, number = {}, pages = {1977}, doi = {10.3389/fmicb.2017.01977}, pmid = {29075243}, issn = {1664-302X}, abstract = {Carbapenem-resistant Acinetobacter baumannii (CRAb) have emerged in recent decades as major causes of nosocomial infections. Resistance is mainly due to overexpression of intrinsic and/or acquired carbapenemases, especially oxacillinases (OXA). In Italy, although the sequence type (ST) 2 and the ST78 are the most frequently detected, we recently reported ST632, a single locus variant of ST2. Therefore, this study was aimed at unraveling common bacterial surface virulence factors involved in pathogenesis and antibiotic resistance in representative CRAb of these ST genotypes. Outer membrane protein (OMP) composition together with motility, biofilm formation, in vitro adherence to, invasion of, and survival within pneumocytes were analyzed. Differently from the carbapenem-susceptible reference strain ATCC 17978, either overexpressed OXA-51 or both OXA-23 and OXA-51 co-purified with OMPs in CRAb. This tight association ensures their maximal concentration on the inner surface of the outer membrane to provide the best protection against carbapenems. These findings led us to propose for the first time a common behavior of OXA enzymes in CRAb. Despite the presence of both OmpA and phosphorylcholine-porinD and the ability of all the strains to adhere to cells, invasion, and survival within pneumocytes was shown only by ST2 and ST78 isolates, sharing the highest number of identified OMPs. Conversely, notwithstanding genetic and OMPs similarities with ST2, ST632 was unable to invade and survive within epithelial cells. Overall, our study shows that different STs share a specific OMP composition, also shaped by overexpressed OXA, that is needed for invasiveness and survival of CRAb.}, } @article {pmid29064808, year = {2017}, author = {Krajewska-Włodarczyk, M}, title = {[The role of the human microbiom in the pathogenesis of rheumatoid arthritis - a literature review].}, journal = {Wiadomosci lekarskie (Warsaw, Poland : 1960)}, volume = {70}, number = {4}, pages = {798-803}, pmid = {29064808}, issn = {0043-5147}, mesh = {Arthritis, Rheumatoid/*microbiology ; Autoimmune Diseases/microbiology ; Dysbiosis/*microbiology ; *Gastrointestinal Microbiome ; Humans ; *Microbiota ; }, abstract = {Rheumatoid arthritis is a chronic, progressive, autoimmune disease with numerous articular, extra-articular and systemic manifestations. The cause of rheumatoid arthritis is multifactorial including genetic and environmental factors. Recent advantages in sequencing techniques have allowed the deep characterization of the human microbiota. Available evidence confirms the existence of an association between dysbiosis and rheumatoid arthritis but it still remains unclear whether alterations in the microbiome are a pathogenic cause or an effect of autoimmune disease. In patients with rheumatoid arthritis the most supported association between disease and microbiota is with the oral dysbiosis usually observed in patients with periodontitis. Given the strong variability and abundance of microbes living in close relation with human host, it becomes a difficult task to define what should be considered the favorable microbiome. There is need for broader studies to establish how the human microbiome contributes to disease susceptibility, and to characterize the role of microbial diversity in the pathogenesis of rheumatoid arthritis, disease manifestation, and progression. The identification of dysbiosis specific for rheumatoid arthritis and the understanding of the dynamic interaction between microbiota and their host may help in establishing an individualized management for each patient with rheumatoid arthritis, and achieve a better efficacy of the therapy.}, } @article {pmid29062070, year = {2018}, author = {Cookson, WOCM and Cox, MJ and Moffatt, MF}, title = {New opportunities for managing acute and chronic lung infections.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {2}, pages = {111-120}, doi = {10.1038/nrmicro.2017.122}, pmid = {29062070}, issn = {1740-1534}, support = {G1000758//Medical Research Council/United Kingdom ; }, abstract = {Lung diseases caused by microbial infections affect hundreds of millions of children and adults throughout the world. In Western populations, the treatment of lung infections is a primary driver of antibiotic resistance. Traditional therapeutic strategies have been based on the premise that the healthy lung is sterile and that infections grow in a pristine environment. As a consequence, rapid advances in our understanding of the composition of the microbiota of the skin and bowel have not yet been matched by studies of the respiratory tree. The recognition that the lungs are as populated with microorganisms as other mucosal surfaces provides the opportunity to reconsider the mechanisms and management of lung infections. Molecular analyses of the lung microbiota are revealing profound adverse responses to widespread antibiotic use, urbanization and globalization. This Opinion article proposes how technologies and concepts flowing from the Human Microbiome Project can transform the diagnosis and treatment of common lung diseases.}, } @article {pmid29061894, year = {2017}, author = {Aktipis, A and Maley, CC}, title = {Cooperation and cheating as innovation: insights from cellular societies.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {372}, number = {1735}, pages = {}, doi = {10.1098/rstb.2016.0421}, pmid = {29061894}, issn = {1471-2970}, support = {P01 CA091955/CA/NCI NIH HHS/United States ; R01 CA140657/CA/NCI NIH HHS/United States ; R01 CA185138/CA/NCI NIH HHS/United States ; }, mesh = {*Biological Evolution ; Cooperative Behavior ; *Eukaryota ; Microbial Interactions ; *Microbiota ; Models, Biological ; }, abstract = {The capacity to innovate is often considered a defining feature of human societies, but it is not a capacity that is unique to human societies: innovation occurs in cellular societies as well. Cellular societies such as multicellular bodies and microbial communities, including the human microbiome, are capable of innovation in response to novel opportunities and threats. Multicellularity represents a suite of innovations for cellular cooperation, but multicellularity also opened up novel opportunities for cells to cheat, exploiting the infrastructure and resources of the body. Multicellular bodies evolve less quickly than the cells within them, leaving them vulnerable to cellular innovations that can lead to cancer and infections. In order to counter these threats, multicellular bodies deploy additional innovations including the adaptive immune system and the development of partnerships with preferred microbial partners. What can we learn from examining these innovations in cooperation and cheating in cellular societies? First, innovation in social systems involves a constant tension between novel mechanisms that enable greater size and complexity of cooperative entities and novel ways of cheating. Second, cultivating cooperation with partners who can rapidly and effectively innovate (such as microbes) is important for large entities including multicellular bodies. And third, multicellularity enabled cells to manage risk socially, allowing organisms to survive in challenging environments where life would otherwise be impossible. Throughout, we ask how insights from cellular societies might be translated into new innovations in human health and medicine, promoting and protecting the cellular cooperation that makes us viable multicellular organisms.This article is part of the themed issue 'Process and pattern in innovations from cells to societies'.}, } @article {pmid29042495, year = {2017}, author = {Maier, TV and Lucio, M and Lee, LH and VerBerkmoes, NC and Brislawn, CJ and Bernhardt, J and Lamendella, R and McDermott, JE and Bergeron, N and Heinzmann, SS and Morton, JT and González, A and Ackermann, G and Knight, R and Riedel, K and Krauss, RM and Schmitt-Kopplin, P and Jansson, JK}, title = {Impact of Dietary Resistant Starch on the Human Gut Microbiome, Metaproteome, and Metabolome.}, journal = {mBio}, volume = {8}, number = {5}, pages = {}, doi = {10.1128/mBio.01343-17}, pmid = {29042495}, issn = {2150-7511}, support = {RC1 DK086472/DK/NIDDK NIH HHS/United States ; }, mesh = {Bacteria/classification/drug effects/genetics/growth & development ; DNA, Bacterial/chemistry/genetics ; DNA, Ribosomal/chemistry/genetics ; Diet/methods ; Gastrointestinal Microbiome/*drug effects ; Humans ; Metabolome/*drug effects ; Metabolomics ; Microbiota/*drug effects ; Proteome/*drug effects ; Proteomics ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Starch/*administration & dosage ; }, abstract = {Diet can influence the composition of the human microbiome, and yet relatively few dietary ingredients have been systematically investigated with respect to their impact on the functional potential of the microbiome. Dietary resistant starch (RS) has been shown to have health benefits, but we lack a mechanistic understanding of the metabolic processes that occur in the gut during digestion of RS. Here, we collected samples during a dietary crossover study with diets containing large or small amounts of RS. We determined the impact of RS on the gut microbiome and metabolic pathways in the gut, using a combination of "omics" approaches, including 16S rRNA gene sequencing, metaproteomics, and metabolomics. This multiomics approach captured changes in the abundance of specific bacterial species, proteins, and metabolites after a diet high in resistant starch (HRS), providing key insights into the influence of dietary interventions on the gut microbiome. The combined data showed that a high-RS diet caused an increase in the ratio of Firmicutes to Bacteroidetes, including increases in relative abundances of some specific members of the Firmicutes and concurrent increases in enzymatic pathways and metabolites involved in lipid metabolism in the gut.IMPORTANCE This work was undertaken to obtain a mechanistic understanding of the complex interplay between diet and the microorganisms residing in the intestine. Although it is known that gut microbes play a key role in digestion of the food that we consume, the specific contributions of different microorganisms are not well understood. In addition, the metabolic pathways and resultant products of metabolism during digestion are highly complex. To address these knowledge gaps, we used a combination of molecular approaches to determine the identities of the microorganisms in the gut during digestion of dietary starch as well as the metabolic pathways that they carry out. Together, these data provide a more complete picture of the function of the gut microbiome in digestion, including links between an RS diet and lipid metabolism and novel linkages between specific gut microbes and their metabolites and proteins produced in the gut.}, } @article {pmid29040806, year = {2018}, author = {Burch, JM and Mashayekh, S and Wykoff, DD and Grimes, CL}, title = {Bacterial Derived Carbohydrates Bind Cyr1 and Trigger Hyphal Growth in Candida albicans.}, journal = {ACS infectious diseases}, volume = {4}, number = {1}, pages = {53-58}, doi = {10.1021/acsinfecdis.7b00154}, pmid = {29040806}, issn = {2373-8227}, support = {P20 GM104316/GM/NIGMS NIH HHS/United States ; P30 GM110758/GM/NIGMS NIH HHS/United States ; }, abstract = {The dimorphic yeast Candida albicans is the most common pathogenic fungus found in humans. While this species is normally commensal, a morphological switch from budding yeast to filamentous hyphae allows the fungi to invade epithelial cells and cause infections. The phenotypic change is controlled by the adenylyl cyclase, Cyr1. Interestingly, this protein contains a leucine-rich repeat (LRR) domain, which is commonly found in innate immune receptors from plants and animals. A functional and pure LRR domain was obtained in high yields from E. coli expression. Utilizing a surface plasmon resonance assay, the LRR was found to bind diverse bacterial derived carbohydrates with high affinity. This domain is capable of binding fragments of peptidoglycan, a carbohydrate polymer component of the bacterial cell wall, as well as anthracyclines produced by Streptomyces, leading to hyphae formation. These findings add another dimension to the human microbiome, taking into account yeast-bacteria interactions that occur in the host.}, } @article {pmid29040451, year = {2018}, author = {Chen, J and King, E and Deek, R and Wei, Z and Yu, Y and Grill, D and Ballman, K and Stegle, O}, title = {An omnibus test for differential distribution analysis of microbiome sequencing data.}, journal = {Bioinformatics (Oxford, England)}, volume = {34}, number = {4}, pages = {643-651}, doi = {10.1093/bioinformatics/btx650}, pmid = {29040451}, issn = {1367-4811}, abstract = {Motivation: One objective of human microbiome studies is to identify differentially abundant microbes across biological conditions. Previous statistical methods focus on detecting the shift in the abundance and/or prevalence of the microbes and treat the dispersion (spread of the data) as a nuisance. These methods also assume that the dispersion is the same across conditions, an assumption which may not hold in presence of sample heterogeneity. Moreover, the widespread outliers in the microbiome sequencing data make existing parametric models not overly robust. Therefore, a robust and powerful method that allows covariate-dependent dispersion and addresses outliers is still needed for differential abundance analysis.

Results: We introduce a novel test for differential distribution analysis of microbiome sequencing data by jointly testing the abundance, prevalence and dispersion. The test is built on a zero-inflated negative binomial regression model and winsorized count data to account for zero-inflation and outliers. Using simulated data and real microbiome sequencing datasets, we show that our test is robust across various biological conditions and overall more powerful than previous methods.

R package is available at https://github.com/jchen1981/MicrobiomeDDA.

Contact: chen.jun2@mayo.edu or zhiwei@njit.edu.

Supplementary information: Supplementary data are available at Bioinformatics online.}, } @article {pmid29039256, year = {2017}, author = {Woodworth, MH and Sitchenko, KL and Carpentieri, C and Friedman-Moraco, RJ and Wang, T and Kraft, CS}, title = {Ethical Considerations in Microbial Therapeutic Clinical Trials.}, journal = {The New bioethics : a multidisciplinary journal of biotechnology and the body}, volume = {23}, number = {3}, pages = {210-218}, doi = {10.1080/20502877.2017.1387386}, pmid = {29039256}, issn = {2050-2885}, support = {UL1 TR000454/TR/NCATS NIH HHS/United States ; }, mesh = {Clinical Trials as Topic/*ethics ; Clostridium Infections/*therapy ; Clostridium difficile/isolation & purification ; Fecal Microbiota Transplantation/*ethics ; Gastrointestinal Microbiome ; Humans ; }, abstract = {As understanding of the human microbiome improves, novel therapeutic targets to improve human health with microbial therapeutics will continue to expand. We outline key considerations of balancing risks and benefits, optimising access, returning key results to research participants, and potential conflicts of interest.}, } @article {pmid29038470, year = {2017}, author = {Ma, ZS and Ye, D}, title = {Trios-promising in silico biomarkers for differentiating the effect of disease on the human microbiome network.}, journal = {Scientific reports}, volume = {7}, number = {1}, pages = {13259}, doi = {10.1038/s41598-017-12959-3}, pmid = {29038470}, issn = {2045-2322}, abstract = {Recent advances in the HMP (human microbiome project) research have revealed profound implications of the human microbiome to our health and diseases. We postulated that there should be distinctive features associated with healthy and/or diseased microbiome networks. Following Occam's razor principle, we further hypothesized that triangle motifs or trios, arguably the simplest motif in a complex network of the human microbiome, should be sufficient to detect changes that occurred in the diseased microbiome. Here we test our hypothesis with six HMP datasets that cover five major human microbiome sites (gut, lung, oral, skin, and vaginal). The tests confirm our hypothesis and demonstrate that the trios involving the special nodes (e.g., most abundant OTU or MAO, and most dominant OTU or MDO, etc.) and interactions types (positive vs. negative) can be a powerful tool to differentiate between healthy and diseased microbiome samples. Our findings suggest that 12 kinds of trios (especially, dominantly inhibitive trio with mixed strategy, dominantly inhibitive trio with pure strategy, and fully facilitative strategy) may be utilized as in silico biomarkers for detecting disease-associated changes in the human microbiome, and may play an important role in personalized precision diagnosis of the human microbiome associated diseases.}, } @article {pmid29030459, year = {2017}, author = {Ribado, JV and Ley, C and Haggerty, TD and Tkachenko, E and Bhatt, AS and Parsonnet, J}, title = {Household triclosan and triclocarban effects on the infant and maternal microbiome.}, journal = {EMBO molecular medicine}, volume = {9}, number = {12}, pages = {1732-1741}, doi = {10.15252/emmm.201707882}, pmid = {29030459}, issn = {1757-4684}, support = {K08 CA184420/CA/NCI NIH HHS/United States ; R01 HD063142/HD/NICHD NIH HHS/United States ; R21 ES023371/ES/NIEHS NIH HHS/United States ; T32 HG000044/HG/NHGRI NIH HHS/United States ; }, mesh = {Adult ; Anti-Infective Agents/*pharmacology ; Bacteria/genetics/isolation & purification ; Biodiversity ; Carbanilides/*pharmacology ; Chromatography, High Pressure Liquid ; DNA, Bacterial/chemistry/isolation & purification/metabolism ; Disinfectants/chemistry ; Drug Resistance, Bacterial ; Female ; Gastrointestinal Microbiome/*drug effects ; Humans ; Infant ; Liquid-Liquid Extraction ; Longitudinal Studies ; Proteobacteria/genetics/growth & development ; RNA, Ribosomal, 16S/chemistry/metabolism ; Sequence Analysis, DNA ; Toothpastes/chemistry ; Triclosan/isolation & purification/*pharmacology/urine ; }, abstract = {In 2016, the US Food and Drug Administration banned the use of specific microbicides in some household and personal wash products due to concerns that these chemicals might induce antibiotic resistance or disrupt human microbial communities. Triclosan and triclocarban (referred to as TCs) are the most common antimicrobials in household and personal care products, but the extent to which TC exposure perturbs microbial communities in humans, particularly during infant development, was unknown. We conducted a randomized intervention of TC-containing household and personal care products during the first year following birth to characterize whether TC exposure from wash products perturbs microbial communities in mothers and their infants. Longitudinal survey of the gut microbiota using 16S ribosomal RNA amplicon sequencing showed that TC exposure from wash products did not induce global reconstruction or loss of microbial diversity of either infant or maternal gut microbiotas. Broadly antibiotic-resistant species from the phylum Proteobacteria, however, were enriched in stool samples from mothers in TC households after the introduction of triclosan-containing toothpaste. When compared by urinary triclosan level, agnostic to treatment arm, infants with higher triclosan levels also showed an enrichment of Proteobacteria species. Despite the minimal effects of TC exposure from wash products on the gut microbial community of infants and adults, detected taxonomic differences highlight the need for consumer safety testing of antimicrobial self-care products on the human microbiome and on antibiotic resistance.}, } @article {pmid29028892, year = {2018}, author = {Weber, N and Liou, D and Dommer, J and MacMenamin, P and Quiñones, M and Misner, I and Oler, AJ and Wan, J and Kim, L and Coakley McCarthy, M and Ezeji, S and Noble, K and Hurt, DE}, title = {Nephele: a cloud platform for simplified, standardized and reproducible microbiome data analysis.}, journal = {Bioinformatics (Oxford, England)}, volume = {34}, number = {8}, pages = {1411-1413}, doi = {10.1093/bioinformatics/btx617}, pmid = {29028892}, issn = {1367-4811}, abstract = {Motivation: Widespread interest in the study of the microbiome has resulted in data proliferation and the development of powerful computational tools. However, many scientific researchers lack the time, training, or infrastructure to work with large datasets or to install and use command line tools.

Results: The National Institute of Allergy and Infectious Diseases (NIAID) has created Nephele, a cloud-based microbiome data analysis platform with standardized pipelines and a simple web interface for transforming raw data into biological insights. Nephele integrates common microbiome analysis tools as well as valuable reference datasets like the healthy human subjects cohort of the Human Microbiome Project (HMP). Nephele is built on the Amazon Web Services cloud, which provides centralized and automated storage and compute capacity, thereby reducing the burden on researchers and their institutions.

https://nephele.niaid.nih.gov and https://github.com/niaid/Nephele.

Contact: darrell.hurt@nih.gov.}, } @article {pmid29028668, year = {2018}, author = {Hager, CL and Ghannoum, MA}, title = {The mycobiome in HIV.}, journal = {Current opinion in HIV and AIDS}, volume = {13}, number = {1}, pages = {69-72}, doi = {10.1097/COH.0000000000000432}, pmid = {29028668}, issn = {1746-6318}, support = {R01 DE024228/DE/NIDCR NIH HHS/United States ; U01 AI105937/AI/NIAID NIH HHS/United States ; }, mesh = {HIV Infections/*pathology ; Humans ; *Microbiota ; Mouth/*microbiology ; *Mycobiome ; Respiratory System/*microbiology ; }, abstract = {PURPOSE OF REVIEW: There are a limited number of studies investigating the association between the microbiome and HIV. Although the majority of these published investigations have focused on the role of the bacterial community (bacteriome) in this setting, a handful of studies have also characterized the role of the mycobiome in HIV-infected individuals. This review will summarize the most recent reports pertaining to the role of the fungal community in HIV.

RECENT FINDINGS: Differences in the composition of the oral and respiratory mycobiome in HIV-infected individuals compared with uninfected individuals have been reported.

SUMMARY: Our review shows that studies investigating the role of the mycobiome in the setting of HIV are severely lacking. With recent advances in our understanding of the composition of the human microbiome, investigations into the role of the bacteria and fungus comprising the overall microbiota and how the two interact to influence each other and the host is crucial.}, } @article {pmid29022944, year = {2017}, author = {Lloyd-Price, J and Mahurkar, A and Rahnavard, G and Crabtree, J and Orvis, J and Hall, AB and Brady, A and Creasy, HH and McCracken, C and Giglio, MG and McDonald, D and Franzosa, EA and Knight, R and White, O and Huttenhower, C}, title = {Erratum: Strains, functions and dynamics in the expanded Human Microbiome Project.}, journal = {Nature}, volume = {551}, number = {7679}, pages = {256}, doi = {10.1038/nature24485}, pmid = {29022944}, issn = {1476-4687}, abstract = {This corrects the article DOI: 10.1038/nature23889.}, } @article {pmid29018902, year = {2018}, author = {Ma, ZS}, title = {The P/N (Positive-to-Negative Links) Ratio in Complex Networks-A Promising In Silico Biomarker for Detecting Changes Occurring in the Human Microbiome.}, journal = {Microbial ecology}, volume = {75}, number = {4}, pages = {1063-1073}, doi = {10.1007/s00248-017-1079-7}, pmid = {29018902}, issn = {1432-184X}, abstract = {Relatively little progress in the methodology for differentiating between the healthy and diseased microbiomes, beyond comparing microbial community diversities with traditional species richness or Shannon index, has been made. Network analysis has increasingly been called for the task, but most currently available microbiome datasets only allows for the construction of simple species correlation networks (SCNs). The main results from SCN analysis are a series of network properties such as network degree and modularity, but the metrics for these network properties often produce inconsistent evidence. We propose a simple new network property, the P/N ratio, defined as the ratio of positive links to the number of negative links in the microbial SCN. We postulate that the P/N ratio should reflect the balance between facilitative and inhibitive interactions among microbial species, possibly one of the most important changes occurring in diseased microbiome. We tested our hypothesis with five datasets representing five major human microbiome sites and discovered that the P/N ratio exhibits contrasting differences between healthy and diseased microbiomes and may be harnessed as an in silico biomarker for detecting disease-associated changes in the human microbiome, and may play an important role in personalized diagnosis of the human microbiome-associated diseases.}, } @article {pmid29018846, year = {2017}, author = {Mousa, WK and Athar, B and Merwin, NJ and Magarvey, NA}, title = {Antibiotics and specialized metabolites from the human microbiota.}, journal = {Natural product reports}, volume = {34}, number = {11}, pages = {1302-1331}, doi = {10.1039/c7np00021a}, pmid = {29018846}, issn = {1460-4752}, mesh = {*Anti-Bacterial Agents/isolation & purification/metabolism/pharmacology ; Humans ; *Microbiota ; Molecular Structure ; }, abstract = {Covering: 2000 to 2017Decades of research on human microbiota have revealed much of their taxonomic diversity and established their direct link to health and disease. However, the breadth of bioactive natural products secreted by our microbial partners remains unknown. Of particular interest are antibiotics produced by our microbiota to ward off invasive pathogens. Members of the human microbiota exclusively produce evolved small molecules with selective antimicrobial activity against human pathogens. Herein, we expand upon the current knowledge concerning antibiotics derived from human microbiota and their distribution across body sites. We analyze, using our in-house chem-bioinformatic tools and natural products database, the encoded antibiotic potential of the human microbiome. This compilation of information may create a foundation for the continued exploration of this intriguing resource of chemical diversity and expose challenges and future perspectives to accelerate the discovery rate of small molecules from the human microbiota.}, } @article {pmid29018189, year = {2017}, author = {Jie, Z and Xia, H and Zhong, SL and Feng, Q and Li, S and Liang, S and Zhong, H and Liu, Z and Gao, Y and Zhao, H and Zhang, D and Su, Z and Fang, Z and Lan, Z and Li, J and Xiao, L and Li, J and Li, R and Li, X and Li, F and Ren, H and Huang, Y and Peng, Y and Li, G and Wen, B and Dong, B and Chen, JY and Geng, QS and Zhang, ZW and Yang, H and Wang, J and Wang, J and Zhang, X and Madsen, L and Brix, S and Ning, G and Xu, X and Liu, X and Hou, Y and Jia, H and He, K and Kristiansen, K}, title = {The gut microbiome in atherosclerotic cardiovascular disease.}, journal = {Nature communications}, volume = {8}, number = {1}, pages = {845}, doi = {10.1038/s41467-017-00900-1}, pmid = {29018189}, issn = {2041-1723}, mesh = {Atherosclerosis/*microbiology ; Case-Control Studies ; Fermentation ; *Gastrointestinal Microbiome/drug effects ; Genome-Wide Association Study ; Humans ; Inflammation/microbiology ; Liver Cirrhosis/microbiology ; *Metagenome ; Metagenomics ; }, abstract = {The gut microbiota has been linked to cardiovascular diseases. However, the composition and functional capacity of the gut microbiome in relation to cardiovascular diseases have not been systematically examined. Here, we perform a metagenome-wide association study on stools from 218 individuals with atherosclerotic cardiovascular disease (ACVD) and 187 healthy controls. The ACVD gut microbiome deviates from the healthy status by increased abundance of Enterobacteriaceae and Streptococcus spp. and, functionally, in the potential for metabolism or transport of several molecules important for cardiovascular health. Although drug treatment represents a confounding factor, ACVD status, and not current drug use, is the major distinguishing feature in this cohort. We identify common themes by comparison with gut microbiome data associated with other cardiometabolic diseases (obesity and type 2 diabetes), with liver cirrhosis, and rheumatoid arthritis. Our data represent a comprehensive resource for further investigations on the role of the gut microbiome in promoting or preventing ACVD as well as other related diseases.The gut microbiota may play a role in cardiovascular diseases. Here, the authors perform a metagenome-wide association study on stools from individuals with atherosclerotic cardiovascular disease and healthy controls, identifying microbial strains and functions associated with the disease.}, } @article {pmid29018121, year = {2017}, author = {Hooks, KB and O'Malley, MA}, title = {Dysbiosis and Its Discontents.}, journal = {mBio}, volume = {8}, number = {5}, pages = {}, doi = {10.1128/mBio.01492-17}, pmid = {29018121}, issn = {2150-7511}, mesh = {Biodiversity ; *Dysbiosis ; Homeostasis ; Humans ; *Microbiota ; }, abstract = {Dysbiosis is a key term in human microbiome research, especially when microbiome patterns are associated with disease states. Although some questions have been raised about how this term is applied, its use continues undiminished in the literature. We investigate the ways in which microbiome researchers discuss dysbiosis and then assess the impact of different concepts of dysbiosis on microbiome research. After an overview of the term's historical roots, we conduct quantitative and qualitative analyses of a large selection of contemporary dysbiosis statements. We categorize both short definitions and longer conceptual statements about dysbiosis. Further analysis allows us to identify the problematic implications of how dysbiosis is used, particularly with regard to causal hypotheses and normal-abnormal distinctions. We suggest that researchers should reflect carefully on the ways in which they discuss dysbiosis, in order for the field to continue to develop greater predictive scope and explanatory depth.}, } @article {pmid28988258, year = {2017}, author = {Wagner Mackenzie, B and Waite, DW and Hoggard, M and Taylor, MW and Biswas, K and Douglas, RG}, title = {Moving beyond descriptions of diversity: clinical and research implications of bacterial imbalance in chronic rhinosinusitis.}, journal = {Rhinology}, volume = {55}, number = {4}, pages = {291-297}, doi = {10.4193/Rhin17.135}, pmid = {28988258}, issn = {0300-0729}, mesh = {Bacterial Physiological Phenomena ; Chronic Disease ; Discriminant Analysis ; Ecosystem ; Humans ; Machine Learning ; *Microbiota ; Paranasal Sinuses/*microbiology ; Rhinitis/*microbiology/therapy ; Sinusitis/*microbiology/therapy ; }, abstract = {Chronic rhinosinusitis (CRS) is a debilitating disease which affects 5-16% of the general population and involves long-term inflammation of the sinonasal cavity. While microbial involvement in the pathogenesis of CRS has long been suspected, the exact role of microbes remains unclear. Recent application of cultivation-independent, molecular methods has provided much new information, taking advantage of developments in both laboratory- and bioinformatics-based analyses. The aim of this mini-review is to present a variety of available bioinformatics approaches, such as data classification techniques and network analyses, with proven applications in other aspects of human microbiome health and disease research. The uses of molecular techniques in the clinical setting are still in its infancy, but these tools can further our understanding of microbial imbalance during chronic disease and help guide effective patient treatment. The mini-review emphasises ways in which CRS bacterial gene-targeted sequencing data can progress beyond descriptive summaries and toward unlocking the mechanisms by which bacterial communities can be markers for sinus health.}, } @article {pmid28987073, year = {2017}, author = {Ejtahed, HS and Hasani-Ranjbar, S and Larijani, B}, title = {Human Microbiome as an Approach to Personalized Medicine.}, journal = {Alternative therapies in health and medicine}, volume = {23}, number = {6}, pages = {8-9}, pmid = {28987073}, issn = {1078-6791}, mesh = {Biodiversity ; Humans ; Microbiology/trends ; *Microbiota ; Pharmacogenetics/*trends ; Precision Medicine/*trends ; }, abstract = {Personalized medicine is an approach for medical decisions, practices, and interventions that considers individual variations in genes, environment, and lifestyle for each person. Regarding complex metabolic patterns associated with different diseases, characterizing unique metabolic patterns of each patient seems like a practical approach. We can imagine a future in which routinely analyzing the microbiome allows us to predict individualized responses to different foods and drugs. Microbiome analysis of individuals may be added to future routine personalized medicine protocols after comparing the costs and benefits of microbiome-sequencing technology. Moreover, improved understanding of the human microbiome could lead to the development of novel therapeutic strategies for different diseases. Potential therapeutic agents, such as personalized probiotic and prebiotic supplements, dietary interventions, and fecal microbiota transplantation that can be used to reshape the gut microbiome, represent a reasonable strategy in an era of personalized medicine.}, } @article {pmid28986319, year = {2017}, author = {Broeckx, G and Vandenheuvel, D and Henkens, T and Kiekens, S and van den Broek, MFL and Lebeer, S and Kiekens, F}, title = {Enhancing the viability of Lactobacillus rhamnosus GG after spray drying and during storage.}, journal = {International journal of pharmaceutics}, volume = {534}, number = {1-2}, pages = {35-41}, doi = {10.1016/j.ijpharm.2017.09.075}, pmid = {28986319}, issn = {1873-3476}, mesh = {Colony Count, Microbial/methods ; Desiccation/methods ; Drug Storage/methods ; Excipients/chemistry ; Freeze Drying/methods ; Hot Temperature ; Humans ; Lactobacillus rhamnosus/*chemistry ; Lactose/chemistry ; Microbial Viability/*drug effects ; Microbiota/physiology ; Powders/chemistry ; Probiotics/chemistry ; Protective Agents/chemistry ; Survival Rate ; Transition Temperature ; Trehalose/chemistry ; }, abstract = {Increasing knowledge about the human microbiome has led to a growing awareness of the potential of applying probiotics to improve our health. The pharmaceutical industry shows an emerging interest in pharmaceutical formulations containing these beneficial microbes, the so-called pharmabiotics. An important manufacturing step is the drying of the probiotics, as this can increase the stability and shelf life of the finished pharmabiotic product. Unfortunately, drying also puts stress on microbial cells, thus causing a decrease in viability. We aimed to examine the effect of different drying media and protective excipients on the viability of the prototype probiotic strain Lactobacillus rhamnosus GG after spray drying and during subsequent storage for 28 weeks. The presence of phosphates in the drying medium showed to have a superior protective effect, especially during long-term storage at room temperature. Addition of lactose or trehalose resulted in significantly improved survival rates after drying as well as during long-term storage for the tested excipients. Both disaccharides are characterized by a high glass transition temperature. Maltodextrin showed less protective capacities compared to lactose and trehalose in all tested conditions. The usage of mannitol or dextran resulted in sticky powders and low yields, so further testing was not possible. In addition to optimizing the viability, future research will also explore the functionality of cellular probiotic components after spray drying in order to safeguard the probiotic activity of the formulated pharmabiotics.}, } @article {pmid28980268, year = {2017}, author = {Zhu, X and Wang, J and Reyes-Gibby, C and Shete, S}, title = {Processing and Analyzing Human Microbiome Data.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {1666}, number = {}, pages = {649-677}, doi = {10.1007/978-1-4939-7274-6_31}, pmid = {28980268}, issn = {1940-6029}, mesh = {Adenocarcinoma/microbiology ; Bacteria/genetics ; Esophageal Neoplasms/microbiology ; High-Throughput Nucleotide Sequencing/*methods ; Humans ; *Microbiota ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, RNA/methods ; *Software ; }, abstract = {The human microbiome is associated with complex disorders such as diabetes, cancer, obesity and cardiovascular disorders. Recent technological developments have allowed researchers to fully quantify the composition of the microbiome using culture-independent approaches, resulting in a large amount of microbiome data, which provide invaluable opportunities to assess the important contributions of the microbiome to human health and disease. In this chapter, we discuss and evaluate multiple statistical approaches for processing, summarizing, and analyzing microbiome data. Specifically, we provide programming scripts for processing microbiome data using QIIME and calculating alpha and beta diversities, assessing the association between diversities and outcomes of interest using R programs, as well as interpretation of results. We illustrate the methods in the context of analyzing the foregut microbiome in esophageal adenocarcinoma.}, } @article {pmid28971865, year = {2017}, author = {Healey, KR and Nagasaki, Y and Zimmerman, M and Kordalewska, M and Park, S and Zhao, Y and Perlin, DS}, title = {The Gastrointestinal Tract Is a Major Source of Echinocandin Drug Resistance in a Murine Model of Candida glabrata Colonization and Systemic Dissemination.}, journal = {Antimicrobial agents and chemotherapy}, volume = {61}, number = {12}, pages = {}, doi = {10.1128/AAC.01412-17}, pmid = {28971865}, issn = {1098-6596}, mesh = {Aminoglycosides/pharmacology ; Animals ; Antifungal Agents/pharmacokinetics/*pharmacology ; Candida glabrata/*drug effects/genetics/growth & development ; Candidiasis/*drug therapy/immunology/microbiology ; Chitin Synthase/antagonists & inhibitors/genetics/metabolism ; Dexamethasone/adverse effects ; Disease Models, Animal ; Drug Administration Schedule ; Drug Resistance, Fungal/genetics ; Drug Tolerance/genetics ; Echinocandins/pharmacokinetics/*pharmacology ; Female ; Fungal Proteins/*genetics/metabolism ; Gastrointestinal Tract/*drug effects/immunology/microbiology ; Glucosyltransferases/*genetics/metabolism ; Humans ; Immunosuppressive Agents/adverse effects ; Isoenzymes/genetics/metabolism ; Lipopeptides/pharmacokinetics/*pharmacology ; Mice ; Microbial Sensitivity Tests ; Mutation ; }, abstract = {Candida species are a part of the human microbiome and can cause systemic infection upon immune suppression. Candida glabrata infections are increasing and have greater rates of antifungal resistance than other species. Here, we present a C. glabrata gastrointestinal (GI) colonization model to explore whether colonized yeast exposed to caspofungin, an echinocandin antifungal, develop characteristic resistance mutations and, upon immunosuppression, breakthrough causing systemic infection. Daily therapeutic dosing (5 mg/kg of body weight) of caspofungin resulted in no reduction in fecal burdens, organ breakthrough rates similar to control groups, and resistance rates (0 to 10%) similar to those reported clinically. Treatment with 20 mg/kg caspofungin initially reduced burdens, but a rebound following 5 to 9 days of treatment was accompanied by high levels of resistance (FKS1/FKS2 mutants). Although breakthrough rates decreased in this group, the same FKS mutants were recovered from organs. In an attempt to negate drug tolerance that is critical for resistance development, we cotreated mice with daily caspofungin and the chitin synthase inhibitor nikkomycin Z. The largest reduction (3 log) in GI burdens was obtained within 3 to 5 days of 20 mg/kg caspofungin plus nikkomycin treatment. Yet, echinocandin resistance, characterized by a novel Fks1-L630R substitution, was identified following 5 to 7 days of treatment. Therapeutic caspofungin plus nikkomycin treatment left GI burdens unchanged but significantly reduced organ breakthrough rates (20%; P < 0.05). Single-dose pharmacokinetics demonstrated low levels of drug penetration into the GI lumen posttreatment with caspofungin. Overall, we show that C. glabrata echinocandin resistance can arise within the GI tract and that resistant mutants can readily disseminate upon immunosuppression.}, } @article {pmid28968799, year = {2018}, author = {Äijö, T and Müller, CL and Bonneau, R}, title = {Temporal probabilistic modeling of bacterial compositions derived from 16S rRNA sequencing.}, journal = {Bioinformatics (Oxford, England)}, volume = {34}, number = {3}, pages = {372-380}, doi = {10.1093/bioinformatics/btx549}, pmid = {28968799}, issn = {1367-4811}, abstract = {Motivation: The number of microbial and metagenomic studies has increased drastically due to advancements in next-generation sequencing-based measurement techniques. Statistical analysis and the validity of conclusions drawn from (time series) 16S rRNA and other metagenomic sequencing data is hampered by the presence of significant amount of noise and missing data (sampling zeros). Accounting uncertainty in microbiome data is often challenging due to the difficulty of obtaining biological replicates. Additionally, the compositional nature of current amplicon and metagenomic data differs from many other biological data types adding another challenge to the data analysis.

Results: To address these challenges in human microbiome research, we introduce a novel probabilistic approach to explicitly model overdispersion and sampling zeros by considering the temporal correlation between nearby time points using Gaussian Processes. The proposed Temporal Gaussian Process Model for Compositional Data Analysis (TGP-CODA) shows superior modeling performance compared to commonly used Dirichlet-multinomial, multinomial and non-parametric regression models on real and synthetic data. We demonstrate that the nonreplicative nature of human gut microbiota studies can be partially overcome by our method with proper experimental design of dense temporal sampling. We also show that different modeling approaches have a strong impact on ecological interpretation of the data, such as stationarity, persistence and environmental noise models.

A Stan implementation of the proposed method is available under MIT license at https://github.com/tare/GPMicrobiome.

Contact: taijo@flatironinstitute.org or rb113@nyu.edu.

Supplementary information: Supplementary data are available at Bioinformatics online.}, } @article {pmid28968702, year = {2017}, author = {Hawinkel, S and Mattiello, F and Bijnens, L and Thas, O}, title = {A broken promise: microbiome differential abundance methods do not control the false discovery rate.}, journal = {Briefings in bioinformatics}, volume = {}, number = {}, pages = {}, doi = {10.1093/bib/bbx104}, pmid = {28968702}, issn = {1477-4054}, abstract = {High-throughput sequencing technologies allow easy characterization of the human microbiome, but the statistical methods to analyze microbiome data are still in their infancy. Differential abundance methods aim at detecting associations between the abundances of bacterial species and subject grouping factors. The results of such methods are important to identify the microbiome as a prognostic or diagnostic biomarker or to demonstrate efficacy of prodrug or antibiotic drugs. Because of a lack of benchmarking studies in the microbiome field, no consensus exists on the performance of the statistical methods. We have compared a large number of popular methods through extensive parametric and nonparametric simulation as well as real data shuffling algorithms. The results are consistent over the different approaches and all point to an alarming excess of false discoveries. This raises great doubts about the reliability of discoveries in past studies and imperils reproducibility of microbiome experiments. To further improve method benchmarking, we introduce a new simulation tool that allows to generate correlated count data following any univariate count distribution; the correlation structure may be inferred from real data. Most simulation studies discard the correlation between species, but our results indicate that this correlation can negatively affect the performance of statistical methods.}, } @article {pmid28968189, year = {2018}, author = {Vázquez-Baeza, Y and Callewaert, C and Debelius, J and Hyde, E and Marotz, C and Morton, JT and Swafford, A and Vrbanac, A and Dorrestein, PC and Knight, R}, title = {Impacts of the Human Gut Microbiome on Therapeutics.}, journal = {Annual review of pharmacology and toxicology}, volume = {58}, number = {}, pages = {253-270}, doi = {10.1146/annurev-pharmtox-042017-031849}, pmid = {28968189}, issn = {1545-4304}, abstract = {The human microbiome contains a vast source of genetic and biochemical variation, and its impacts on therapeutic responses are just beginning to be understood. This expanded understanding is especially important because the human microbiome differs far more among different people than does the human genome, and it is also dramatically easier to change. Here, we describe some of the major factors driving differences in the human microbiome among individuals and populations. We then describe some of the many ways in which gut microbes modify the action of specific chemotherapeutic agents, including nonsteroidal anti-inflammatory drugs and cardiac glycosides, and outline the potential of fecal microbiota transplant as a therapeutic. Intriguingly, microbes also alter how hosts respond to therapeutic agents through various pathways acting at distal sites. Finally, we discuss some of the computational and practical issues surrounding use of the microbiome to stratify individuals for drug response, and we envision a future where the microbiome will be modified to increase everyone's potential to benefit from therapy.}, } @article {pmid28967885, year = {2017}, author = {Sinha, R and Abu-Ali, G and Vogtmann, E and Fodor, AA and Ren, B and Amir, A and Schwager, E and Crabtree, J and Ma, S and , and Abnet, CC and Knight, R and White, O and Huttenhower, C}, title = {Assessment of variation in microbial community amplicon sequencing by the Microbiome Quality Control (MBQC) project consortium.}, journal = {Nature biotechnology}, volume = {35}, number = {11}, pages = {1077-1086}, doi = {10.1038/nbt.3981}, pmid = {28967885}, issn = {1546-1696}, support = {P30 DK043351/DK/NIDDK NIH HHS/United States ; U01 HG006537/HG/NHGRI NIH HHS/United States ; U01 HG004866/HG/NHGRI NIH HHS/United States ; U54 DE023798/DE/NIDCR NIH HHS/United States ; R01 HG005220/HG/NHGRI NIH HHS/United States ; R01 HG004872/HG/NHGRI NIH HHS/United States ; R01 HG005969/HG/NHGRI NIH HHS/United States ; R01 CA179243/CA/NCI NIH HHS/United States ; }, mesh = {Bacteria/*genetics ; DNA, Bacterial/*chemistry/*genetics ; Gastrointestinal Microbiome/*genetics ; Humans ; *Microbiota ; Nucleic Acid Amplification Techniques/*methods/*standards ; Reference Standards ; Research Design ; }, abstract = {In order for human microbiome studies to translate into actionable outcomes for health, meta-analysis of reproducible data from population-scale cohorts is needed. Achieving sufficient reproducibility in microbiome research has proven challenging. We report a baseline investigation of variability in taxonomic profiling for the Microbiome Quality Control (MBQC) project baseline study (MBQC-base). Blinded specimen sets from human stool, chemostats, and artificial microbial communities were sequenced by 15 laboratories and analyzed using nine bioinformatics protocols. Variability depended most on biospecimen type and origin, followed by DNA extraction, sample handling environment, and bioinformatics. Analysis of artificial community specimens revealed differences in extraction efficiency and bioinformatic classification. These results may guide researchers in experimental design choices for gut microbiome studies.}, } @article {pmid28963010, year = {2017}, author = {Coutinho, CMLM and Coutinho-Silva, R and Zinkevich, V and Pearce, CB and Ojcius, DM and Beech, I}, title = {Sulphate-reducing bacteria from ulcerative colitis patients induce apoptosis of gastrointestinal epithelial cells.}, journal = {Microbial pathogenesis}, volume = {112}, number = {}, pages = {126-134}, doi = {10.1016/j.micpath.2017.09.054}, pmid = {28963010}, issn = {1096-1208}, mesh = {Apoptosis/*drug effects ; Bacteria/*drug effects ; Biopsy ; Cell Line ; Coculture Techniques ; Colitis, Ulcerative/*microbiology ; Colon/pathology ; Colonoscopy ; Desulfovibrio/metabolism ; Epithelial Cells/*metabolism/pathology ; Escherichia coli/isolation & purification/metabolism ; Feces/microbiology ; Gastrointestinal Tract/*metabolism ; Humans ; Inflammatory Bowel Diseases/microbiology ; Intestinal Mucosa/microbiology/pathology ; Sulfates/*pharmacology ; United Kingdom ; }, abstract = {The human microbiome consists of a multitude of bacterial genera and species which continuously interact with one another and their host establishing a metabolic equilibrium. The dysbiosis can lead to the development of pathology, such as inflammatory bowel diseases. Sulfide-producing prokaryotes, including sulphate-reducing bacteria (SRB) constituting different genera, including the Desulfovibrio, are commonly detected within the human microbiome recovered from fecal material or colonic biopsy samples. It has been proposed that SRB likely contribute to colonic pathology, for example ulcerative colitis (UC). The interaction of SRB with the human colon and intestinal epithelial cell lines has been investigated using Desulfovibrio indonesiensis as a model mono-culture and in a co-culture with E. coli isolate, and with SRB consortia from human biopsy samples. We find that D. indonesiensis, whether as a mono- or co-culture, was internalized and induced apoptosis in colon epithelial cells. This effect was enhanced in the presence of E. coli. The SRB combination obtained through enrichment of biopsies from UC patients induced apoptosis of a human intestinal epithelial cell line. This response was not observed in SRB enrichments from healthy (non-UC) controls. Importantly, apoptosis was detected in epithelial cells from UC patients and was not seen in epithelial cells of healthy donors. Furthermore, the antibody raised against exopolysaccharides (EPS) of D. indonesiensis cross reacted with the SRB population from UC patients but not with the SRB combination from non-UC controls. This study reinforces a correlation between the presence of sulphate-reducing bacteria and an inflammatory response in UC sufferers.}, } @article {pmid28961122, year = {2017}, author = {Ma, Y and Hu, X and He, T and Jiang, X}, title = {Clustering and Integrating of Heterogeneous Microbiome Data by Joint Symmetric Nonnegative Matrix Factorization with Laplacian Regularization.}, journal = {IEEE/ACM transactions on computational biology and bioinformatics}, volume = {}, number = {}, pages = {}, doi = {10.1109/TCBB.2017.2756628}, pmid = {28961122}, issn = {1557-9964}, abstract = {Many datasets existed in the real world are often comprised of different representations or views which provide complementary information to each other. To integrate information from multiple views, data integration approaches such as nonnegative matrix factorization (NMF) have been developed to combine multiple heterogeneous data simultaneously to obtain a comprehensive representation. In this paper, we proposed a novel variant of symmetric nonnegative matrix factorization (SNMF), called Laplacian regularization based joint symmetric nonnegative matrix factorization (LJ-SNMF) for clustering multi-view data. We conduct extensive experiments on several realistic datasets including Human Microbiome Project data. The experimental results show that the proposed method outperforms other variants of NMF, which suggests the potential application of LJ-SNMF in clustering multi-view datasets. Additionally, we also demonstrate the capability of LJ-SNMF in community finding.}, } @article {pmid28959368, year = {2017}, author = {Chen, EZ and Bushman, FD and Li, H}, title = {A Model-Based Approach For Species Abundance Quantification Based On Shotgun Metagenomic Data.}, journal = {Statistics in biosciences}, volume = {9}, number = {1}, pages = {13-27}, doi = {10.1007/s12561-016-9148-x}, pmid = {28959368}, issn = {1867-1764}, support = {R01 CA127334/CA/NCI NIH HHS/United States ; R01 GM097505/GM/NIGMS NIH HHS/United States ; }, abstract = {The human microbiome, which includes the collective microbes residing in or on the human body, has a profound influence on the human health. DNA sequencing technology has made the large-scale human microbiome studies possible by using shotgun metagenomic sequencing. One important aspect of data analysis of such metagenomic data is to quantify the bacterial abundances based on the metagenomic sequencing data. Existing methods almost always quantify such abundances one sample at a time, which ignore certain systematic differences in read coverage along the genomes due to GC contents, copy number variation and the bacterial origin of replication. In order to account for such differences in read counts, we propose a multi-sample Poisson model to quantify microbial abundances based on read counts that are assigned to species-specific taxonomic markers. Our model takes into account the marker-specific effects when normalizing the sequencing count data in order to obtain more accurate quantification of the species abundances. Compared to currently available methods on simulated data and real data sets, our method has demonstrated an improved accuracy in bacterial abundance quantification, which leads to more biologically interesting results from downstream data analysis.}, } @article {pmid28954525, year = {2018}, author = {Chung, SY and Ravel, J and Regan, M}, title = {Clinical Relevance of Gastrointestinal Microbiota During Pregnancy: A Primer for Nurses.}, journal = {Biological research for nursing}, volume = {20}, number = {1}, pages = {84-102}, doi = {10.1177/1099800417732412}, pmid = {28954525}, issn = {1552-4175}, support = {R01 NR014826/NR/NINR NIH HHS/United States ; }, mesh = {Adult ; Female ; Gastrointestinal Microbiome/*physiology ; Gastrointestinal Tract/*microbiology ; Humans ; Infant, Newborn ; Pregnancy ; Pregnancy Outcome ; }, abstract = {Emerging evidence about the human microbiome, a collective term for all the microorganisms living in and on the human body, consistently demonstrates the critical influence it has on host physiology and disease risk. The microbiota in the gastrointestinal (GI) tract has the most significant and far-reaching effect on human physiology. The maternal GI microbiota can decrease the risk of adverse pregnancy outcomes by modulating energy extraction, glucose metabolism, vitamin production, and host immunity essential for optimal maternal and neonatal health. Moreover, the maternal GI microbiota is thought to influence colonization of the fetus and neonate that may predispose them to different health trajectories. This article provides a basic understanding about the influence of the structure of the maternal GI microbiota, the fundamental role it plays during pregnancy, and the factors that influence the structure, and subsequently function, of the GI microbiota in the general and pregnant population. While only a small number of studies have examined this topic during pregnancy, the preponderance of the evidence supports the need to clarify baseline structure and function of GI microbiota and its associations with pregnancy outcomes. In addition, the results from the studies conducted in the general population can be extrapolated to pregnancy in many cases. This knowledge is essential for clinicians who need to understand the implications of the microbiota for disease and wellness in order to address the care factors that may adversely influence the GI microbiota during pregnancy.}, } @article {pmid28953883, year = {2017}, author = {Lloyd-Price, J and Mahurkar, A and Rahnavard, G and Crabtree, J and Orvis, J and Hall, AB and Brady, A and Creasy, HH and McCracken, C and Giglio, MG and McDonald, D and Franzosa, EA and Knight, R and White, O and Huttenhower, C}, title = {Strains, functions and dynamics in the expanded Human Microbiome Project.}, journal = {Nature}, volume = {550}, number = {7674}, pages = {61-66}, doi = {10.1038/nature23889}, pmid = {28953883}, issn = {1476-4687}, support = {U54 HG004973/HG/NHGRI NIH HHS/United States ; U54 DK102557/DK/NIDDK NIH HHS/United States ; P30 DK043351/DK/NIDDK NIH HHS/United States ; U01 HG006537/HG/NHGRI NIH HHS/United States ; U54 AI084844/AI/NIAID NIH HHS/United States ; U01 HG004866/HG/NHGRI NIH HHS/United States ; U54 HG004968/HG/NHGRI NIH HHS/United States ; R01 HG004872/HG/NHGRI NIH HHS/United States ; U54 HG003079/HG/NHGRI NIH HHS/United States ; U54 HG004969/HG/NHGRI NIH HHS/United States ; }, mesh = {Datasets as Topic ; Humans ; Metagenome/genetics/physiology ; Microbiota/genetics/*physiology ; Molecular Sequence Annotation ; National Institutes of Health (U.S.) ; Organ Specificity ; *Phylogeny ; Spatio-Temporal Analysis ; Time Factors ; United States ; }, abstract = {The characterization of baseline microbial and functional diversity in the human microbiome has enabled studies of microbiome-related disease, diversity, biogeography, and molecular function. The National Institutes of Health Human Microbiome Project has provided one of the broadest such characterizations so far. Here we introduce a second wave of data from the study, comprising 1,631 new metagenomes (2,355 total) targeting diverse body sites with multiple time points in 265 individuals. We applied updated profiling and assembly methods to provide new characterizations of microbiome personalization. Strain identification revealed subspecies clades specific to body sites; it also quantified species with phylogenetic diversity under-represented in isolate genomes. Body-wide functional profiling classified pathways into universal, human-enriched, and body site-enriched subsets. Finally, temporal analysis decomposed microbial variation into rapidly variable, moderately variable, and stable subsets. This study furthers our knowledge of baseline human microbial diversity and enables an understanding of personalized microbiome function and dynamics.}, } @article {pmid28952002, year = {2017}, author = {Leng, J and Peruluswami, P and Bari, S and Gaur, S and Radparvar, F and Parvez, F and Chen, Y and Flores, C and Gany, F}, title = {South Asian Health: Inflammation, Infection, Exposure, and the Human Microbiome.}, journal = {Journal of immigrant and minority health}, volume = {}, number = {}, pages = {}, doi = {10.1007/s10903-017-0652-y}, pmid = {28952002}, issn = {1557-1920}, support = {U54 CA137788/CA/NCI NIH HHS/United States ; R13 MD007147/MD/NIMHD NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; R13 MD007147-01A1//National Institute on Minority Health and Health Disparities/ ; P30CA008748//National Cancer Institute/ ; }, abstract = {This paper presents the results of the literature review conducted for the working group topic on inflammation, infection, exposure, and the human microbiome. Infection and chronic inflammation can elevate risk for cardiovascular disease and cancer. Environmental exposures common among South Asian (SA) subgroups, such as arsenic exposure among Bangladeshis and particulate matter air pollution among taxi drivers, also pose risks. This review explores the effects of exposure to arsenic and particulate matter, as well as other infections common among SAs, including human papillomavirus (HPV) and hepatitis B/C infection. Emerging research on the human microbiome, and the effect of microbiome changes on obesity and diabetes risk among SAs are also explored.}, } @article {pmid28945201, year = {2017}, author = {Ohlemacher, SI and Giblin, DE and d'Avignon, DA and Stapleton, AE and Trautner, BW and Henderson, JP}, title = {Enterobacteria secrete an inhibitor of Pseudomonas virulence during clinical bacteriuria.}, journal = {The Journal of clinical investigation}, volume = {127}, number = {11}, pages = {4018-4030}, doi = {10.1172/JCI92464}, pmid = {28945201}, issn = {1558-8238}, support = {P30 DK089507/DK/NIDDK NIH HHS/United States ; R01 DK088830/DK/NIDDK NIH HHS/United States ; P50 DK064540/DK/NIDDK NIH HHS/United States ; R01 DK099534/DK/NIDDK NIH HHS/United States ; P41 GM103422/GM/NIGMS NIH HHS/United States ; R21 DK092293/DK/NIDDK NIH HHS/United States ; T32 AI007172/AI/NIAID NIH HHS/United States ; UL1 TR000448/TR/NCATS NIH HHS/United States ; P41 RR000954/RR/NCRR NIH HHS/United States ; R56 DK111930/DK/NIDDK NIH HHS/United States ; U54 CK000482/CK/NCEZID CDC HHS/United States ; UL1 TR002345/TR/NCATS NIH HHS/United States ; }, mesh = {Antibiosis ; Bacteriuria/*microbiology ; Biosynthetic Pathways ; Escherichia coli Infections/metabolism/*microbiology ; Escherichia coli Proteins/physiology ; Humans ; Iron/metabolism ; Models, Molecular ; Molecular Conformation ; Pseudomonas aeruginosa/metabolism/*pathogenicity ; Siderophores/chemistry/metabolism/*secretion ; Urinary Tract Infections/metabolism/*microbiology ; Uropathogenic Escherichia coli/*physiology ; Virulence ; }, abstract = {Escherichia coli and other Enterobacteriaceae are among the most common pathogens of the human urinary tract. Among the genetic gains of function associated with urinary E. coli isolates is the Yersinia high pathogenicity island (HPI), which directs the biosynthesis of yersiniabactin (Ybt), a virulence-associated metallophore. Using a metabolomics approach, we found that E. coli and other Enterobacteriaceae expressing the Yersinia HPI also secrete escherichelin, a second metallophore whose chemical structure matches a known synthetic inhibitor of the virulence-associated pyochelin siderophore system in Pseudomonas aeruginosa. We detected escherichelin during clinical E. coli urinary tract infection (UTI) and experimental human colonization with a commensal, potentially probiotic E. coli bacteriuria strain. Escherichelin production by colonizing enterobacteria may help human hosts resist opportunistic infections by Pseudomonas and other pyochelin-expressing bacteria. This siderophore-based mechanism of microbial antagonism may be one of many elements contributing to the protective effects of the human microbiome. Future UTI-preventive probiotic strains may benefit by retaining the escherichelin biosynthetic capacity of the Yersinia HPI while eliminating the Ybt biosynthetic capacity.}, } @article {pmid28943872, year = {2017}, author = {Hidalgo-Cantabrana, C and Moro-García, MA and Blanco-Míguez, A and Fdez-Riverola, F and Lourenço, A and Alonso-Arias, R and Sánchez, B}, title = {In Silico Screening of the Human Gut Metaproteome Identifies Th17-Promoting Peptides Encrypted in Proteins of Commensal Bacteria.}, journal = {Frontiers in microbiology}, volume = {8}, number = {}, pages = {1726}, doi = {10.3389/fmicb.2017.01726}, pmid = {28943872}, issn = {1664-302X}, abstract = {Scientific studies focused on the role of the human microbiome over human health have generated billions of gigabits of genetic information during the last decade. Nowadays integration of all this information in public databases and development of pipelines allowing us to biotechnologically exploit this information are urgently needed. Prediction of the potential bioactivity of the products encoded by the human gut microbiome, or metaproteome, is the first step for identifying proteins responsible for the molecular interaction between microorganisms and the immune system. We have recently published the Mechanism of Action of the Human Microbiome (MAHMI) database (http://www.mahmi.org), conceived as a resource compiling peptide sequences with a potential immunomodulatory activity. Fifteen out of the 300 hundred million peptides contained in the MAHMI database were synthesized. These peptides were identified as being encrypted in proteins produced by gut microbiota members, they do not contain cleavage points for the major intestinal endoproteases and displayed high probability to have immunomodulatory bioactivity. The bacterial peptides FR-16 and LR-17 encrypted in proteins from Bifidobacterium longum DJ010A and Bifidobacterium fragilis YCH46 respectively, showed the higher immune modulation capability over human peripheral blood mononuclear cells. Both peptides modulated the immune response toward increases in the Th17 and decreases in the Th1 cell response, together with an induction of IL-22 production. These results strongly suggest the combined use of bioinformatics and in vitro tools as a first stage in the screening of bioactive peptides encrypted in the human gut metaproteome.}, } @article {pmid28938903, year = {2017}, author = {O'Hara, NB and Reed, HJ and Afshinnekoo, E and Harvin, D and Caplan, N and Rosen, G and Frye, B and Woloszynek, S and Ounit, R and Levy, S and Butler, E and Mason, CE}, title = {Metagenomic characterization of ambulances across the USA.}, journal = {Microbiome}, volume = {5}, number = {1}, pages = {125}, doi = {10.1186/s40168-017-0339-6}, pmid = {28938903}, issn = {2049-2618}, support = {R01 AI125416/AI/NIAID NIH HHS/United States ; }, mesh = {*Ambulances ; Bacteria/classification/genetics/*isolation & purification/pathogenicity ; Cross Infection/microbiology ; Genome, Bacterial ; High-Throughput Nucleotide Sequencing ; Hospitals ; Humans ; *Metagenome ; *Metagenomics ; *Microbial Consortia/genetics ; *Microbiota/genetics ; United States ; }, abstract = {BACKGROUND: Microbial communities in our built environments have great influence on human health and disease. A variety of built environments have been characterized using a metagenomics-based approach, including some healthcare settings. However, there has been no study to date that has used this approach in pre-hospital settings, such as ambulances, an important first point-of-contact between patients and hospitals.

RESULTS: We sequenced 398 samples from 137 ambulances across the USA using shotgun sequencing. We analyzed these data to explore the microbial ecology of ambulances including characterizing microbial community composition, nosocomial pathogens, patterns of diversity, presence of functional pathways and antimicrobial resistance, and potential spatial and environmental factors that may contribute to community composition. We found that the top 10 most abundant species are either common built environment microbes, microbes associated with the human microbiome (e.g., skin), or are species associated with nosocomial infections. We also found widespread evidence of antimicrobial resistance markers (hits ~ 90% samples). We identified six factors that may influence the microbial ecology of ambulances including ambulance surfaces, geographical-related factors (including region, longitude, and latitude), and weather-related factors (including temperature and precipitation).

CONCLUSIONS: While the vast majority of microbial species classified were beneficial, we also found widespread evidence of species associated with nosocomial infections and antimicrobial resistance markers. This study indicates that metagenomics may be useful to characterize the microbial ecology of pre-hospital ambulance settings and that more rigorous testing and cleaning of ambulances may be warranted.}, } @article {pmid28915922, year = {2017}, author = {Winglee, K and Howard, AG and Sha, W and Gharaibeh, RZ and Liu, J and Jin, D and Fodor, AA and Gordon-Larsen, P}, title = {Recent urbanization in China is correlated with a Westernized microbiome encoding increased virulence and antibiotic resistance genes.}, journal = {Microbiome}, volume = {5}, number = {1}, pages = {121}, doi = {10.1186/s40168-017-0338-7}, pmid = {28915922}, issn = {2049-2618}, support = {UL1 TR001111/TR/NCATS NIH HHS/United States ; P30 ES010126/ES/NIEHS NIH HHS/United States ; R01 DK104371/DK/NIDDK NIH HHS/United States ; R01 HL108427/HL/NHLBI NIH HHS/United States ; R24 HD050924/HD/NICHD NIH HHS/United States ; }, mesh = {Aged ; Bacteria/*genetics/pathogenicity ; China ; *Diet, Western ; Drug Resistance, Microbial/*genetics ; Escherichia coli/genetics/pathogenicity ; Feeding Behavior ; Female ; *Gastrointestinal Microbiome/genetics ; Genetic Variation ; High-Throughput Nucleotide Sequencing ; Humans ; Male ; *Metabolome ; Metagenomics ; Middle Aged ; Shigella/genetics/pathogenicity ; *Urbanization ; Virulence/genetics ; }, abstract = {BACKGROUND: Urbanization is associated with an increased risk for a number of diseases, including obesity, diabetes, and cancer, which all also show associations with the microbiome. While microbial community composition has been shown to vary across continents and in traditional versus Westernized societies, few studies have examined urban-rural differences in neighboring communities within a single country undergoing rapid urbanization. In this study, we compared the gut microbiome, plasma metabolome, dietary habits, and health biomarkers of rural and urban people from a single Chinese province.

RESULTS: We identified significant differences in the microbiota and microbiota-related plasma metabolites in rural versus recently urban subjects from the Hunan province of China. Microbes with higher relative abundance in Chinese urban samples have been associated with disease in other studies and were substantially more prevalent in the Human Microbiome Project cohort of American subjects. Furthermore, using whole metagenome sequencing, we found that urbanization was associated with a loss of microbial diversity and changes in the relative abundances of Viruses, Archaea, and Bacteria. Gene diversity, however, increased with urbanization, along with the proportion of reads associated with antibiotic resistance and virulence, which were strongly correlated with the presence of Escherichia and Shigella.

CONCLUSIONS: Our data suggest that urbanization has produced convergent evolution of the gut microbial composition in American and urban Chinese populations, resulting in similar compositional patterns of abundant microbes through similar lifestyles on different continents, including a loss of potentially beneficial bacteria and an increase in potentially harmful genes via increased relative abundance of Escherichia and Shigella.}, } @article {pmid28912952, year = {2017}, author = {Pham, TP and Tidjani Alou, M and Traore, SI and Brah, S and Ali Diallo, B and Diallo, A and Sokhna, C and Baptiste, E and Levasseur, A and Fournier, PE and Cadoret, F and Raoult, D}, title = {Noncontiguous finished genome sequences and descriptions of 'Paenibacillus bouchesdurhonensis,' 'Paenibacillus rubinfantis,' 'Paenibacillus senegalimassiliensis' and 'Paenibacillus tuaregi' identified by culturomics.}, journal = {New microbes and new infections}, volume = {20}, number = {}, pages = {1-13}, doi = {10.1016/j.nmni.2017.07.004}, pmid = {28912952}, issn = {2052-2975}, abstract = {Microbial culturomics represents a completely new approach to investigate microbial diversity by using different optimized culture conditions, mass spectrometry, genome sequencing and annotation and phenotypic description that allow for an extensive characterization of new species and the study of the human microbiome. Here we present four new species within the genus Paenibacillus: 'Paenibacillus bouchesdurhonensis' strain Marseille-P3071T, 'Paenibacillus rubinfantis' strain MT18T, 'Paenibacillus senegalimassiliensis' strain SIT18T and 'Paenibacillus tuaregi' strain Marseille-P2472T, which are all facultatively aerobic and Gram-positive bacilli.}, } @article {pmid28912600, year = {2017}, author = {Valencia, PM and Richard, M and Brock, J and Boglioli, E}, title = {The human microbiome: opportunity or hype?.}, journal = {Nature reviews. Drug discovery}, volume = {16}, number = {12}, pages = {823-824}, doi = {10.1038/nrd.2017.154}, pmid = {28912600}, issn = {1474-1784}, } @article {pmid28910638, year = {2017}, author = {Verster, AJ and Ross, BD and Radey, MC and Bao, Y and Goodman, AL and Mougous, JD and Borenstein, E}, title = {The Landscape of Type VI Secretion across Human Gut Microbiomes Reveals Its Role in Community Composition.}, journal = {Cell host & microbe}, volume = {22}, number = {3}, pages = {411-419.e4}, doi = {10.1016/j.chom.2017.08.010}, pmid = {28910638}, issn = {1934-6069}, support = {DP2 AT007802/AT/NCCIH NIH HHS/United States ; R35 GM118159/GM/NIGMS NIH HHS/United States ; UL1 TR001863/TR/NCATS NIH HHS/United States ; //Howard Hughes Medical Institute/United States ; R01 AI080609/AI/NIAID NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Bacteria/classification/genetics/isolation & purification/*metabolism ; Bacterial Proteins/genetics/*metabolism ; Bacteroides/classification/genetics/isolation & purification/metabolism ; Biodiversity ; Female ; *Gastrointestinal Microbiome ; Gastrointestinal Tract/*microbiology ; Humans ; Male ; Middle Aged ; Phylogeny ; Type VI Secretion Systems/genetics/*metabolism ; Young Adult ; }, abstract = {Although gut microbiome composition is well defined, the mechanisms underlying community assembly remain poorly understood. Bacteroidales possess three genetic architectures (GA1-3) of the type VI secretion system (T6SS), an effector delivery pathway that mediates interbacterial competition. Here we define the distribution and role of GA1-3 in the human gut using metagenomic analysis. We find that adult microbiomes harbor limited effector and cognate immunity genes, suggesting selection for compatibility at the species (GA1 and GA2) and strain (GA3) levels. Bacteroides fragilis GA3 is known to mediate potent inter-strain competition, and we observe GA3 enrichment among strains colonizing infant microbiomes, suggesting competition early in life. Additionally, GA3 is associated with increased Bacteroides abundance, indicating that this system confers an advantage in Bacteroides-rich ecosystems. Collectively, these analyses uncover the prevalence of T6SS-dependent competition and reveal its potential role in shaping human gut microbial composition.}, } @article {pmid28910633, year = {2017}, author = {Gomez, A and Espinoza, JL and Harkins, DM and Leong, P and Saffery, R and Bockmann, M and Torralba, M and Kuelbs, C and Kodukula, R and Inman, J and Hughes, T and Craig, JM and Highlander, SK and Jones, MB and Dupont, CL and Nelson, KE}, title = {Host Genetic Control of the Oral Microbiome in Health and Disease.}, journal = {Cell host & microbe}, volume = {22}, number = {3}, pages = {269-278.e3}, doi = {10.1016/j.chom.2017.08.013}, pmid = {28910633}, issn = {1934-6069}, support = {R01 DE019665/DE/NIDCR NIH HHS/United States ; }, mesh = {Age Factors ; Bacteria/classification/genetics/*isolation & purification ; Child ; Child, Preschool ; Dental Caries/*genetics/*microbiology ; Ecosystem ; Female ; Genetic Predisposition to Disease ; Genotype ; Humans ; Male ; *Microbiota ; Mouth/*microbiology ; Phylogeny ; Twins/genetics ; }, abstract = {Host-associated microbial communities are influenced by both host genetics and environmental factors. However, factors controlling the human oral microbiome and their impact on disease remain to be investigated. To determine the combined and relative effects of host genotype and environment on oral microbiome composition and caries phenotypes, we profiled the supragingival plaque microbiome of 485 dizygotic and monozygotic twins aged 5-11. Oral microbiome similarity always increased with shared host genotype, regardless of caries state. Additionally, although most of the variation in the oral microbiome was determined by environmental factors, highly heritable oral taxa were identified. The most heritable oral bacteria were not associated with caries state, did not tend to co-occur with other taxa, and decreased in abundance with age and sugar consumption frequency. Thus, while the human oral microbiome composition is influenced by host genetic background, potentially cariogenic taxa are likely not controlled by genetic factors.}, } @article {pmid28905671, year = {2018}, author = {Prokopienko, AJ and Nolin, TD}, title = {Microbiota-derived uremic retention solutes: perpetrators of altered nonrenal drug clearance in kidney disease.}, journal = {Expert review of clinical pharmacology}, volume = {11}, number = {1}, pages = {71-82}, doi = {10.1080/17512433.2018.1378095}, pmid = {28905671}, issn = {1751-2441}, support = {R01 GM107122/GM/NIGMS NIH HHS/United States ; TL1 TR001858/TR/NCATS NIH HHS/United States ; }, mesh = {Animals ; Cresols/metabolism ; Drug-Related Side Effects and Adverse Reactions/metabolism ; Dysbiosis/complications ; Gastrointestinal Microbiome/*physiology ; Humans ; Indican/metabolism ; Kidney Diseases/*physiopathology ; Liver/enzymology/metabolism ; Pharmaceutical Preparations/metabolism ; Sulfuric Acid Esters/metabolism ; Toxins, Biological/*metabolism ; }, abstract = {INTRODUCTION: Scientific interest in the gut microbiota is increasing due to improved understanding of its implications in human health and disease. In patients with kidney disease, gut microbiota-derived uremic toxins directly contribute to altered nonrenal drug clearance. Microbial imbalances, known as dysbiosis, potentially increase formation of microbiota-derived toxins, and diminished renal clearance leads to toxin accumulation. High concentrations of microbiota-derived toxins such as indoxyl sulfate and p-cresol sulfate perpetrate interactions with drug metabolizing enzymes and transporters, which provides a mechanistic link between increases in drug-related adverse events and dysbiosis in kidney disease. Areas covered: This review summarizes the effects of microbiota-derived uremic toxins on hepatic phase I and phase II drug metabolizing enzymes and drug transporters. Research articles that tested individual toxins were included. Therapeutic strategies to target microbial toxins are also discussed. Expert commentary: Large interindividual variability in toxin concentrations may explain some differences in nonrenal clearance of medications. Advances in human microbiome research provide unique opportunities to systematically evaluate the impact of individual and combined microbial toxins on drug metabolism and transport, and to explore microbiota-derived uremic toxins as potential therapeutic targets.}, } @article {pmid28900019, year = {2017}, author = {Shaw, L and Ribeiro, ALR and Levine, AP and Pontikos, N and Balloux, F and Segal, AW and Roberts, AP and Smith, AM}, title = {The Human Salivary Microbiome Is Shaped by Shared Environment Rather than Genetics: Evidence from a Large Family of Closely Related Individuals.}, journal = {mBio}, volume = {8}, number = {5}, pages = {}, doi = {10.1128/mBio.01237-17}, pmid = {28900019}, issn = {2150-7511}, support = {MR/L000261/1//Medical Research Council/United Kingdom ; }, mesh = {Adult ; Bacteria/genetics ; Cohort Studies ; *Environment ; *Family ; Family Characteristics/ethnology ; Female ; Geography ; Humans ; Male ; *Microbiota/genetics ; Mouth/microbiology ; Polymorphism, Single Nucleotide ; Saliva/*microbiology ; }, abstract = {The human microbiome is affected by multiple factors, including the environment and host genetics. In this study, we analyzed the salivary microbiomes of an extended family of Ashkenazi Jewish individuals living in several cities and investigated associations with both shared household and host genetic similarities. We found that environmental effects dominated over genetic effects. While there was weak evidence of geographical structuring at the level of cities, we observed a large and significant effect of shared household on microbiome composition, supporting the role of the immediate shared environment in dictating the presence or absence of taxa. This effect was also seen when including adults who had grown up in the same household but moved out prior to the time of sampling, suggesting that the establishment of the salivary microbiome earlier in life may affect its long-term composition. We found weak associations between host genetic relatedness and microbiome dissimilarity when using family pedigrees as proxies for genetic similarity. However, this association disappeared when using more-accurate measures of kinship based on genome-wide genetic markers, indicating that the environment rather than host genetics is the dominant factor affecting the composition of the salivary microbiome in closely related individuals. Our results support the concept that there is a consistent core microbiome conserved across global scales but that small-scale effects due to a shared living environment significantly affect microbial community composition.IMPORTANCE Previous research shows that the salivary microbiomes of relatives are more similar than those of nonrelatives, but it remains difficult to distinguish the effects of relatedness and shared household environment. Furthermore, pedigree measures may not accurately measure host genetic similarity. In this study, we include genetic relatedness based on genome-wide single nucleotide polymorphisms (SNPs) (rather than pedigree measures) and shared environment in the same analysis. We quantify the relative importance of these factors by studying the salivary microbiomes in members of a large extended Ashkenazi Jewish family living in different locations. We find that host genetics plays no significant role and that the dominant factor is the shared environment at the household level. We also find that this effect appears to persist in individuals who have moved out of the parental household, suggesting that aspects of salivary microbiome composition established during upbringing can persist over a time scale of years.}, } @article {pmid28899789, year = {2017}, author = {Rózsa, L and Apari, P and Sulyok, M and Tappe, D and Bodó, I and Hardi, R and Müller, V}, title = {The evolutionary logic of sepsis.}, journal = {Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases}, volume = {55}, number = {}, pages = {135-141}, doi = {10.1016/j.meegid.2017.09.006}, pmid = {28899789}, issn = {1567-7257}, mesh = {Animals ; *Biological Evolution ; Disease Susceptibility ; *Host-Pathogen Interactions ; Humans ; Microbiota ; Sepsis/*etiology/transmission ; Virulence ; }, abstract = {The recently proposed Microbiome Mutiny Hypothesis posits that members of the human microbiome obtain information about the host individuals' health status and, when host survival is compromised, switch to an intensive exploitation strategy to maximize residual transmission. In animals and humans, sepsis is an acute systemic reaction to microbes invading the normally sterile body compartments. When induced by formerly mutualistic or neutral microbes, possibly in response to declining host health, sepsis appears to fit the 'microbiome mutiny' scenario except for its apparent failure to enhance transmission of the causative organisms. We propose that the ability of certain species of the microbiome to induce sepsis is not a fortuitous side effect of within-host replication, but rather it might, in some cases, be the result of their adaptive evolution. Whenever host health declines, inducing sepsis can be adaptive for those members of the healthy human microbiome that are capable of colonizing the future cadaver and spread by cadaver-borne transmission. We hypothesize that such microbes might exhibit switches along the 'mutualist - lethal pathogen - decomposer - mutualist again' scenario, implicating a previously unsuspected, surprising level of phenotypic plasticity. This hypothesis predicts that those species of the healthy microbiome that are recurring causative agents of sepsis can participate in the decomposition of cadavers, and can be transmitted as soil-borne or water-borne infections. Furthermore, in individual sepsis cases, the same microbial clones that dominate the systemic infection that precipitates sepsis, should also be present in high concentration during decomposition following death: this prediction is testable by molecular fingerprinting in experimentally induced animal models. Sepsis is a leading cause of human death worldwide. If further research confirms that some cases of sepsis indeed involve the 'mutiny' (facultative phenotypic switching) of normal members of the microbiome, then new strategies could be devised to prevent or treat sepsis by interfering with this process.}, } @article {pmid28887423, year = {2017}, author = {Schmedes, SE and Woerner, AE and Budowle, B}, title = {Forensic human identification using skin microbiomes.}, journal = {Applied and environmental microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1128/AEM.01672-17}, pmid = {28887423}, issn = {1098-5336}, abstract = {The human microbiome contributes significantly to the genetic content of the human body. Genetic and environmental factors help shape the microbiome, and as such, the microbiome can be unique to an individual. Previous studies have demonstrated the potential to use microbiome profiling for forensic applications, however a method has yet to identify stable features of skin microbiomes that produce high classification accuracies for samples collected over reasonably long time intervals. A novel approach is described to classify skin microbiomes to their donors by comparing two features types, Propionibacterium acnes pangenome presence/absence features and nucleotide diversities of stable clade-specific markers. Supervised learning was used to attribute skin microbiomes from 14 skin body sites from 12 healthy individuals sampled at three time points over a >2.5 year period with accuracies up to 100% for three body sites. Feature selection identified a reduced subset of markers from each body site that are highly individualizing, identifying 187 markers from 12 clades. Classification accuracies were compared in a formal model testing framework, and the results of this indicate that learners trained on nucleotide diversity perform significantly better than those trained on presence/absence encodings. This study used supervised learning to identify individuals with high accuracy and associated stable features from skin microbiomes over a period of up to almost 3 years. These selected features provide a preliminary marker panel for future development of a robust and reproducible method for skin microbiome profiling for forensic human identification.Importance A novel approach is described to attribute skin microbiomes, collected over a period of >2.5 years, to their individual hosts with a high degree of accuracy. Nucleotide diversities of stable clade-specific markers with supervised learning was used to classify skin microbiomes from a particular individual with up to 100% classification accuracy for three body sites. Attribute selection was used to identify 187 genetic markers from 12 clades which provide the greatest differentiation of individual skin microbiomes from 14 skin sites. This study performs skin microbiome profiling from a supervised learning approach and obtains high classification accuracy for samples collected from individuals over a relatively long time period for potential application to forensic human identification.}, } @article {pmid28874411, year = {2018}, author = {Méndez-García, C and Barbas, C and Ferrer, M and Rojo, D}, title = {Complementary Methodologies To Investigate Human Gut Microbiota in Host Health, Working towards Integrative Systems Biology.}, journal = {Journal of bacteriology}, volume = {200}, number = {3}, pages = {}, doi = {10.1128/JB.00376-17}, pmid = {28874411}, issn = {1098-5530}, mesh = {Animals ; Feces/microbiology ; *Gastrointestinal Microbiome ; Health ; Homeostasis ; Humans ; Systems Biology/*methods ; }, abstract = {In 1680, Antonie van Leeuwenhoek noted compositional differences in his oral and fecal microbiota, pioneering the study of the diversity of the human microbiome. From Leeuwenhoek's time to successful modern attempts at changing the gut microbial landscape to cure disease, there has been an exponential increase in the recognition of our resident microbes as part of ourselves. Thus, the human host and microbiome have evolved in parallel to configure a balanced system in which microbes survive in homeostasis with our innate and acquired immune systems, unless disease occurs. A growing number of studies have demonstrated a correlation between the presence/absence of microbial taxa and some of their functional molecules (i.e., genes, proteins, and metabolites) with health and disease states. Nevertheless, misleading experimental design on human subjects and the cost and lack of standardized animal models pose challenges to answering the question of whether changes in microbiome composition are cause or consequence of a certain biological state. In this review, we evaluate the state of the art of methodologies that enable the study of the gut microbiome, encouraging a change in broadly used analytic strategies by choosing effector molecules (proteins and metabolites) in combination with coding nucleic acids. We further explore microbial and effector microbial product imbalances that relate to disease and health.}, } @article {pmid28872698, year = {2017}, author = {Zhang, Y and Han, SW and Cox, LM and Li, H}, title = {A multivariate distance-based analytic framework for microbial interdependence association test in longitudinal study.}, journal = {Genetic epidemiology}, volume = {41}, number = {8}, pages = {769-778}, doi = {10.1002/gepi.22065}, pmid = {28872698}, issn = {1098-2272}, support = {R01 DK090989/DK/NIDDK NIH HHS/United States ; R01 DK110014/DK/NIDDK NIH HHS/United States ; U01 CA170948/CA/NCI NIH HHS/United States ; U01 CA182370/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Bacteria/drug effects/genetics/growth & development ; Bifidobacterium/drug effects/genetics/growth & development ; DNA, Bacterial/chemistry/genetics ; High-Throughput Nucleotide Sequencing ; Humans ; Internet ; Intestines/*microbiology ; Longitudinal Studies ; Mice ; *Microbiota ; *Models, Genetic ; Penicillins/pharmacology ; Sequence Analysis, DNA ; User-Computer Interface ; }, abstract = {Human microbiome is the collection of microbes living in and on the various parts of our body. The microbes living on our body in nature do not live alone. They act as integrated microbial community with massive competing and cooperating and contribute to our human health in a very important way. Most current analyses focus on examining microbial differences at a single time point, which do not adequately capture the dynamic nature of the microbiome data. With the advent of high-throughput sequencing and analytical tools, we are able to probe the interdependent relationship among microbial species through longitudinal study. Here, we propose a multivariate distance-based test to evaluate the association between key phenotypic variables and microbial interdependence utilizing the repeatedly measured microbiome data. Extensive simulations were performed to evaluate the validity and efficiency of the proposed method. We also demonstrate the utility of the proposed test using a well-designed longitudinal murine experiment and a longitudinal human study. The proposed methodology has been implemented in the freely distributed open-source R package and Python code.}, } @article {pmid28866243, year = {2018}, author = {Heeney, DD and Gareau, MG and Marco, ML}, title = {Intestinal Lactobacillus in health and disease, a driver or just along for the ride?.}, journal = {Current opinion in biotechnology}, volume = {49}, number = {}, pages = {140-147}, doi = {10.1016/j.copbio.2017.08.004}, pmid = {28866243}, issn = {1879-0429}, support = {R01 AT009365/AT/NCCIH NIH HHS/United States ; }, abstract = {Metagenomics and related methods have led to significant advances in our understanding of the human microbiome. Members of the genus Lactobacillus, although best understood for essential roles in food fermentations and applications as probiotics, have also come to the fore in a number of untargeted gut microbiome studies in humans and animals. Even though Lactobacillus is only a minor member of the human colonic microbiota, the proportions of those bacteria are frequently either positively or negatively correlated with human disease and chronic conditions. Recent findings on Lactobacillus species in human and animal microbiome research, together with the increased knowledge on probiotic and other ingested lactobacilli, have resulted in new perspectives on the importance of this genus to human health.}, } @article {pmid28856733, year = {2017}, author = {Barr, JJ}, title = {A bacteriophages journey through the human body.}, journal = {Immunological reviews}, volume = {279}, number = {1}, pages = {106-122}, doi = {10.1111/imr.12565}, pmid = {28856733}, issn = {1600-065X}, mesh = {Animals ; Bacteria/*virology ; Bacteriophages/*immunology ; Homeostasis ; Human Body ; Humans ; Immune System/microbiology/*virology ; Intestines/microbiology/*virology ; *Microbiota ; Mucous Membrane/microbiology/*virology ; }, abstract = {The human body is colonized by a diverse collective of microorganisms, including bacteria, fungi, protozoa and viruses. The smallest entity of this microbial conglomerate are the bacterial viruses. Bacteriophages, or phages for short, exert significant selective pressure on their bacterial hosts, undoubtedly influencing the human microbiome and its impact on our health and well-being. Phages colonize all niches of the body, including the skin, oral cavity, lungs, gut, and urinary tract. As such our bodies are frequently and continuously exposed to diverse collections of phages. Despite the prevalence of phages throughout our bodies, the extent of their interactions with human cells, organs, and immune system is still largely unknown. Phages physically interact with our mucosal surfaces, are capable of bypassing epithelial cell layers, disseminate throughout the body and may manipulate our immune system. Here, I establish the novel concept of an "intra-body phageome," which encompasses the collection of phages residing within the classically "sterile" regions of the body. This review will take a phage-centric view of the microbiota, human body, and immune system with the ultimate goal of inspiring a greater appreciation for both the indirect and direct interactions between bacteriophages and their mammalian hosts.}, } @article {pmid28846702, year = {2017}, author = {Abdelmaksoud, AA and Girerd, PH and Garcia, EM and Brooks, JP and Leftwich, LM and Sheth, NU and Bradley, SP and Serrano, MG and Fettweis, JM and Huang, B and Strauss, JF and Buck, GA and Jefferson, KK}, title = {Association between statin use, the vaginal microbiome, and Gardnerella vaginalis vaginolysin-mediated cytotoxicity.}, journal = {PloS one}, volume = {12}, number = {8}, pages = {e0183765}, doi = {10.1371/journal.pone.0183765}, pmid = {28846702}, issn = {1932-6203}, support = {P60 MD002256/MD/NIMHD NIH HHS/United States ; }, mesh = {Bacterial Proteins/*physiology ; Bacterial Toxins ; Cell Survival/*physiology ; Colony Count, Microbial ; Epithelial Cells/metabolism ; Female ; Gardnerella vaginalis/isolation & purification/*metabolism ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/*pharmacology ; Microbiota/*drug effects/genetics ; Middle Aged ; RNA, Ribosomal, 16S/genetics ; Simvastatin/*pharmacology ; Vagina/*microbiology ; }, abstract = {BACKGROUND: Bacterial vaginosis (BV) is the leading dysbiosis of the vaginal microbiome. The pathways leading towards the development of BV are not well understood. Gardnerella vaginalis is frequently associated with BV. G. vaginalis produces the cholesterol-dependent cytolysin (CDC), vaginolysin, which can lyse a variety of human cells and is thought to play a role in pathogenesis. Because membrane cholesterol is required for vaginolysin to function, and because HMG-CoA reductase inhibitors (statins) affect not only serum levels of cholesterol but membrane levels as well, we hypothesized that statins might affect the vaginal microbiome.

METHODS: To investigate the relationship between use of the statins and the vaginal microbiome, we analyzed 16S rRNA gene taxonomic surveys performed on vaginal samples from 133 women who participated in the Vaginal Human Microbiome Project and who were taking statins at the time of sampling, 152 women who reported high cholesterol levels but were not taking statins, and 316 women who did not report high cholesterol. To examine the effect of statins on the cytolytic effect of vaginolysin, the cholesterol-dependent cytolysin (CDC) produced by Gardnerella vaginalis, we assessed the effect of simvastatin pretreatment of VK2E6/E7 vaginal epithelial cells on vaginolysin-mediated cytotoxicity.

RESULTS: The mean proportion of G. vaginalis among women taking statins was significantly lower relative to women not using statins. Women using statins had higher mean proportions of Lactobacillus crispatus relative to women with normal cholesterol levels, and higher levels of Lactobacillus jensenii relative to women with high cholesterol but not taking statins. In vitro, vaginal epithelial cells pretreated with simvastatin were relatively resistant to vaginolysin and this effect was inhibited by cholesterol.

CONCLUSIONS: In this cross-sectional study, statin use was associated with reduced proportions of G. vaginalis and greater proportions of beneficial lactobacilli within the vaginal microbiome. The negative association between statin use and G. vaginalis may be related to inhibition of vaginolysin function.}, } @article {pmid28845973, year = {2018}, author = {Chu, J and Vila-Farres, X and Inoyama, D and Gallardo-Macias, R and Jaskowski, M and Satish, S and Freundlich, JS and Brady, SF}, title = {Human Microbiome Inspired Antibiotics with Improved β-Lactam Synergy against MDR Staphylococcus aureus.}, journal = {ACS infectious diseases}, volume = {4}, number = {1}, pages = {33-38}, doi = {10.1021/acsinfecdis.7b00056}, pmid = {28845973}, issn = {2373-8227}, abstract = {The flippase MurJ is responsible for transporting the cell wall intermediate lipid II from the cytoplasm to the outside of the cell. While essential for the survival of bacteria, it remains an underexploited target for antibacterial therapy. The humimycin antibiotics are lipid II flippase (MurJ) inhibitors that were synthesized on the basis of bioinformatic predictions derived from secondary metabolite gene clusters found in the human microbiome. Here, we describe an SAR campaign around humimycin A that produced humimycin 17S. Compared to humimycin A, 17S is a more potent β-lactam potentiator, has a broader spectrum of activity, which now includes both methicillin resistant Staphylococcus aureus (MRSA) and vancomycin resistant Enterococcus faecalis (VRE), and did not lead to any detectable resistance when used in combination with a β-lactam. Combinations of β-lactam and humimycin 17S provide a potentially useful long-term MRSA regimen.}, } @article {pmid28842845, year = {2017}, author = {Li, DY and Tang, WHW}, title = {Gut Microbiota and Atherosclerosis.}, journal = {Current atherosclerosis reports}, volume = {19}, number = {10}, pages = {39}, doi = {10.1007/s11883-017-0675-9}, pmid = {28842845}, issn = {1534-6242}, mesh = {Animals ; *Atherosclerosis/drug therapy/metabolism/microbiology ; Bile Acids and Salts/metabolism ; Carnitine/metabolism ; Diet ; Disease Models, Animal ; *Gastrointestinal Microbiome/immunology ; Humans ; Methylamines/*metabolism ; }, abstract = {PURPOSE OF REVIEW: Studies in microbiota-mediated health risks have gained traction in recent years since the compilation of the Human Microbiome Project. No longer do we believe that our gut microbiota is an inert set of microorganisms that reside in the body without consequence. In this review, we discuss the recent findings which further our understanding of the connection between the gut microbiota and the atherosclerosis.

RECENT FINDINGS: We evaluate studies which illustrate the current understanding of the relationship between infection, immunity, altered metabolism, and bacterial products such as immune activators or dietary metabolites and their contributions to the development of atherosclerosis. In particular, we critically examine rec ent clinical and mechanistic findings for the novel microbiota-dependent dietary metabolite, trimethylamine N-oxide (TMAO), which has been implicated in atherosclerosis. These discoveries are now becoming integrated with advances in microbiota profiling which enhance our ability to interrogate the functional role of the gut microbiome and develop strategies for targeted therapeutics. The gut microbiota is a multi-faceted system that is unraveling novel contributors to the development and progression of atherosclerosis. In this review, we discuss historic and novel contributors while highlighting the TMAO story mainly as an example of the various paths taken beyond deciphering microbial composition to elucidate downstream mechanisms that promote (or protect from) atherogenesis in the hopes of translating these findings from bench to bedside.}, } @article {pmid28841398, year = {2018}, author = {Chanyi, RM}, title = {The complete microbiologist, Dr. Terry Beveridge.}, journal = {Canadian journal of microbiology}, volume = {64}, number = {9}, pages = {643}, doi = {10.1139/cjm-2017-0465}, pmid = {28841398}, issn = {1480-3275}, } @article {pmid28837464, year = {2017}, author = {Clark, AP}, title = {The Human Microbiome.}, journal = {The American journal of nursing}, volume = {117}, number = {9}, pages = {13}, doi = {10.1097/01.NAJ.0000524523.42427.40}, pmid = {28837464}, issn = {1538-7488}, mesh = {Humans ; *Microbiota ; }, } @article {pmid28837129, year = {2017}, author = {Beghini, F and Pasolli, E and Truong, TD and Putignani, L and Cacciò, SM and Segata, N}, title = {Large-scale comparative metagenomics of Blastocystis, a common member of the human gut microbiome.}, journal = {The ISME journal}, volume = {11}, number = {12}, pages = {2848-2863}, doi = {10.1038/ismej.2017.139}, pmid = {28837129}, issn = {1751-7370}, mesh = {Adolescent ; Adult ; Aged ; Blastocystis/classification/genetics/*isolation & purification ; Crohn Disease/parasitology ; Dysbiosis/parasitology ; Feces/parasitology ; Female ; Gastrointestinal Tract/*parasitology ; Humans ; Male ; Metagenomics ; Middle Aged ; Prevalence ; Young Adult ; }, abstract = {The influence of unicellular eukaryotic microorganisms on human gut health and disease is still largely unexplored. Blastocystis spp. commonly colonize the gut, but its clinical significance and ecological role are currently unsettled. We have developed a high-sensitivity bioinformatic pipeline to detect Blastocystis subtypes (STs) from shotgun metagenomics, and applied it to 12 large data sets, comprising 1689 subjects of different geographic origin, disease status and lifestyle. We confirmed and extended previous observations on the high prevalence the microrganism in the population (14.9%), its non-random and ST-specific distribution, and its ability to cause persistent (asymptomatic) colonization. These findings, along with the higher prevalence observed in non-westernized individuals, the lack of positive association with any of the disease considered, and decreased presence in individuals with dysbiosis associated with colorectal cancer and Crohn's disease, strongly suggest that Blastocystis is a component of the healthy gut microbiome. Further, we found an inverse association between body mass index and Blastocystis, and strong co-occurrence with archaeal organisms (Methanobrevibacter smithii) and several bacterial species. The association of specific microbial community structures with Blastocystis was confirmed by the high predictability (up to 0.91 area under the curve) of the microorganism colonization based on the species-level composition of the microbiome. Finally, we reconstructed and functionally profiled 43 new draft Blastocystis genomes and discovered a higher intra subtype variability of ST1 and ST2 compared with ST3 and ST4. Altogether, we provide an in-depth epidemiologic, ecological, and genomic analysis of Blastocystis, and show how metagenomics can be crucial to advance population genomics of human parasites.}, } @article {pmid28830999, year = {2017}, author = {Kowarsky, M and Camunas-Soler, J and Kertesz, M and De Vlaminck, I and Koh, W and Pan, W and Martin, L and Neff, NF and Okamoto, J and Wong, RJ and Kharbanda, S and El-Sayed, Y and Blumenfeld, Y and Stevenson, DK and Shaw, GM and Wolfe, ND and Quake, SR}, title = {Numerous uncharacterized and highly divergent microbes which colonize humans are revealed by circulating cell-free DNA.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {114}, number = {36}, pages = {9623-9628}, doi = {10.1073/pnas.1707009114}, pmid = {28830999}, issn = {1091-6490}, mesh = {Cell-Free Nucleic Acids/*blood/*genetics ; DNA, Bacterial/*blood/*genetics ; DNA, Viral/*blood/*genetics ; Genetic Variation ; High-Throughput Nucleotide Sequencing/methods ; Humans ; Metagenomics/methods ; Microbiota/*genetics ; Phylogeny ; }, abstract = {Blood circulates throughout the human body and contains molecules drawn from virtually every tissue, including the microbes and viruses which colonize the body. Through massive shotgun sequencing of circulating cell-free DNA from the blood, we identified hundreds of new bacteria and viruses which represent previously unidentified members of the human microbiome. Analyzing cumulative sequence data from 1,351 blood samples collected from 188 patients enabled us to assemble 7,190 contiguous regions (contigs) larger than 1 kbp, of which 3,761 are novel with little or no sequence homology in any existing databases. The vast majority of these novel contigs possess coding sequences, and we have validated their existence both by finding their presence in independent experiments and by performing direct PCR amplification. When their nearest neighbors are located in the tree of life, many of the organisms represent entirely novel taxa, showing that microbial diversity within the human body is substantially broader than previously appreciated.}, } @article {pmid28825919, year = {2017}, author = {Dunn, AB and Jordan, S and Baker, BJ and Carlson, NS}, title = {The Maternal Infant Microbiome: Considerations for Labor and Birth.}, journal = {MCN. The American journal of maternal child nursing}, volume = {42}, number = {6}, pages = {318-325}, doi = {10.1097/NMC.0000000000000373}, pmid = {28825919}, issn = {1539-0683}, support = {F31 NR015400/NR/NINR NIH HHS/United States ; R01 NR014800/NR/NINR NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Anti-Bacterial Agents/adverse effects/therapeutic use ; Cesarean Section/adverse effects ; Female ; Gastrointestinal Microbiome/*physiology ; Humans ; Infant, Newborn ; Maternal-Fetal Exchange/*physiology ; Mothers/statistics & numerical data ; Parturition/physiology ; Pregnancy ; }, abstract = {The human microbiome plays a role in maintaining health, but is also thought to attenuate and exacerbate risk factors for adverse maternal-child health outcomes. The development of the microbiome begins in utero; however, factors related to the labor and birth environment have been shown to influence the initial colonization process of the newborn microbiome. This "seeding" or transfer of microbes from the mother to newborn may serve as an early inoculation process with implications for the long-term health outcomes of newborns. Studies have shown that there are distinct differences in the microbiome profiles of newborns born vaginally compared with those born by cesarean. Antibiotic exposure has been shown to alter the microbial profiles of women and may influence the gut microbial profiles of their newborns. Considering that the first major microbial colonization occurs at birth, it is essential that labor and birth nurses be aware of factors that may alter the composition of the microbiome during the labor and birth process. The implications of various activities and factors unique to the labor and birth environment that may influence the microbiome of women and newborns during the labor and birth process (e.g., route of birth, antibiotic use, nursing procedures) are presented with a focus on the role of labor nurses and the potential influence of nursing activities on this process.}, } @article {pmid28824902, year = {2017}, author = {Agarwal, D and Dhotre, D and Patil, R and Shouche, Y and Juvekar, S and Salvi, S}, title = {Potential of Health and Demographic Surveillance System in Asthma and Chronic Obstructive Pulmonary Disease Microbiome Research.}, journal = {Frontiers in public health}, volume = {5}, number = {}, pages = {196}, doi = {10.3389/fpubh.2017.00196}, pmid = {28824902}, issn = {2296-2565}, abstract = {Health and demographic surveillance system (HDSS) is a population-based health and vital event registration system that monitors demographic and health events in a geographically defined population at regular intervals. Human microbiome research in the past decade has been the field of increasingly intense research much due to its demonstrated impact upon various health conditions including human chronic airway diseases such as asthma and chronic obstructive pulmonary disease (COPD). Many confounding factors have been revealed to play a role in shaping the microbiome in chronic airway diseases. Asthma and COPD follows a typical pattern of disease progression, which includes stable and exacerbation state in which the microbiota is known to vary. However, many such studies lack extensive and longitudinal sampling with inadequate metadata, which has resulted in the inconsistencies in the observations. HDSS provides such a platform, which can offer a deeper understanding of the role of the microbiome in human health. In this review, we highlight opportunities and limitations in microbiome research with the help of studies conducted on chronic airway diseases like asthma and COPD. In addition, we also emphasize on the benefits of HDSS and future directions in lung microbiome research.}, } @article {pmid28821012, year = {2017}, author = {Fukuyama, J and Rumker, L and Sankaran, K and Jeganathan, P and Dethlefsen, L and Relman, DA and Holmes, SP}, title = {Multidomain analyses of a longitudinal human microbiome intestinal cleanout perturbation experiment.}, journal = {PLoS computational biology}, volume = {13}, number = {8}, pages = {e1005706}, doi = {10.1371/journal.pcbi.1005706}, pmid = {28821012}, issn = {1553-7358}, mesh = {Adult ; DNA, Bacterial/analysis/genetics ; Diarrhea ; Female ; Gastrointestinal Microbiome/*genetics ; Humans ; Longitudinal Studies ; Male ; Metagenome/*genetics ; Metagenomics/*methods ; Middle Aged ; *Models, Biological ; Principal Component Analysis ; RNA, Ribosomal, 16S/genetics ; Young Adult ; }, abstract = {Our work focuses on the stability, resilience, and response to perturbation of the bacterial communities in the human gut. Informative flash flood-like disturbances that eliminate most gastrointestinal biomass can be induced using a clinically-relevant iso-osmotic agent. We designed and executed such a disturbance in human volunteers using a dense longitudinal sampling scheme extending before and after induced diarrhea. This experiment has enabled a careful multidomain analysis of a controlled perturbation of the human gut microbiota with a new level of resolution. These new longitudinal multidomain data were analyzed using recently developed statistical methods that demonstrate improvements over current practices. By imposing sparsity constraints we have enhanced the interpretability of the analyses and by employing a new adaptive generalized principal components analysis, incorporated modulated phylogenetic information and enhanced interpretation through scoring of the portions of the tree most influenced by the perturbation. Our analyses leverage the taxa-sample duality in the data to show how the gut microbiota recovers following this perturbation. Through a holistic approach that integrates phylogenetic, metagenomic and abundance information, we elucidate patterns of taxonomic and functional change that characterize the community recovery process across individuals. We provide complete code and illustrations of new sparse statistical methods for high-dimensional, longitudinal multidomain data that provide greater interpretability than existing methods.}, } @article {pmid28819919, year = {2017}, author = {Houf, JR}, title = {The Microbial Mother Meets the Independent Organ: Cultural Discourses of Reproductive Microbiomes.}, journal = {The Journal of medical humanities}, volume = {}, number = {}, pages = {}, doi = {10.1007/s10912-017-9468-y}, pmid = {28819919}, issn = {1573-3645}, abstract = {The human microbiome is changing the way experts and non-experts think about germs and microorganisms. This essay is a gender analysis of contemporary discourses surrounding the human reproductive microbiome, specifically the vaginal microbiota and the penile microbiota. I first historically situate the human reproductive microbiome within the germ theory of disease. Then, I draw on Heather Paxson's Foucauldian and Latourian concept of microbiopolitics to argue that microbiopolitics is not only about how humans should live with microorganisms; but it also impacts how humans and microbes live together as gendered beings. I illustrate this gendering through two figures: the microbial mother and the independent organ.}, } @article {pmid28813450, year = {2017}, author = {Chen, H and Peng, S and Dai, L and Zou, Q and Yi, B and Yang, X and Ma, ZS}, title = {Oral microbial community assembly under the influence of periodontitis.}, journal = {PloS one}, volume = {12}, number = {8}, pages = {e0182259}, doi = {10.1371/journal.pone.0182259}, pmid = {28813450}, issn = {1932-6203}, mesh = {Algorithms ; *Biodiversity ; Case-Control Studies ; Datasets as Topic ; Humans ; Metagenome ; Metagenomics/methods ; *Microbiota ; Models, Theoretical ; Mouth Mucosa/*microbiology ; Periodontitis/*microbiology ; }, abstract = {Several ecological hypotheses (e.g., specific plaque, non-specific plaque and keystone pathogen) regarding the etiology of periodontitis have been proposed since the 1990s, most of which have been centered on the concept of dysbiosis associated with periodontitis. Nevertheless, none of the existing hypotheses have presented mechanistic interpretations on how and why dysbiosis actually occurs. Hubbell's neutral theory of biodiversity offers a powerful null model to test hypothesis regarding the mechanism of community assembly and diversity maintenance from the metagenomic sequencing data, which can help to understand the forces that shape the community dynamics such as dysbiosis. Here we reanalyze the dataset from Abusleme et al.'s comparative study of the oral microbial communities from periodontitis patients and healthy individuals. Our study demonstrates that 14 out of 61 communities (23%) passed the neutrality test, a percentage significantly higher than the previous reported neutrality rate of 1% in human microbiome (Li & Ma 2016, Scientific Reports). This suggests that, while the niche selection may play a predominant role in the assembly and diversity maintenance in oral microbiome, the effect of neutral dynamics may not be ignored. However, no statistically significant differences in the neutrality passing rates were detected between the periodontitis and healthy treatments with Fisher's exact probability test and multiple testing corrections, suggesting that the mechanism of community assembly is robust against disturbances such as periodontitis. In addition, our study confirmed previous finding that periodontitis patients exhibited higher biodiversity. These findings suggest that while periodontitis may significantly change the community composition measured by diversity (i.e., the exhibition or 'phenotype' of community assembly), it does not seem to cause the 'mutation' of the 'genotype" (mechanism) of community assembly. We argue that the 'phenotypic' changes explain the observed link (not necessarily causal) between periodontitis and community dysbiosis, which is certainly worthy of further investigation.}, } @article {pmid28810737, year = {2018}, author = {Cohen, LJ and Han, S and Huang, YH and Brady, SF}, title = {Identification of the Colicin V Bacteriocin Gene Cluster by Functional Screening of a Human Microbiome Metagenomic Library.}, journal = {ACS infectious diseases}, volume = {4}, number = {1}, pages = {27-32}, doi = {10.1021/acsinfecdis.7b00081}, pmid = {28810737}, issn = {2373-8227}, abstract = {The forces that shape human microbial ecology are complex. It is likely that human microbiota, similarly to other microbiomes, use antibiotics as one way to establish an ecological niche. In this study, we use functional metagenomics to identify human microbial gene clusters that encode for antibiotic functions. Screening of a metagenomic library prepared from a healthy patient stool sample led to the identification of a family of clones with inserts that are 99% identical to a region of a virulence plasmid found in avian pathogenic Escherichia coli. Characterization of the metagenomic DNA sequence identified a colicin V biosynthetic cluster as being responsible for the observed antibiotic effect of the metagenomic clone against E. coli. This study presents a scalable method to recover antibiotic gene clusters from humans using functional metagenomics and highlights a strategy to study bacteriocins in the human microbiome which can provide a resource for therapeutic discovery.}, } @article {pmid28808691, year = {2017}, author = {Yasuda, K and Hsu, T and Gallini, CA and Mclver, LJ and Schwager, E and Shi, A and DuLong, CR and Schwager, RN and Abu-Ali, GS and Franzosa, EA and Garrett, WS and Huttenhower, C and Morgan, XC}, title = {Fluoride Depletes Acidogenic Taxa in Oral but Not Gut Microbial Communities in Mice.}, journal = {mSystems}, volume = {2}, number = {4}, pages = {}, doi = {10.1128/mSystems.00047-17}, pmid = {28808691}, issn = {2379-5077}, support = {R01 CA154426/CA/NCI NIH HHS/United States ; }, abstract = {Fluoridation of drinking water and dental products prevents dental caries primarily by inhibiting energy harvest in oral cariogenic bacteria (such as Streptococcus mutans and Streptococcus sanguinis), thus leading to their depletion. However, the extent to which oral and gut microbial communities are affected by host fluoride exposure has been underexplored. In this study, we modeled human fluoride exposures to municipal water and dental products by treating mice with low or high levels of fluoride over a 12-week period. We then used 16S rRNA gene amplicon and shotgun metagenomic sequencing to assess fluoride's effects on oral and gut microbiome composition and function. In both the low- and high-fluoride groups, several operational taxonomic units (OTUs) belonging to acidogenic bacterial genera (such as Parabacteroides, Bacteroides, and Bilophila) were depleted in the oral community. In addition, fluoride-associated changes in oral community composition resulted in depletion of gene families involved in central carbon metabolism and energy harvest (2-oxoglutarate ferredoxin oxidoreductase, succinate dehydrogenase, and the glyoxylate cycle). In contrast, fluoride treatment did not induce a significant shift in gut microbial community composition or function in our mouse model, possibly due to absorption in the upper gastrointestinal tract. Fluoride-associated perturbations thus appeared to have a selective effect on the composition of the oral but not gut microbial community in mice. Future studies will be necessary to understand possible implications of fluoride exposure for the human microbiome. IMPORTANCE Fluoride has been added to drinking water and dental products since the 1950s. The beneficial effects of fluoride on oral health are due to its ability to inhibit the growth of bacteria that cause dental caries. Despite widespread human consumption of fluoride, there have been only two studies of humans that considered the effect of fluoride on human-associated microbial communities, which are increasingly understood to play important roles in health and disease. Notably, neither of these studies included a true cross-sectional control lacking fluoride exposure, as study subjects continued baseline fluoride treatment in their daily dental hygiene routines. To our knowledge, this work (in mice) is the first controlled study to assess the independent effects of fluoride exposure on the oral and gut microbial communities. Investigating how fluoride interacts with host-associated microbial communities in this controlled setting represents an effort toward understanding how common environmental exposures may potentially influence health.}, } @article {pmid28800826, year = {2017}, author = {Siroli, L and Patrignani, F and Serrazanetti, DI and Vernocchi, P and Del Chierico, F and Russo, A and Torriani, S and Putignani, L and Gardini, F and Lanciotti, R}, title = {Effect of thyme essential oil and Lactococcus lactis CBM21 on the microbiota composition and quality of minimally processed lamb's lettuce.}, journal = {Food microbiology}, volume = {68}, number = {}, pages = {61-70}, doi = {10.1016/j.fm.2017.06.017}, pmid = {28800826}, issn = {1095-9998}, mesh = {Bacteria/classification/*drug effects/growth & development/isolation & purification ; Biodiversity ; Food Contamination/prevention & control ; Lactococcus lactis/*physiology ; Lettuce/*microbiology ; Oils, Volatile/isolation & purification/*pharmacology ; Plant Extracts/isolation & purification/*pharmacology ; Thymus Plant/*chemistry ; Vegetables/*microbiology ; }, abstract = {The main aim of this work was to evaluate, at pilot scale in an industrial environment, the effects of the biocontrol agent Lactococcus lactis CBM21 and thyme essential oil compared to chlorine, used in the washing step of fresh-cut lamb's lettuce, on the microbiota and its changes in relation to the time of storage. The modification of the microbial population was studied through pyrosequencing in addition to the traditional plate counts. In addition, the volatile molecule and sensory profiles were evaluated during the storage. The results showed no significant differences in terms of total aerobic mesophilic cell loads in relation to the washing solution adopted. However, the pyrosequencing data permitted to identify the genera and species able to dominate the spoilage associations over storage in relation to the treatment applied. Also, the analyses of the volatile molecule profiles of the samples during storage allowed the identification of specific molecules as markers of the spoilage for each different treatment. The sensory analyses after 3 and 5 days of storage showed the preference of the panelists for samples washed with the combination thyme EO and the biocontrol agent. These samples were preferred for attributes such as flavor, acceptability and overall quality. These results highlighted the effect of the innovative washing solutions on the quality of lettuce through the shift of microbiota towards genera and species with lower potential in decreasing the sensory properties of the product.}, } @article {pmid28793934, year = {2017}, author = {Caparrós-Martín, JA and Lareu, RR and Ramsay, JP and Peplies, J and Reen, FJ and Headlam, HA and Ward, NC and Croft, KD and Newsholme, P and Hughes, JD and O'Gara, F}, title = {Statin therapy causes gut dysbiosis in mice through a PXR-dependent mechanism.}, journal = {Microbiome}, volume = {5}, number = {1}, pages = {95}, doi = {10.1186/s40168-017-0312-4}, pmid = {28793934}, issn = {2049-2618}, mesh = {Animals ; Bile Acids and Salts/analysis ; Blood Glucose/analysis ; Butyrates/analysis ; Diabetes Mellitus, Type 2/etiology ; Dysbiosis/*etiology/physiopathology ; Gastrointestinal Microbiome/*drug effects ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/*adverse effects/therapeutic use ; Intestines/*drug effects/microbiology/physiopathology ; Lipid Metabolism/genetics ; Male ; Mice ; Mice, Knockout ; Receptors, Steroid/*genetics ; Weight Gain/drug effects ; }, abstract = {BACKGROUND: Statins are a class of therapeutics used to regulate serum cholesterol and reduce the risk of heart disease. Although statins are highly effective in removing cholesterol from the blood, their consumption has been linked to potential adverse effects in some individuals. The most common events associated with statin intolerance are myopathy and increased risk of developing type 2 diabetes mellitus. However, the pathological mechanism through which statins cause these adverse effects is not well understood.

RESULTS: Using a murine model, we describe for the first time profound changes in the microbial composition of the gut following statin treatment. This remodelling affected the diversity and metabolic profile of the gut microbiota and was associated with reduced production of butyrate. Statins altered both the size and composition of the bile acid pool in the intestine, tentatively explaining the observed gut dysbiosis. As also observed in patients, statin-treated mice trended towards increased fasting blood glucose levels and weight gain compared to controls. Statin treatment affected the hepatic expression of genes involved in lipid and glucose metabolism. Using gene knockout mice, we demonstrated that the observed effects were mediated through pregnane X receptor (PXR).

CONCLUSION: This study demonstrates that statin therapy drives a profound remodelling of the gut microbiota, hepatic gene deregulation and metabolic alterations in mice through a PXR-dependent mechanism. Since the demonstrated importance of the intestinal microbial community in host health, this work provides new perspectives to help prevent the statin-associated unintended metabolic effects.}, } @article {pmid28785422, year = {2017}, author = {Gundogdu, A and Nalbantoglu, U}, title = {Human genome-microbiome interaction: metagenomics frontiers for the aetiopathology of autoimmune diseases.}, journal = {Microbial genomics}, volume = {3}, number = {4}, pages = {e000112}, doi = {10.1099/mgen.0.000112}, pmid = {28785422}, issn = {2057-5858}, abstract = {A short while ago, the human genome and microbiome were analysed simultaneously for the first time as a multi-omic approach. The analyses of heterogeneous population cohorts showed that microbiome components were associated with human genome variations. In-depth analysis of these results reveals that the majority of those relationships are between immune pathways and autoimmune disease-associated microbiome components. Thus, it can be hypothesized that autoimmunity may be associated with homeostatic disequilibrium of the human-microbiome interactome. Further analysis of human genome-human microbiome relationships in disease contexts with tailored systems biology approaches may yield insights into disease pathogenesis and prognosis.}, } @article {pmid28777382, year = {2017}, author = {Adam, PS and Borrel, G and Brochier-Armanet, C and Gribaldo, S}, title = {The growing tree of Archaea: new perspectives on their diversity, evolution and ecology.}, journal = {The ISME journal}, volume = {11}, number = {11}, pages = {2407-2425}, doi = {10.1038/ismej.2017.122}, pmid = {28777382}, issn = {1751-7370}, mesh = {Archaea/*classification/genetics/*isolation & purification ; *Biodiversity ; Ecology ; Genome, Archaeal ; Phylogeny ; }, abstract = {The Archaea occupy a key position in the Tree of Life, and are a major fraction of microbial diversity. Abundant in soils, ocean sediments and the water column, they have crucial roles in processes mediating global carbon and nutrient fluxes. Moreover, they represent an important component of the human microbiome, where their role in health and disease is still unclear. The development of culture-independent sequencing techniques has provided unprecedented access to genomic data from a large number of so far inaccessible archaeal lineages. This is revolutionizing our view of the diversity and metabolic potential of the Archaea in a wide variety of environments, an important step toward understanding their ecological role. The archaeal tree is being rapidly filled up with new branches constituting phyla, classes and orders, generating novel challenges for high-rank systematics, and providing key information for dissecting the origin of this domain, the evolutionary trajectories that have shaped its current diversity, and its relationships with Bacteria and Eukarya. The present picture is that of a huge diversity of the Archaea, which we are only starting to explore.}, } @article {pmid28771951, year = {2017}, author = {Wong, WF and Santiago, M}, title = {Microbial approaches for targeting antibiotic-resistant bacteria.}, journal = {Microbial biotechnology}, volume = {10}, number = {5}, pages = {1047-1053}, doi = {10.1111/1751-7915.12783}, pmid = {28771951}, issn = {1751-7915}, mesh = {Animals ; Anti-Bacterial Agents/*pharmacology ; Bacteria/*drug effects/genetics/metabolism ; Bacterial Infections/*microbiology/therapy ; *Drug Resistance, Bacterial ; Humans ; Microbiota ; }, abstract = {Antibiotic resistant bacterial infections are a global public health challenge that has been increasing in severity and scope for the last few decades. Without creative solutions to this problem, treatment of injuries and infections will become progressively more challenging. A better understanding of the human microbiome has led to a new appreciation for the role commensal microbes play in protecting us from pathogens, especially in the gut. Antibiotics lead to disruption of the gut microbial ecosystem, enabling colonization by antibiotic resistant bacterial pathogens. Many different lines of research have identified specific bacterial taxa and mechanisms that play a role in colonization resistance, and these lines of research may one day lead to microbial therapeutics targeting antibiotic resistant bacteria. Here, we discuss a few of these strategies and the challenges they will need to overcome in order to become an effective therapeutic.}, } @article {pmid28771841, year = {2017}, author = {Boost, M and Cho, P and Wang, Z}, title = {Disturbing the balance: effect of contact lens use on the ocular proteome and microbiome.}, journal = {Clinical & experimental optometry}, volume = {100}, number = {5}, pages = {459-472}, doi = {10.1111/cxo.12582}, pmid = {28771841}, issn = {1444-0938}, mesh = {Contact Lenses/*utilization ; Cornea/*metabolism ; Humans ; Microbiota/*physiology ; Proteome/*metabolism ; Proteostasis/*physiology ; Refractive Errors/therapy ; Tears/*metabolism ; Vision Disorders/therapy ; }, abstract = {Contact lens wear is a popular, convenient and effective method for vision correction. In recent years, contact lens practice has expanded to include new paradigms, including orthokeratology; however, their use is not entirely without risk, as the incidence of infection has consistently been reported to be higher in contact lens wearers. The explanations for this increased susceptibility have largely focused on physical damage, especially to the cornea, due to a combination of hypoxia, mechanical trauma, deposits and solution cytotoxicity, as well as poor compliance with care routines leading to introduction of pathogens into the ocular environment. However, in recent years, with the increasing availability and reduced cost of molecular techniques, the ocular environment has received greater attention with in-depth studies of proteins and other components. Numerous proteins were found to be present in the tears and their functions and interactions indicate that the tears are far more complex than formerly presumed. In addition, the concept of a sterile or limited microbial population on the ocular surface has been challenged by analysis of the microbiome. Ocular microbiome was not considered as one of the key sites for the Human Microbiome Project, as it was thought to be limited compared to other body sites. This was proven to be fallacious, as a wide variety of micro-organisms were identified in the analyses of human tears. Thus, the ocular environment is now recognised to be more complicated and interference with this ecological balance may lead to adverse effects. The use of contact lenses clearly changes the situation at the ocular surface, which may result in consequences which disturb the balance in the healthy eye.}, } @article {pmid28769875, year = {2017}, author = {Vecchio-Pagan, B and Bewick, S and Mainali, K and Karig, DK and Fagan, WF}, title = {A Stoichioproteomic Analysis of Samples from the Human Microbiome Project.}, journal = {Frontiers in microbiology}, volume = {8}, number = {}, pages = {1119}, doi = {10.3389/fmicb.2017.01119}, pmid = {28769875}, issn = {1664-302X}, abstract = {Ecological stoichiometry (ES) uses organism-specific elemental content to explain differences in species life histories, species interactions, community organization, environmental constraints and even ecosystem function. Although ES has been successfully applied to a range of different organisms, most emphasis on microbial ecological stoichiometry focuses on lake, ocean, and soil communities. With the recent advances in human microbiome research, however, large amounts of data are being generated that describe differences in community composition across body sites and individuals. We suggest that ES may provide a framework for beginning to understand the structure, organization, and function of human microbial communities, including why certain organisms exist at certain locations, and how they interact with both the other microbes in their environment and their human host. As a first step, we undertake a stoichioproteomic analysis of microbial communities from different body sites. Specifically, we compare and contrast the elemental composition of microbial protein samples using annotated sequencing data from 690 gut, vaginal, oral, nares, and skin samples currently available through the Human Microbiome Project. Our results suggest significant differences in both the median and variance of the carbon, oxygen, nitrogen, and sulfur contents of microbial protein samples from different locations. For example, whereas proteins from vaginal sites are high in carbon, proteins from skin and nasal sites are high in nitrogen and oxygen. Meanwhile, proteins from stool (the gut) are particularly high in sulfur content. We interpret these differences in terms of the local environments at different human body sites, including atmospheric exposure and food intake rates.}, } @article {pmid28767318, year = {2018}, author = {Malan-Muller, S and Valles-Colomer, M and Raes, J and Lowry, CA and Seedat, S and Hemmings, SMJ}, title = {The Gut Microbiome and Mental Health: Implications for Anxiety- and Trauma-Related Disorders.}, journal = {Omics : a journal of integrative biology}, volume = {22}, number = {2}, pages = {90-107}, doi = {10.1089/omi.2017.0077}, pmid = {28767318}, issn = {1557-8100}, abstract = {Biological psychiatry research has long focused on the brain in elucidating the neurobiological mechanisms of anxiety- and trauma-related disorders. This review challenges this assumption and suggests that the gut microbiome and its interactome also deserve attention to understand brain disorders and develop innovative treatments and diagnostics in the 21st century. The recent, in-depth characterization of the human microbiome spurred a paradigm shift in human health and disease. Animal models strongly suggest a role for the gut microbiome in anxiety- and trauma-related disorders. The microbiota-gut-brain (MGB) axis sits at the epicenter of this new approach to mental health. The microbiome plays an important role in the programming of the hypothalamic-pituitary-adrenal (HPA) axis early in life, and stress reactivity over the life span. In this review, we highlight emerging findings of microbiome research in psychiatric disorders, focusing on anxiety- and trauma-related disorders specifically, and discuss the gut microbiome as a potential therapeutic target. 16S rRNA sequencing has enabled researchers to investigate and compare microbial composition between individuals. The functional microbiome can be studied using methods involving metagenomics, metatranscriptomics, metaproteomics, and metabolomics, as discussed in the present review. Other factors that shape the gut microbiome should be considered to obtain a holistic view of the factors at play in the complex interactome linked to the MGB. In all, we underscore the importance of microbiome science, and gut microbiota in particular, as emerging critical players in mental illness and maintenance of mental health. This new frontier of biological psychiatry and postgenomic medicine should be embraced by the mental health community as it plays an ever-increasing transformative role in integrative and holistic health research in the next decade.}, } @article {pmid28766918, year = {2018}, author = {Sherwani, MA and Tufail, S and Muzaffar, AF and Yusuf, N}, title = {The skin microbiome and immune system: Potential target for chemoprevention?.}, journal = {Photodermatology, photoimmunology & photomedicine}, volume = {34}, number = {1}, pages = {25-34}, doi = {10.1111/phpp.12334}, pmid = {28766918}, issn = {1600-0781}, mesh = {Animals ; Gastrointestinal Microbiome ; Humans ; *Microbiota/radiation effects ; Prebiotics ; Probiotics/pharmacology ; Skin/*immunology/*microbiology ; Skin Neoplasms/immunology/*microbiology/*prevention & control ; Ultraviolet Rays ; Virus Diseases/complications ; Vitamin D/analogs & derivatives/metabolism ; }, abstract = {There has been increasing interest in understanding the role of the human microbiome in skin diseases. Microbiome studies are being utilized in skin cancer research in numerous ways. Commensal bacteria are being studied as a potential tool to judge the biggest environmental risk of skin cancer, ultraviolet (UV) radiation. Owing to the recognized link of skin microbes in the process of inflammation, there have been theories linking commensal bacteria to skin cancer. Viral metagenomics has also provided insight into virus linked forms of skin cancers. Speculations can be drawn for skin microbiome that in a manner similar to gut microbiome, they can be involved in chemoprevention of skin cancer. Nonetheless, there are definitely huge gaps in our knowledge of the relationship of microbiome and skin cancers, especially in relation to chemoprevention. The utilization of microbiome in skin cancer research seems to be a promising field and may help yield novel skin cancer prevention and treatment options. This review focuses on recent utilization of the microbiome in skin cancer research, and it explores the potential of utilizing the microbiome in prevention, earlier diagnosis, and treatment of skin cancers.}, } @article {pmid28761935, year = {2017}, author = {Ross, AA and Doxey, AC and Neufeld, JD}, title = {The Skin Microbiome of Cohabiting Couples.}, journal = {mSystems}, volume = {2}, number = {4}, pages = {}, doi = {10.1128/mSystems.00043-17}, pmid = {28761935}, issn = {2379-5077}, abstract = {Distinct microbial communities inhabit individuals as part of the human skin microbiome and are continually shed to the surrounding environment. Microbial communities from 17 skin sites of 10 sexually active cohabiting couples (20 individuals) were sampled to test whether cohabitation impacts an individual's skin microbiome, leading to shared skin microbiota among partner pairs. Amplified 16S rRNA genes of bacteria and archaea from a total of 340 skin swabs were analyzed by high-throughput sequencing, and the results demonstrated that cohabitation was significantly associated with microbial community composition, although this association was greatly exceeded by characteristics of body location and individuality. Random forest modeling demonstrated that the partners could be predicted 86% of the time (P < 0.001) based on their skin microbiome profiles, which was always greater than combinations of incorrectly matched partners. Cohabiting couples had the most similar overall microbial skin communities on their feet, according to Bray-Curtis distances. In contrast, thigh microbial communities were strongly associated with biological sex rather than cohabiting partner. Additional factors that were associated with the skin microbiome of specific body locations included the use of skin care products, pet ownership, allergies, and alcohol consumption. These baseline data identified links between the skin microbiome and daily interactions among cohabiting individuals, adding to known factors that shape the human microbiome and, by extension, its relation to human health. IMPORTANCE Our work characterizes the influence of cohabitation as a factor influencing the composition of the skin microbiome. Although the body site and sampled individual were stronger influences than other factors collected as metadata in this study, we show that modeling of detected microbial taxa can help with correct identifications of cohabiting partners based on skin microbiome profiles using machine learning approaches. These results show that a cohabiting partner can significantly influence our microbiota. Follow-up studies will be important for investigating the implications of shared microbiota on dermatological health and the contributions of cohabiting parents to the microbiome profiles of their infants.}, } @article {pmid28761934, year = {2017}, author = {Edlund, A and Garg, N and Mohimani, H and Gurevich, A and He, X and Shi, W and Dorrestein, PC and McLean, JS}, title = {Metabolic Fingerprints from the Human Oral Microbiome Reveal a Vast Knowledge Gap of Secreted Small Peptidic Molecules.}, journal = {mSystems}, volume = {2}, number = {4}, pages = {}, doi = {10.1128/mSystems.00058-17}, pmid = {28761934}, issn = {2379-5077}, support = {R01 DE023810/DE/NIDCR NIH HHS/United States ; R01 DE026186/DE/NIDCR NIH HHS/United States ; K99 DE024543/DE/NIDCR NIH HHS/United States ; R00 DE024543/DE/NIDCR NIH HHS/United States ; P41 GM103484/GM/NIGMS NIH HHS/United States ; R01 DE020102/DE/NIDCR NIH HHS/United States ; R01 GM095373/GM/NIGMS NIH HHS/United States ; }, abstract = {Recent research indicates that the human microbiota play key roles in maintaining health by providing essential nutrients, providing immune education, and preventing pathogen expansion. Processes underlying the transition from a healthy human microbiome to a disease-associated microbiome are poorly understood, partially because of the potential influences from a wide diversity of bacterium-derived compounds that are illy defined. Here, we present the analysis of peptidic small molecules (SMs) secreted from bacteria and viewed from a temporal perspective. Through comparative analysis of mass spectral profiles from a collection of cultured oral isolates and an established in vitro multispecies oral community, we found that the production of SMs both delineates a temporal expression pattern and allows discrimination between bacterial isolates at the species level. Importantly, the majority of the identified molecules were of unknown identity, and only ~2.2% could be annotated and classified. The catalogue of bacterially produced SMs we obtained in this study reveals an undiscovered molecular world for which compound isolation and ecosystem testing will facilitate a better understanding of their roles in human health and disease. IMPORTANCE Metabolomics is the ultimate tool for studies of microbial functions under any specific set of environmental conditions (D. S. Wishart, Nat Rev Drug Discov 45:473-484, 2016, https://doi.org/10.1038/nrd.2016.32). This is a great advance over studying genes alone, which only inform about metabolic potential. Approximately 25,000 compounds have been chemically characterized thus far; however, the richness of metabolites such as SMs has been estimated to be as high as 1 × 1030 in the biosphere (K. Garber, Nat Biotechnol 33:228-231, 2015, https://doi.org/10.1038/nbt.3161). Our classical, one-at-a-time activity-guided approach to compound identification continues to find the same known compounds and is also incredibly tedious, which represents a major bottleneck for global SM identification. These challenges have prompted new developments of databases and analysis tools that provide putative classifications of SMs by mass spectral alignments to already characterized tandem mass spectrometry spectra and databases containing structural information (e.g., PubChem and AntiMarin). In this study, we assessed secreted peptidic SMs (PSMs) from 27 oral bacterial isolates and a complex oral in vitro biofilm community of >100 species by using the Global Natural Products Social molecular Networking and the DEREPLICATOR infrastructures, which are methodologies that allow automated and putative annotation of PSMs. These approaches enabled the identification of an untapped resource of PSMs from oral bacteria showing species-unique patterns of secretion with putative matches to known bioactive compounds.}, } @article {pmid28760934, year = {2017}, author = {Spinler, JK and Auchtung, J and Brown, A and Boonma, P and Oezguen, N and Ross, CL and Luna, RA and Runge, J and Versalovic, J and Peniche, A and Dann, SM and Britton, RA and Haag, A and Savidge, TC}, title = {Next-Generation Probiotics Targeting Clostridium difficile through Precursor-Directed Antimicrobial Biosynthesis.}, journal = {Infection and immunity}, volume = {85}, number = {10}, pages = {}, doi = {10.1128/IAI.00303-17}, pmid = {28760934}, issn = {1098-5522}, support = {P30 DK056338/DK/NIDDK NIH HHS/United States ; U01 AI124290/AI/NIAID NIH HHS/United States ; U19 AI090872/AI/NIAID NIH HHS/United States ; UL1 TR000071/TR/NCATS NIH HHS/United States ; R21 DK096323/DK/NIDDK NIH HHS/United States ; }, mesh = {Anti-Bacterial Agents/*biosynthesis/pharmacology/therapeutic use ; Bacterial Proteins/genetics ; Clostridium Infections/immunology/*prevention & control/therapy ; Clostridium difficile/drug effects/*growth & development ; Drug Discovery/methods ; Drug Resistance, Bacterial ; Feces/microbiology ; Fermentation ; Gastrointestinal Microbiome ; Glyceraldehyde/*analogs & derivatives/metabolism/pharmacology/therapeutic use ; Glycerol/*administration & dosage/immunology/metabolism ; Humans ; Lactobacillus reuteri/*metabolism ; Metabolomics ; *Probiotics ; Propane/*metabolism/pharmacology/therapeutic use ; Vancomycin/pharmacology ; }, abstract = {Integration of antibiotic and probiotic therapy has the potential to lessen the public health burden of antimicrobial-associated diseases. Clostridium difficile infection (CDI) represents an important example where the rational design of next-generation probiotics is being actively pursued to prevent disease recurrence. Because intrinsic resistance to clinically relevant antibiotics used to treat CDI (vancomycin, metronidazole, and fidaxomicin) is a desired trait in such probiotic species, we screened several bacteria and identified Lactobacillus reuteri to be a promising candidate for adjunct therapy. Human-derived L. reuteri bacteria convert glycerol to the broad-spectrum antimicrobial compound reuterin. When supplemented with glycerol, strains carrying the pocR gene locus were potent reuterin producers, with L. reuteri 17938 inhibiting C. difficile growth at a level on par with the level of growth inhibition by vancomycin. Targeted pocR mutations and complementation studies identified reuterin to be the precursor-induced antimicrobial agent. Pathophysiological relevance was demonstrated when the codelivery of L. reuteri with glycerol was effective against C. difficile colonization in complex human fecal microbial communities, whereas treatment with either glycerol or L. reuteri alone was ineffective. A global unbiased microbiome and metabolomics analysis independently confirmed that glycerol precursor delivery with L. reuteri elicited changes in the composition and function of the human microbial community that preferentially targets C. difficile outgrowth and toxicity, a finding consistent with glycerol fermentation and reuterin production. Antimicrobial resistance has thus been successfully exploited in the natural design of human microbiome evasion of C. difficile, and this method may provide a prototypic precursor-directed probiotic approach. Antibiotic resistance and substrate bioavailability may therefore represent critical new determinants of probiotic efficacy in clinical trials.}, } @article {pmid28759253, year = {2017}, author = {Scriba, TJ and Carpenter, C and Pro, SC and Sidney, J and Musvosvi, M and Rozot, V and Seumois, G and Rosales, SL and Vijayanand, P and Goletti, D and Makgotlho, E and Hanekom, W and Hatherill, M and Peters, B and Sette, A and Arlehamn, CSL}, title = {Differential Recognition of Mycobacterium tuberculosis-Specific Epitopes as a Function of Tuberculosis Disease History.}, journal = {American journal of respiratory and critical care medicine}, volume = {196}, number = {6}, pages = {772-781}, doi = {10.1164/rccm.201706-1208OC}, pmid = {28759253}, issn = {1535-4970}, support = {HHSN272200900044C/AI/NIAID NIH HHS/United States ; U19 AI111211/AI/NIAID NIH HHS/United States ; U19 AI118626/AI/NIAID NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antigens, Bacterial/*blood ; Child ; Child, Preschool ; Cohort Studies ; Enzyme-Linked Immunospot Assay ; Epitopes, T-Lymphocyte/*blood ; Female ; Humans ; Infant ; Male ; Middle Aged ; Mycobacterium tuberculosis/*genetics/*immunology ; Tuberculosis/*immunology ; Young Adult ; }, abstract = {RATIONALE: Individuals with a history of tuberculosis (TB) disease are at elevated risk of disease recurrence. The underlying cause is not known, but one explanation is that previous disease results in less-effective immunity against Mycobacterium tuberculosis (Mtb).

OBJECTIVES: We hypothesized that the repertoire of Mtb-derived epitopes recognized by T cells from individuals with latent Mtb infection differs as a function of previous diagnosis of active TB disease.

METHODS: T-cell responses to peptide pools in samples collected from an adult screening and an adolescent validation cohort were measured by IFN-γ enzyme-linked immunospot assay or intracellular cytokine staining.

MEASUREMENTS AND MAIN RESULTS: We identified a set of "type 2" T-cell epitopes that were recognized at 10-fold-lower levels in Mtb-infected individuals with a history of TB disease less than 6 years ago than in those without previous TB. By contrast, "type 1" epitopes were recognized equally well in individuals with or without previous TB. The differential epitope recognition was not due to differences in HLA class II binding, memory phenotypes, or gene expression in the responding T cells. Instead, "TB disease history-sensitive" type 2 epitopes were significantly (P < 0.0001) more homologous to sequences from bacteria found in the human microbiome than type 1 epitopes.

CONCLUSIONS: Preferential loss of T-cell reactivity to Mtb epitopes that are homologous to bacteria in the microbiome in persons with previous TB disease may reflect long-term effects of antibiotic TB treatment on the microbiome.}, } @article {pmid28754707, year = {2017}, author = {Peixoto, RJM and Alves, ES and Wang, M and Ferreira, RBR and Granato, A and Han, J and Gill, H and Jacobson, K and Lobo, LA and Domingues, RMCP and Borchers, CH and Davies, JE and Finlay, BB and Antunes, LCM}, title = {Repression of Salmonella host cell invasion by aromatic small molecules from the human fecal metabolome.}, journal = {Applied and environmental microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1128/AEM.01148-17}, pmid = {28754707}, issn = {1098-5336}, abstract = {The human microbiome is a collection of microorganisms that inhabit every surface of the body that is exposed to the environment, generally coexisting peacefully with their host. These microbes have important functions such as the production of vitamins, maturation of the immune system and protection against pathogens. We have previously shown that a small-molecule extract from the human fecal microbiome has a strong repressive effect on Salmonella enterica serovar Typhimurium host cell invasion by modulating the expression of genes involved in this process. Here, we describe the characterization of this biological activity. Using a series of purification methods, we obtained fractions with biological activity and characterized them by mass spectrometry. These experiments revealed an abundance of aromatic compounds in the bioactive fraction. Selected compounds were obtained from commercial sources and tested with respect to their ability to repress the expression of hilA, the gene encoding the master regulator of invasion genes in Salmonella We found that the aromatic compound 3,4-dimethylbenzoic acid acts as a strong inhibitor of hilA expression as well as invasion of cultured host cells by Salmonella Future studies should reveal the molecular details of this phenomenon, such as the signaling cascades involved in sensing this bioactive molecule.Importance Microbes constantly sense and adapt to their environment. Often, this is achieved through the production and sensing of small extracellular molecules. The human body is colonized by complex communities of microbes, and, given their biological and chemical diversity, these ecosystems represent a platform where the production and sensing of molecules occurs. In previous work, we showed that small molecules produced by microbes from the human gut can significantly impair the virulence of the enteric pathogen Salmonella enterica Here, we describe a specific compound from the human gut that produces this same effect. The results from this work not only shed light on an important biological phenomenon occurring in our bodies but also may represent an opportunity to develop drugs that can target these small-molecule interactions to protect us from enteric infections and other diseases.}, } @article {pmid28750103, year = {2017}, author = {Van Leuvenhaege, C and Vandelannoote, K and Affolabi, D and Portaels, F and Sopoh, G and de Jong, BC and Eddyani, M and Meehan, CJ}, title = {Bacterial diversity in Buruli ulcer skin lesions: Challenges in the clinical microbiome analysis of a skin disease.}, journal = {PloS one}, volume = {12}, number = {7}, pages = {e0181994}, doi = {10.1371/journal.pone.0181994}, pmid = {28750103}, issn = {1932-6203}, mesh = {Adolescent ; Adult ; Aged ; Buruli Ulcer/*microbiology ; Case-Control Studies ; Child ; Humans ; *Microbiota/drug effects ; Middle Aged ; Mycobacterium ulcerans/classification ; Oxygen/pharmacology ; Phylogeny ; Principal Component Analysis ; Skin/*microbiology/*pathology ; Staining and Labeling ; Young Adult ; }, abstract = {BACKGROUND: Buruli ulcer (BU) is an infectious disease caused by Mycobacterium ulcerans and considered the third most prevalent mycobacterial disease in humans. Secondary bacterial infections in open BU lesions are the main cause of pain, delayed healing and systemic illness, resulting in prolonged hospital stay. Thus, understanding the diversity of bacteria, termed the microbiome, in these open lesions is important for proper treatment. However, adequately studying the human microbiome in a clinical setting can prove difficult when investigating a neglected tropical skin disease due to its rarity and the setting.

Using 16S rRNA sequencing, we determined the microbial composition of 5 BU lesions, 3 non-BU lesions and 3 healthy skin samples. Although no significant differences in diversity were found between BU and non-BU lesions, the former were characterized by an increase of Bacteroidetes compared to the non-BU wounds and the BU lesions also contained significantly more obligate anaerobes. With this molecular-based study, we were also able to detect bacteria that were missed by culture-based methods in previous BU studies.

CONCLUSIONS/SIGNIFICANCE: Our study suggests that BU may lead to changes in the skin bacterial community within the lesions. However, in order to determine if such changes hold true across all BU cases and are either a cause or consequence of a specific wound environment, further microbiome studies are necessary. Such skin microbiome analysis requires large sample sizes and lesions from the same body site in many patients, both of which can be difficult for a rare disease. Our study proposes a pipeline for such studies and highlights several drawbacks that must be considered if microbiome analysis is to be utilized for neglected tropical diseases.}, } @article {pmid28745328, year = {2018}, author = {Ganesh, BP and Hall, A and Ayyaswamy, S and Nelson, JW and Fultz, R and Major, A and Haag, A and Esparza, M and Lugo, M and Venable, S and Whary, M and Fox, JG and Versalovic, J}, title = {Diacylglycerol kinase synthesized by commensal Lactobacillus reuteri diminishes protein kinase C phosphorylation and histamine-mediated signaling in the mammalian intestinal epithelium.}, journal = {Mucosal immunology}, volume = {11}, number = {2}, pages = {380-393}, doi = {10.1038/mi.2017.58}, pmid = {28745328}, issn = {1935-3456}, support = {U01 CA170930/CA/NCI NIH HHS/United States ; P30 ES002109/ES/NIEHS NIH HHS/United States ; R01 OD011141/OD/NIH HHS/United States ; UH3 DK083990/DK/NIDDK NIH HHS/United States ; P30 DK056338/DK/NIDDK NIH HHS/United States ; T32 OD010978/OD/NIH HHS/United States ; R01 AT004326/AT/NCCIH NIH HHS/United States ; }, abstract = {Lactobacillus reuteri 6475 (Lr) of the human microbiome synthesizes histamine and can suppress inflammation via type 2 histamine receptor (H2R) activation in the mammalian intestine. Gut microbes such as Lr promote H2R signaling and may suppress H1R proinflammatory signaling pathways in parallel by unknown mechanisms. In this study, we identified a soluble bacterial enzyme known as diacylglycerol kinase (Dgk) from Lr that is secreted into the extracellular milieu and presumably into the intestinal lumen. DgK diminishes diacylglycerol (DAG) quantities in mammalian cells by promoting its metabolic conversion and causing reduced protein kinase C phosphorylation (pPKC) as a net effect in mammalian cells. We demonstrated that histamine synthesized by gut microbes (Lr) activates both mammalian H1R and H2R, but Lr-derived Dgk suppresses the H1R signaling pathway. Phospho-PKC and IκBα were diminished within the intestinal epithelium of mice and humans treated by wild-type (WT) Lr, but pPKC and IκBα were not decreased in treatment with ΔdgkA Lr. Mucosal IL-6 and systemic interleukin (IL)-1α, eotaxin, and granulocyte colony-stimulating factor (G-CSF) were suppressed in WT Lr, but not in ΔdgkA Lr colonized mice. Collectively, the commensal microbe Lr may act as a "microbial antihistamine" by suppressing intestinal H1R-mediated proinflammatory responses via diminished pPKC-mediated mammalian cell signaling.}, } @article {pmid28742161, year = {2017}, author = {Rendueles, O and Garcia-Garcerà, M and Néron, B and Touchon, M and Rocha, EPC}, title = {Abundance and co-occurrence of extracellular capsules increase environmental breadth: Implications for the emergence of pathogens.}, journal = {PLoS pathogens}, volume = {13}, number = {7}, pages = {e1006525}, doi = {10.1371/journal.ppat.1006525}, pmid = {28742161}, issn = {1553-7374}, mesh = {Bacteria/classification/genetics/*metabolism/pathogenicity ; Bacterial Capsules/*metabolism ; Bacterial Infections/*microbiology ; Bacterial Proteins/genetics/metabolism ; Genome, Bacterial ; Humans ; Phylogeny ; Virulence ; }, abstract = {Extracellular capsules constitute the outermost layer of many bacteria, are major virulence factors, and affect antimicrobial therapies. They have been used as epidemiological markers and recently became vaccination targets. Despite the efforts to biochemically serotype capsules in a few model pathogens, little is known of their taxonomic and environmental distribution. We developed, validated, and made available a computational tool, CapsuleFinder, to identify capsules in genomes. The analysis of over 2500 prokaryotic genomes, accessible in a database, revealed that ca. 50% of them-including Archaea-encode a capsule. The Wzx/Wzy-dependent capsular group was by far the most abundant. Surprisingly, a fifth of the genomes encode more than one capsule system-often from different groups-and their non-random co-occurrence suggests the existence of negative and positive epistatic interactions. To understand the role of multiple capsules, we queried more than 6700 metagenomes for the presence of species encoding capsules and showed that their distribution varied between environmental categories and, within the human microbiome, between body locations. Species encoding capsules, and especially those encoding multiple capsules, had larger environmental breadths than the other species. Accordingly, capsules were more frequent in environmental bacteria than in pathogens and, within the latter, they were more frequent among facultative pathogens. Nevertheless, capsules were frequent in clinical samples, and were usually associated with fast-growing bacteria with high infectious doses. Our results suggest that capsules increase the environmental range of bacteria and make them more resilient to environmental perturbations. Capsules might allow opportunistic pathogens to profit from empty ecological niches or environmental perturbations, such as those resulting from antibiotic therapy, to colonize the host. Capsule-associated virulence might thus be a by-product of environmental adaptation. Understanding the role of capsules in natural environments might enlighten their function in pathogenesis.}, } @article {pmid28737021, year = {2017}, author = {Brüssow, H}, title = {Infection therapy: the problem of drug resistance - and possible solutions.}, journal = {Microbial biotechnology}, volume = {10}, number = {5}, pages = {1041-1046}, doi = {10.1111/1751-7915.12777}, pmid = {28737021}, issn = {1751-7915}, mesh = {Animals ; Anti-Bacterial Agents/administration & dosage ; Bacteria/*drug effects/genetics/metabolism/virology ; Bacterial Infections/drug therapy/microbiology/*therapy ; Bacteriophages/physiology ; Biological Therapy ; Drug Resistance, Bacterial ; Humans ; Probiotics/administration & dosage ; }, abstract = {The rising antibiotic resistance in major bacterial pathogens together with the breakdown of the antibiotic discovery platform creates a critical situation for infection therapy. Recent developments reviving new antibiotic discovery from defining chemical rules for membrane-passing compounds to isolation chips for soil bacteria and exploring the human microbiome for antibiotic-producing bacteria are discussed. The potential of bacteriocins, tailocins, phage lysins, phages, probiotics and commensal blends as alternatives to antibiotics is evaluated.}, } @article {pmid28730144, year = {2017}, author = {Yu, G and Torres, J and Hu, N and Medrano-Guzman, R and Herrera-Goepfert, R and Humphrys, MS and Wang, L and Wang, C and Ding, T and Ravel, J and Taylor, PR and Abnet, CC and Goldstein, AM}, title = {Molecular Characterization of the Human Stomach Microbiota in Gastric Cancer Patients.}, journal = {Frontiers in cellular and infection microbiology}, volume = {7}, number = {}, pages = {302}, doi = {10.3389/fcimb.2017.00302}, pmid = {28730144}, issn = {2235-2988}, mesh = {Adult ; Aged ; Bacteria/classification/genetics/*isolation & purification ; China ; Female ; *Gastrointestinal Microbiome ; Helicobacter pylori/classification/genetics/isolation & purification ; Humans ; Male ; Mexico ; Middle Aged ; Stomach/*microbiology ; Stomach Neoplasms/*microbiology ; Young Adult ; }, abstract = {Helicobacter pylori (Hp) is the primary cause of gastric cancer but we know little of its relative abundance and other microbes in the stomach, especially at the time of gastric cancer diagnosis. Here we characterized the taxonomic and derived functional profiles of gastric microbiota in two different sets of gastric cancer patients, and compared them with microbial profiles in other body sites. Paired non-malignant and tumor tissues were sampled from 160 gastric cancer patients with 80 from China and 80 from Mexico. The 16S rRNA gene V3-V4 region was sequenced using MiSeq platform for taxonomic profiles. PICRUSt was used to predict functional profiles. Human Microbiome Project was used for comparison. We showed that Hp is the most abundant member of gastric microbiota in both Chinese and Mexican samples (51 and 24%, respectively), followed by oral-associated bacteria. Taxonomic (phylum-level) profiles of stomach microbiota resembled oral microbiota, especially when the Helicobacter reads were removed. The functional profiles of stomach microbiota, however, were distinct from those found in other body sites and had higher inter-subject dissimilarity. Gastric microbiota composition did not differ by Hp colonization status or stomach anatomic sites, but did differ between paired non-malignant and tumor tissues in either Chinese or Mexican samples. Our study showed that Hp is the dominant member of the non-malignant gastric tissue microbiota in many gastric cancer patients. Our results provide insights on the gastric microbiota composition and function in gastric cancer patients, which may have important clinical implications.}, } @article {pmid28728057, year = {2017}, author = {Clarke, TH and Gomez, A and Singh, H and Nelson, KE and Brinkac, LM}, title = {Integrating the microbiome as a resource in the forensics toolkit.}, journal = {Forensic science international. Genetics}, volume = {30}, number = {}, pages = {141-147}, doi = {10.1016/j.fsigen.2017.06.008}, pmid = {28728057}, issn = {1878-0326}, mesh = {Forensic Genetics/*methods ; *High-Throughput Nucleotide Sequencing ; Humans ; Microbiota/*genetics ; Postmortem Changes ; RNA, Ribosomal, 16S ; Sequence Analysis, RNA ; }, abstract = {The introduction of DNA fingerprinting to forensic science rapidly expanded the available evidence that could be garnered from a crime scene and used in court cases. Next generation sequencing technologies increased available genetic data that could be used as evidence by orders of magnitude, and as such, significant additional genetic information is now available for use in forensic science. This includes DNA from the bacteria that live in and on humans, known as the human microbiome. Next generation sequencing of the human microbiome demonstrates that its bacterial DNA can be used to uniquely identify an individual, provide information about their life and behavioral patterns, determine the body site where a sample came from, and estimate postmortem intervals. Bacterial samples from the environment and objects can also be leveraged to address similar questions about the individual(s) who interacted with them. However, the applications of this new field in forensic sciences raises concerns on current methods used in sample processing, including sample collection, storage, and the statistical power of published studies. These areas of human microbiome research need to be fully addressed before microbiome data can become a regularly incorporated evidence type and routine procedure of the forensic toolkit. Here, we summarize information on the current status of microbiome research as applies to the forensic field, the mathematical models used to make predictions, and the possible legal and practical difficulties that can limit the application of microbiomes in forensic science.}, } @article {pmid28725438, year = {2017}, author = {Lusi, EA and Patrissi, T and Guarascio, P}, title = {Nickel-resistant bacteria isolated in human microbiome.}, journal = {New microbes and new infections}, volume = {19}, number = {}, pages = {67-70}, doi = {10.1016/j.nmni.2017.06.001}, pmid = {28725438}, issn = {2052-2975}, abstract = {Nickel-resistant bacteria have been isolated so far only in contaminated soils and wastewaters polluted with different industrial sources. The aim of our study was to determine if nickel-resistant bacteria could also be isolated from human samples. In this brief communication, we describe how we were able to isolate human bacterial strains that grew without oxygen and in the presence of high concentrations of nickel. The identification was made by phenotypic and genetic techniques. The bacterial sequences have been deposited in the NCBI database repository. Our finding shows that there are several different heavy-metal-tolerant bacteria in humans that should be considered for further studies.}, } @article {pmid28719406, year = {2017}, author = {Maier, KJ and alʼAbsi, M}, title = {Toward a Biopsychosocial Ecology of the Human Microbiome, Brain-Gut Axis, and Health.}, journal = {Psychosomatic medicine}, volume = {79}, number = {8}, pages = {947-957}, doi = {10.1097/PSY.0000000000000515}, pmid = {28719406}, issn = {1534-7796}, mesh = {Brain/*physiology ; Gastrointestinal Microbiome/*physiology ; Humans ; Signal Transduction/*physiology ; }, abstract = {OBJECTIVE: Rapidly expanding insights into the human microbiome and health suggest that Western medicine is poised for significant evolution, or perhaps revolution-this while medicine continues on a trajectory from reductionism to a biopsychosocial (BPS) paradigm recognizing biological, psychological, and social influences on health. The apparent sensitivity of the microbiota to perturbations across BPS domains suggests that a broad and inclusive framework is needed to develop applicable knowledge in this emerging area. We outline an ecological framework of the human microbiome by extending the BPS concept to better incorporate environmental and human factors as members of a global, dynamic set of systems that interact over time.

METHODS: We conducted a selective literature review across disciplines to integrate microbiome research into a BPS framework.

RESULTS: The microbiome can be understood in terms of ecological systems encompassing BPS domains at four levels: (a) immediate (molecular, genetic, and neural processes), (b) proximal (physiology, emotion, social integration), (c) intermediate (built environments, behaviors, societal practices), and (d) distal (physical environments, attitudes, and broad cultural, economic, and political factors). The microbiota and host are thus understood in terms of their immediate interactions and the more distal physical and social arenas in which they participate.

CONCLUSIONS: A BPS ecological paradigm encourages replicable, generalizable, and interdisciplinary/transdisciplinary research and practices that take into account the vast influences on the human microbiome that may otherwise be overlooked or understood out of context. It also underscores the importance of sustainable bioenvironmental, psychological, and social systems that broadly support microbial, neural, and general health.}, } @article {pmid28719264, year = {2017}, author = {Wood, MR and Yu, EA and Mehta, S}, title = {The Human Microbiome in the Fight Against Tuberculosis.}, journal = {The American journal of tropical medicine and hygiene}, volume = {96}, number = {6}, pages = {1274-1284}, doi = {10.4269/ajtmh.16-0581}, pmid = {28719264}, issn = {1476-1645}, support = {T32 DK007158/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Disease Models, Animal ; *Gastrointestinal Microbiome ; Gastrointestinal Tract/microbiology ; Humans ; Immunomodulation ; Lung/microbiology ; Mycobacterium tuberculosis ; Tuberculosis/microbiology/*therapy ; Tuberculosis, Pulmonary/microbiology/*therapy ; }, abstract = {AbstractThe human microbiome is an intriguing potentially modifiable risk factor in our arsenal against Mycobacterium tuberculosis, the leading infectious disease killer globally. Previous studies have shown associations between the human microbiome and pulmonary disease states; however, etiological links between the microbiome and tuberculosis (TB) infection or disease remain unclear. Immunomodulatory roles of the microbiome may prove to be a critical asset in the host response against TB, including in preventing TB infection, reducing progression from latency, mitigating disease severity, and lowering the incidence of drug resistance and coinfections. This review examined the associations between TB and the gut and lung microbiome. Eight studies were identified through a PubMed database search, including one animal study (N = 1), case report (N = 1), and case-control studies (N = 6). TB infection and disease were associated with reduced gastrointestinal microbial diversity in a murine model and human case report. Sputum microbial diversity differed by TB status in case-control studies, although some reported heterogeneous findings. Current evidence suggests that the gut and lung microbiome are associated with TB infection and disease. However, as studies are limited, etiological and longitudinal research is needed to determine clinical relevance.}, } @article {pmid28718274, year = {2017}, author = {Suárez Moya, A}, title = {[Microbiome and next generation sequencing].}, journal = {Revista espanola de quimioterapia : publicacion oficial de la Sociedad Espanola de Quimioterapia}, volume = {30}, number = {5}, pages = {305-311}, pmid = {28718274}, issn = {1988-9518}, mesh = {Biodiversity ; DNA, Bacterial/*analysis ; *High-Throughput Nucleotide Sequencing ; Humans ; Microbiota/*genetics ; Sequence Analysis, DNA/*methods ; }, abstract = {The human microbiome is an internal ecosystem that refers to the community of microorganisms that populate the human body. These microorganisms are essential to support his health, because the interaction between the host immune system and microorganisms, provide the host with protection against pathogens, and contributes to the preservation of health. Bacteriological culture has been the basis for traditional microbiology; however, most of the bacterial forms observed in nature cannot be isolated with laboratory culture methods. At present, metagenomic applies a suite of genomic technologies, where the microorganisms are identified by their genomic fingerprint. The 16S rRNA subunit is considered as the universal target for bacterial identification from DNA with the aid of sequencing. Sanger sequencing technology had a great impact on the first generation sequencing due to its simplicity and precision. Platforms high-throughput known as second generation secuencing technologies are capable to generate hundreds of thousands of sequence reactions in a faster and economic way. However, thanks to the third generation sequencing the greatest advances in nanotechnology have been made. Using the reference gene, the massive sequencing techniques and bioinformatics tools used for the data processing, there has been an important development of the human microbiome, achieving an unprecedented detail level on the taxonomy and microbial function. This has meant an authentic revolution not only in their knowledge but also in their involvement in the health or illness of the human being.}, } @article {pmid28713344, year = {2017}, author = {Poppleton, DI and Duchateau, M and Hourdel, V and Matondo, M and Flechsler, J and Klingl, A and Beloin, C and Gribaldo, S}, title = {Outer Membrane Proteome of Veillonella parvula: A Diderm Firmicute of the Human Microbiome.}, journal = {Frontiers in microbiology}, volume = {8}, number = {}, pages = {1215}, doi = {10.3389/fmicb.2017.01215}, pmid = {28713344}, issn = {1664-302X}, abstract = {Veillonella parvula is a biofilm-forming commensal found in the lungs, vagina, mouth, and gastro-intestinal tract of humans, yet it may develop into an opportunistic pathogen. Furthermore, the presence of Veillonella has been associated with the development of a healthy immune system in infants. Veillonella belongs to the Negativicutes, a diverse clade of bacteria that represent an evolutionary enigma: they phylogenetically belong to Gram-positive (monoderm) Firmicutes yet maintain an outer membrane (OM) with lipopolysaccharide similar to classic Gram-negative (diderm) bacteria. The OMs of Negativicutes have unique characteristics including the replacement of Braun's lipoprotein by OmpM for tethering the OM to the peptidoglycan. Through phylogenomic analysis, we have recently provided bioinformatic annotation of the Negativicutes diderm cell envelope. We showed that it is a unique type of envelope that was present in the ancestor of present-day Firmicutes and lost multiple times independently in this phylum, giving rise to the monoderm architecture; however, little experimental data is presently available for any Negativicutes cell envelope. Here, we performed the first experimental proteomic characterization of the cell envelope of a diderm Firmicute, producing an OM proteome of V. parvula. We initially conducted a thorough bioinformatics analysis of all 1,844 predicted proteins from V. parvula DSM 2008's genome using 12 different localization prediction programs. These results were complemented by protein extraction with surface exposed (SE) protein tags and by subcellular fractionation, both of which were analyzed by liquid chromatography tandem mass spectrometry. The merging of proteomics and bioinformatics results allowed identification of 78 OM proteins. These include a number of receptors for TonB-dependent transport, the main component of the BAM system for OM protein biogenesis (BamA), the Lpt system component LptD, which is responsible for insertion of LPS into the OM, and several copies of the major OmpM protein. The annotation of V. parvula's OM proteome markedly extends previous inferences on the nature of the cell envelope of Negativicutes, including the experimental evidence of a BAM/TAM system for OM protein biogenesis and of a complete Lpt system for LPS transport to the OM. It also provides important information on the role of OM components in the lifestyle of Veillonella, such as a possible gene cluster for O-antigen synthesis and a large number of adhesins. Finally, many OM hypothetical proteins were identified, which are priority targets for further characterization.}, } @article {pmid28711782, year = {2017}, author = {Blum, HE}, title = {The human microbiome.}, journal = {Advances in medical sciences}, volume = {62}, number = {2}, pages = {414-420}, doi = {10.1016/j.advms.2017.04.005}, pmid = {28711782}, issn = {1898-4002}, mesh = {Bacteria ; *Bacterial Physiological Phenomena ; Biodiversity ; *Disease ; Humans ; *Microbiota ; }, abstract = {Until recently, human microbiology was based on the identification of single microbes, such as bacteria, fungi and viruses, frequently isolated from patients with acute or chronic infections. Novel culture-independent molecular biochemical analyses (genomics, transcriptomics, proteomics, metabolomics) allow today to detect and classify the diverse microorganisms in a given ecosystem (microbiota), such as the gastrointestinal tract, the skin, the airway system, the urogenital tract and others, and to assess all genomes in these ecosystems (microbiome) as well as their gene products. These analyses revealed that each individual has its own microbiota that plays a role in health and disease. In addition, they greatly contributed to the recent advances in the understanding of the pathogenesis of a wide range of human diseases. It is to be expected that these new insights will translate into diagnostic, therapeutic and preventive measures in the context of personalized/precision medicine.}, } @article {pmid28706916, year = {2017}, author = {Ruiz-Rodriguez, M and Rello, J}, title = {Human microbiome in respiratory diseases.}, journal = {Annals of translational medicine}, volume = {5}, number = {12}, pages = {248}, doi = {10.21037/atm.2017.06.21}, pmid = {28706916}, issn = {2305-5839}, } @article {pmid28704437, year = {2017}, author = {Lai, PS and Allen, JG and Hutchinson, DS and Ajami, NJ and Petrosino, JF and Winters, T and Hug, C and Wartenberg, GR and Vallarino, J and Christiani, DC}, title = {Impact of environmental microbiota on human microbiota of workers in academic mouse research facilities: An observational study.}, journal = {PloS one}, volume = {12}, number = {7}, pages = {e0180969}, doi = {10.1371/journal.pone.0180969}, pmid = {28704437}, issn = {1932-6203}, support = {K23 ES023700/ES/NIEHS NIH HHS/United States ; P30 ES000002/ES/NIEHS NIH HHS/United States ; T32 ES007069/ES/NIEHS NIH HHS/United States ; }, mesh = {Air Pollutants, Occupational/analysis ; Animal Technicians ; Animals ; Bacteria/*classification/genetics ; DNA, Bacterial/genetics ; Endotoxins/*genetics ; Humans ; Medical Laboratory Personnel ; Mice ; *Microbiota ; Mouth/microbiology ; Nose/microbiology ; Occupational Exposure/*classification ; RNA, Ribosomal, 16S/*genetics ; Skin/microbiology ; }, abstract = {OBJECTIVES: To characterize the microbial environment of workers in academic mouse research facilities using endotoxin, 16S qPCR, and 16S amplicon sequencing. To determine whether the work microbiome contributes to the human microbiome of workers.

METHODS: We performed area air sampling from the animal rooms, dirty, middle, and setup cage wash locations in four academic mouse research facilities. 10 workers in the dirty cage wash area underwent personal air sampling as well as repeated collection of nasal, oral, and skin samples before and after the work shift. Environmental samples underwent measurement of endotoxin, mouse allergen, bacteria copy number via 16S qPCR, and microbial identification via 16S rDNA sequencing. 16S rDNA sequencing was also performed on human samples before and after the work shift. SourceTracker was used to identify the contribution of the work microbiome to the human microbiome.

RESULTS: Median endotoxin levels ranged from undetectable to 1.0 EU/m3. Significant differences in mouse allergen levels, bacterial copy number, microbial richness, and microbial community structure were identified between animal, dirty, middle, and setup cage wash locations. Endotoxin levels had only a moderate correlation with microbial composition. Location within a facility was a stronger predictor of microbial community composition (R2 = 0.41, p = 0.002) than facility. The contribution of the work microbiome to the pre-shift human microbiome of workers was estimated to be 0.1 ± 0.1% for the oral microbiome; 3.1 ± 1.9% for the nasal microbiome; and 3.0 ± 1.5% for the skin microbiome.

CONCLUSIONS: The microbial environment of academic animal care facilities varies significantly by location rather than facility. Endotoxin is not a proxy for assessment of environmental microbial exposures using 16S qPCR or 16S rDNA sequencing. The work microbiome contributes to the composition of the nasal and skin microbiome of workers; the clinical implications of this observation should be further studied.}, } @article {pmid28702202, year = {2017}, author = {Diop, A and Raoult, D and Fenollar, F and Fournier, PE}, title = {'Khoudiadiopia massiliensis' gen. nov., sp. nov., strain Marseille-P2746TT, a new bacterial genus isolated from the female genital tract.}, journal = {New microbes and new infections}, volume = {19}, number = {}, pages = {60-61}, doi = {10.1016/j.nmni.2017.06.002}, pmid = {28702202}, issn = {2052-2975}, abstract = {We report the main characteristics of 'Khoudiadiopia massiliensis' gen. nov., sp. nov., strain Marseille-P2746T (= CSUR P2746), a new member of the Peptoniphilaceae family isolated from a vaginal swab of a patient suffering from bacterial vaginosis.}, } @article {pmid28696940, year = {2017}, author = {Quagliarello, A and De Fanti, S and Giuliani, C and Abondio, P and Serventi, P and Sarno, S and Sazzini, M and Luiselli, D}, title = {Multiple selective events at the PRDM16 functional pathway shaped adaptation of western European populations to different climate conditions.}, journal = {Journal of anthropological sciences = Rivista di antropologia : JASS}, volume = {95}, number = {}, pages = {235-247}, doi = {10.4436/JASS.95011}, pmid = {28696940}, issn = {2037-0644}, mesh = {Adaptation, Biological/*genetics ; Body Temperature Regulation/genetics ; *Climate ; DNA-Binding Proteins/*genetics ; Europe ; European Continental Ancestry Group/genetics ; Haplotypes/genetics ; Humans ; Polymorphism, Single Nucleotide/genetics ; Selection, Genetic/*genetics ; Transcription Factors/*genetics ; }, abstract = {Several studies highlighted the role of climate in shaping many human evolutionary processes. This occurred even in relatively recent times, having affected various human phenotypic traits, among which metabolic processes that orchestrate absorption and accumulation of substances to maintain energy homeostasis, that is critical for the survival of individuals in high energy-expenditure environments. To date, most researches have focalized on detection of climatic influence on SNPs' frequency in populations exposed to extreme environmental conditions or by comparing variation patterns between populations from different continents. In this study, we instead explored the genetic background of distinct western European human groups at loci involved in nutritional and thermoregulation processes, to test whether patterns of differential local adaptation to environmental conditions could be appreciated also at a lower geographical scale. Taking advantage from the 1000 Genomes Project data, genetic information for 21 genes involved in nutritional and thermoregulation processes was analysed for three western European populations. The applied Anthropological Genetics methods pointed to appreciable differentiation between the examined groups especially for the PRDM16 gene. Moreover, several neutrality tests suggested that balancing selection has acted on different regions of the gene in people from Great Britain, as well as that more recent positive selection could have also targeted some PRDM16 SNPs in Finn and Italian populations. These series of adaptive footprints are plausibly related to climate variability in both ancient and relatively recent times. Since this locus is involved in thermoregulation mechanisms and adipogenesis, local adaptations mediated by a pathway related to the brown adipose tissue activity could have evolved in response to changing cold temperature exposures of such populations.}, } @article {pmid28690602, year = {2017}, author = {Gupta, VK and Paul, S and Dutta, C}, title = {Geography, Ethnicity or Subsistence-Specific Variations in Human Microbiome Composition and Diversity.}, journal = {Frontiers in microbiology}, volume = {8}, number = {}, pages = {1162}, doi = {10.3389/fmicb.2017.01162}, pmid = {28690602}, issn = {1664-302X}, abstract = {One of the fundamental issues in the microbiome research is characterization of the healthy human microbiota. Recent studies have elucidated substantial divergences in the microbiome structure between healthy individuals from different race and ethnicity. This review provides a comprehensive account of such geography, ethnicity or life-style-specific variations in healthy microbiome at five major body habitats-Gut, Oral-cavity, Respiratory Tract, Skin, and Urogenital Tract (UGT). The review focuses on the general trend in the human microbiome evolution-a gradual transition in the gross compositional structure along with a continual decrease in diversity of the microbiome, especially of the gut microbiome, as the human populations passed through three stages of subsistence like foraging, rural farming and industrialized urban western life. In general, gut microbiome of the hunter-gatherer populations is highly abundant with Prevotella, Proteobacteria, Spirochaetes, Clostridiales, Ruminobacter etc., while those of the urban communities are often enriched in Bacteroides, Bifidobacterium, and Firmicutes. The oral and skin microbiome are the next most diverse among different populations, while respiratory tract and UGT microbiome show lesser variations. Higher microbiome diversity is observed for oral-cavity in hunter-gatherer group with higher prevalence of Haemophilus than agricultural group. In case of skin microbiome, rural and urban Chinese populations show variation in abundance of Trabulsiella and Propionibacterium. On the basis of published data, we have characterized the core microbiota-the set of genera commonly found in all populations, irrespective of their geographic locations, ethnicity or mode of subsistence. We have also identified the major factors responsible for geography-based alterations in microbiota; though it is not yet clear which factor plays a dominant role in shaping the microbiome-nature or nurture, host genetics or his environment. Some of the geographical/racial variations in microbiome structure have been attributed to differences in host genetics and innate/adaptive immunity, while in many other cases, cultural/behavioral features like diet, hygiene, parasitic load, environmental exposure etc. overshadow genetics. The ethnicity or population-specific variations in human microbiome composition, as reviewed in this report, question the universality of the microbiome-based therapeutic strategies and recommend for geographically tailored community-scale approaches to microbiome engineering.}, } @article {pmid28676754, year = {2017}, author = {Emery, DC and Shoemark, DK and Batstone, TE and Waterfall, CM and Coghill, JA and Cerajewska, TL and Davies, M and West, NX and Allen, SJ}, title = {16S rRNA Next Generation Sequencing Analysis Shows Bacteria in Alzheimer's Post-Mortem Brain.}, journal = {Frontiers in aging neuroscience}, volume = {9}, number = {}, pages = {195}, doi = {10.3389/fnagi.2017.00195}, pmid = {28676754}, issn = {1663-4365}, abstract = {The neurological deterioration associated with Alzheimer's disease (AD), involving accumulation of amyloid-beta peptides and neurofibrillary tangles, is associated with evident neuroinflammation. This is now seen to be a significant contributor to pathology. Recently the tenet of the privileged status of the brain, regarding microbial compromise, has been questioned, particularly in terms of neurodegenerative diseases. It is now being considered that microbiological incursion into the central nervous system could be either an initiator or significant contributor to these. This is a novel study using 16S ribosomal gene-specific Next generation sequencing (NGS) of extracted brain tissue. A comparison was made of the bacterial species content of both frozen and formaldehyde fixed sections of a small cohort of Alzheimer-affected cases with those of cognitively unimpaired (normal). Our findings suggest an increase in bacterial populations in Alzheimer brain tissue compared with normal.}, } @article {pmid28669823, year = {2017}, author = {Wefers, D and Cavalcante, JJV and Schendel, RR and Deveryshetty, J and Wang, K and Wawrzak, Z and Mackie, RI and Koropatkin, NM and Cann, I}, title = {Biochemical and Structural Analyses of Two Cryptic Esterases in Bacteroides intestinalis and their Synergistic Activities with Cognate Xylanases.}, journal = {Journal of molecular biology}, volume = {429}, number = {16}, pages = {2509-2527}, doi = {10.1016/j.jmb.2017.06.017}, pmid = {28669823}, issn = {1089-8638}, mesh = {Amino Acid Sequence ; Bacteroides/*enzymology ; Caffeic Acids/metabolism ; Chromatography, Gel ; Coumaric Acids/metabolism ; Crystallography, X-Ray ; Esterases/*chemistry/*metabolism ; Kinetics ; Magnetic Resonance Spectroscopy ; Molecular Sequence Data ; Protein Conformation ; Protein Multimerization ; Sequence Alignment ; Substrate Specificity ; Xylans/metabolism ; Xylosidases/*metabolism ; }, abstract = {Arabinoxylans are constituents of the human diet. Although not utilizable by the human host, they can be fermented by colonic bacteria. The arabinoxylan backbone is decorated with arabinose side chains that may be substituted with ferulic acid, thus limiting depolymerization to fermentable sugars. We investigated the polypeptides encoded by two genes upregulated during growth of the colonic bacterium Bacteroides intestinalis on wheat arabinoxylan. The recombinant proteins, designated BiFae1A and BiFae1B, were functionally assigned esterase activities. Both enzymes were active on acetylated substrates, although each showed a higher ferulic acid esterase activity on methyl-ferulate. BiFae1A showed a catalytic efficiency of 12mM s-1 on para-nitrophenyl-acetate, and on methyl-ferulate, the value was 27 times higher. BiFae1B showed low catalytic efficiencies for both substrates. Furthermore, the two enzymes released ferulic acid from various structural elements, and NMR spectroscopy indicated complete de-esterification of arabinoxylan oligosaccharides from wheat bran. BiFae1A is a tetramer based on the crystal structure, whereas BiFae1B is a dimer in solution based on size exclusion chromatography. The structure of BiFae1A was solved to 1.98Å resolution, and two tetramers were observed in the asymmetric unit. A flexible loop that may act as a hinge over the active site and likely coordinates critical interactions with the substrate was prominent in BiFae1A. Sequence alignments of the esterase domains in BiFae1B with the feruloyl esterase from Clostridium thermocellum suggest that both domains lack the flexible hinge in BiFae1A, an observation that may partly provide a molecular basis for the differences in activities in the two esterases.}, } @article {pmid28667752, year = {2017}, author = {Madhoolika, B and Anil Kumar, NV and Balaji, S}, title = {In vitro analysis of 4-methylumbelliferone as a sole carbon source for Lactobacillus helveticus 2126.}, journal = {Letters in applied microbiology}, volume = {65}, number = {3}, pages = {249-255}, doi = {10.1111/lam.12772}, pmid = {28667752}, issn = {1472-765X}, mesh = {Carbon/metabolism ; Culture Media/metabolism ; Humans ; Hymecromone/*metabolism ; Lactobacillus helveticus/genetics/growth & development/*metabolism ; Probiotics/metabolism ; }, abstract = {In the recent years, 4-methylumbelliferone (4-MU) has been gaining importance, both as an anti-cancer agent and as a dietary supplement. The aim of this study was to determine the effectiveness of 4-MU as a carbon source for potential probiotic bacteria Lactobacillus helveticus 2126. For this purpose, a series of plate assays and infrared spectroscopy (FTIR) were used for 4-MU before and after the treatment with L. helveticus 2126. The plate assays indicated an initial inhibition followed by utilization of 4-MU that stimulated bacterial growth. A significant shift was observed in the FTIR peaks, which also have suggested possible extracellular activity of the bacteria for 4-MU utilization.

4-Methylumbelliferone (4-MU) is a widely used chloretic and is currently under research for treating colon cancer. Preliminary studies suggest that it has the potential to be used as an effective and sustainable prebiotic for the human microbiome, as it can be naturally obtained from plants. This manuscript describes the effectiveness of 4-MU as a carbon source for the probiotic bacteria Lactobacillus helveticus. Our study also suggests the role of bacterial superoxide dismutase in transforming 4-MU as a possible prebiotic for the human microbiome.}, } @article {pmid28659968, year = {2017}, author = {Sandoval-Motta, S and Aldana, M and Martínez-Romero, E and Frank, A}, title = {The Human Microbiome and the Missing Heritability Problem.}, journal = {Frontiers in genetics}, volume = {8}, number = {}, pages = {80}, doi = {10.3389/fgene.2017.00080}, pmid = {28659968}, issn = {1664-8021}, abstract = {The "missing heritability" problem states that genetic variants in Genome-Wide Association Studies (GWAS) cannot completely explain the heritability of complex traits. Traditionally, the heritability of a phenotype is measured through familial studies using twins, siblings and other close relatives, making assumptions on the genetic similarities between them. When this heritability is compared to the one obtained through GWAS for the same traits, a substantial gap between both measurements arise with genome wide studies reporting significantly smaller values. Several mechanisms for this "missing heritability" have been proposed, such as epigenetics, epistasis, and sequencing depth. However, none of them are able to fully account for this gap in heritability. In this paper we provide evidence that suggests that in order for the phenotypic heritability of human traits to be broadly understood and accounted for, the compositional and functional diversity of the human microbiome must be taken into account. This hypothesis is based on several observations: (A) The composition of the human microbiome is associated with many important traits, including obesity, cancer, and neurological disorders. (B) Our microbiome encodes a second genome with nearly a 100 times more genes than the human genome, and this second genome may act as a rich source of genetic variation and phenotypic plasticity. (C) Human genotypes interact with the composition and structure of our microbiome, but cannot by themselves explain microbial variation. (D) Microbial genetic composition can be strongly influenced by the host's behavior, its environment or by vertical and horizontal transmissions from other hosts. Therefore, genetic similarities assumed in familial studies may cause overestimations of heritability values. We also propose a method that allows the compositional and functional diversity of our microbiome to be incorporated to genome wide association studies.}, } @article {pmid28658154, year = {2017}, author = {Ashton, JJ and Colquhoun, CM and Cleary, DW and Coelho, T and Haggarty, R and Mulder, I and Batra, A and Afzal, NA and Beattie, RM and Scott, KP and Ennis, S}, title = {16S sequencing and functional analysis of the fecal microbiome during treatment of newly diagnosed pediatric inflammatory bowel disease.}, journal = {Medicine}, volume = {96}, number = {26}, pages = {e7347}, doi = {10.1097/MD.0000000000007347}, pmid = {28658154}, issn = {1536-5964}, mesh = {Adolescent ; Biodiversity ; Child ; Fatty Acids, Volatile/analysis ; Feces/chemistry/*microbiology ; Female ; Gastrointestinal Microbiome/*genetics ; Humans ; Inflammatory Bowel Diseases/genetics/metabolism/*microbiology/*therapy ; Longitudinal Studies ; Male ; Prospective Studies ; RNA, Bacterial/*analysis ; RNA, Ribosomal, 16S/*analysis ; Sequence Analysis, RNA ; Siblings ; Treatment Outcome ; }, abstract = {The human microbiome is of considerable interest to pediatric inflammatory bowel disease (PIBD) researchers with 1 potential mechanism for disease development being aberrant immune handling of the intestinal bacteria. This study analyses the fecal microbiome through treatment in newly diagnosed PIBD patients and compares to cohabiting siblings where possible. Patients were recruited on clinical suspicion of PIBD before diagnosis. Treatment-naïve fecal samples were collected, with further samples at 2 and 6 weeks into treatment. Samples underwent 16S ribosomal ribonucleic acid (RNA) gene sequencing and short-chain fatty acids (SCFAs) analysis, results were analyzed using quantitative-insights-into-microbial-ecology. Six PIBD patients were included in the cohort: 4 Crohn disease (CD), 1 ulcerative colitis (UC), 1 inflammatory bowel disease (IBD) unclassified, and median age 12.6 (range 10-15.1 years); 3 patients had an unaffected healthy sibling recruited. Microbial diversity (observed species/Chao1/Shannon diversity) was reduced in treatment-naïve patients compared to siblings and patients in remission. Principal coordinate analysis using Bray-Curtis dissimilarity and UniFrac revealed microbial shifts in CD over the treatment course. In treatment-naïve PIBD, there was reduction in functional ability for amino acid metabolism and carbohydrate handling compared to controls (P = .038) and patients in remission (P = .027). Metabolic function returned to normal after remission was achieved. SCFA revealed consistent detection of lactate in treatment-naïve samples. This study adds in-depth 16S rRNA sequencing analysis on a small longitudinal cohort to the literature and includes sibling controls and patients with UC/IBD unclassified. It highlights the initial dysbiosis, reduced diversity, altered functional potential, and subsequent shifts in bacteria from diagnosis over time to remission.}, } @article {pmid28648295, year = {2017}, author = {Caradonna, T and Marangi, M and Del Chierico, F and Ferrari, N and Reddel, S and Bracaglia, G and Normanno, G and Putignani, L and Giangaspero, A}, title = {Detection and prevalence of protozoan parasites in ready-to-eat packaged salads on sale in Italy.}, journal = {Food microbiology}, volume = {67}, number = {}, pages = {67-75}, doi = {10.1016/j.fm.2017.06.006}, pmid = {28648295}, issn = {1095-9998}, mesh = {Cryptosporidium/genetics/growth & development/*isolation & purification ; Cyclospora/genetics/growth & development/*isolation & purification ; DNA, Protozoan ; Fast Foods/*parasitology ; Food Contamination/analysis/*statistics & numerical data ; Italy ; Toxoplasma/genetics/growth & development/*isolation & purification ; Vegetables/*parasitology ; }, abstract = {To investigate the prevalence of protozoan contamination by Giardia duodenalis, Cryptosporidium spp., Toxoplasma gondii and Cyclospora cayetanensis, in 'ready to eat' (RTE) salads on sale in Italy, 648 packages were purchased from industrial and local brands. Nine individual packages from each brand were collected per month, pooled and subjected to microscopy and molecular analyses. Microscopic examination of 864 slides detected Cryptosporidium spp. but also Blastocystis hominis and Dientamoeba fragilis. Molecular tools identified G. duodenalis assemblage A, Cryptosporidium parvum and Cryptosporidium ubiquitum, T. gondii Type I and C. cayetanensis. B. hominis and D. fragilis were also molecularly confirmed. The overall prevalence of each protozoan species was 0.6% for G. duodenalis, 0.8% for T. gondii, 0.9% for Cryptosporidium spp., and 1.3% for C. cayetanensis, while prevalence for B. hominis was 0.5% and for D. fragilis 0.2%. Microscopy and/or molecular tools revealed that 4.2% of the samples were contaminated by at least one protozoan species, and 0.6% of samples presented contamination by two protozoan species, with a number of oocysts ranging from 62 to 554 per g of vegetable matter for T. gondii, and 46 to 1.580 for C. cayetanensis. This is Europe's first large-scale study on the presence of protozoans in packaged salads, and shows that RTE sanitation processes do not guarantee a product free from protozoans of fecal origin.}, } @article {pmid28644475, year = {2017}, author = {Benjdia, A and Guillot, A and Ruffié, P and Leprince, J and Berteau, O}, title = {Post-translational modification of ribosomally synthesized peptides by a radical SAM epimerase in Bacillus subtilis.}, journal = {Nature chemistry}, volume = {9}, number = {7}, pages = {698-707}, doi = {10.1038/nchem.2714}, pmid = {28644475}, issn = {1755-4349}, abstract = {Ribosomally synthesized peptides are built out of L-amino acids, whereas D-amino acids are generally the hallmark of non-ribosomal synthetic processes. Here we show that the model bacterium Bacillus subtilis is able to produce a novel type of ribosomally synthesized and post-translationally modified peptide that contains D-amino acids, and which we propose to call epipeptides. We demonstrate that a two [4Fe-4S]-cluster radical S-adenosyl-L-methionine (SAM) enzyme converts L-amino acids into their D-counterparts by catalysing Cα-hydrogen-atom abstraction and using a critical cysteine residue as the hydrogen-atom donor. Unexpectedly, these D-amino acid residues proved to be essential for the activity of a peptide that induces the expression of LiaRS, a major component of the bacterial cell envelope stress-response system. Present in B. subtilis and in several members of the human microbiome, these epipeptides and radical SAM epimerases broaden the landscape of peptidyl structures accessible to living organisms.}, } @article {pmid28632755, year = {2017}, author = {Yost, S and Duran-Pinedo, AE and Krishnan, K and Frias-Lopez, J}, title = {Potassium is a key signal in host-microbiome dysbiosis in periodontitis.}, journal = {PLoS pathogens}, volume = {13}, number = {6}, pages = {e1006457}, doi = {10.1371/journal.ppat.1006457}, pmid = {28632755}, issn = {1553-7374}, mesh = {Bacteria/classification/genetics/*isolation & purification ; Dysbiosis/immunology/*microbiology ; Gingiva/immunology/microbiology ; Humans ; Interleukin-6/immunology ; *Microbiota ; Mouth/immunology/*microbiology ; Periodontitis/immunology/*microbiology ; Phylogeny ; Potassium/*immunology ; Tumor Necrosis Factor-alpha/immunology ; beta-Defensins/immunology ; }, abstract = {Dysbiosis, or the imbalance in the structural and/or functional properties of the microbiome, is at the origin of important infectious inflammatory diseases such as inflammatory bowel disease (IBD) and periodontal disease. Periodontitis is a polymicrobial inflammatory disease that affects a large proportion of the world's population and has been associated with a wide variety of systemic health conditions, such as diabetes, cardiovascular and respiratory diseases. Dysbiosis has been identified as a key element in the development of the disease. However, the precise mechanisms and environmental signals that lead to the initiation of dysbiosis in the human microbiome are largely unknown. In a series of previous in vivo studies using metatranscriptomic analysis of periodontitis and its progression we identified several functional signatures that were highly associated with the disease. Among them, potassium ion transport appeared to be key in the process of pathogenesis. To confirm its importance we performed a series of in vitro experiments, in which we demonstrated that potassium levels a increased the virulence of the oral community as a whole and at the same time altering the immune response of gingival epithelium, increasing the production of TNF-α and reducing the expression of IL-6 and the antimicrobial peptide human β-defensin 3 (hBD-3). These results indicate that levels of potassium in the periodontal pocket could be an important element in of dysbiosis in the oral microbiome. They are a starting point for the identification of key environmental signals that modify the behavior of the oral microbiome from a symbiotic community to a dysbiotic one.}, } @article {pmid28626612, year = {2017}, author = {DeBruyn, JM and Hauther, KA}, title = {Postmortem succession of gut microbial communities in deceased human subjects.}, journal = {PeerJ}, volume = {5}, number = {}, pages = {e3437}, doi = {10.7717/peerj.3437}, pmid = {28626612}, issn = {2167-8359}, abstract = {The human microbiome has demonstrated an importance for the health and functioning in living individuals. However, the fate of the microbiome after death is less understood. In addition to a better understanding of microbe-mediated decomposition processes, postmortem succession of human-associated microbial communities has been suggested as a possible forensic tool for estimating time since death, or postmortem interval (PMI). The objective of our study was to document postmortem changes in human gut bacterial communities. Gut microflora were repeatedly sampled from the caeca of cadavers as they decayed under natural environmental conditions. 16S rRNA gene amplicon sequencing revealed that over time, bacterial richness significantly increased (rs = 0.449) while diversity decreased (rs = - 0.701). The composition of gut bacterial communities changed in a similar manner over time towards a common decay community. OTUs belonging to Bacteroidales (Bacteroides, Parabacteroides) significantly declined while Clostridiales (Clostridium, Anaerosphaera) and the fly-associated Gammaproteobacteria Ignatzschineria and Wohlfahrtiimonas increased. Our examination of human caeca microflora in decomposing cadavers adds to the growing literature on postmortem microbial communities, which will ultimately contribute to a better understanding of decomposition processes.}, } @article {pmid28615076, year = {2017}, author = {Tolonen, AC and Xavier, RJ}, title = {Dissecting the human microbiome with single-cell genomics.}, journal = {Genome medicine}, volume = {9}, number = {1}, pages = {56}, doi = {10.1186/s13073-017-0448-7}, pmid = {28615076}, issn = {1756-994X}, support = {P30 DK043351/DK/NIDDK NIH HHS/United States ; U54 DK102557/DK/NIDDK NIH HHS/United States ; }, mesh = {Bacteria/*genetics ; *Genome, Bacterial ; Genomics/*methods ; Humans ; *Microbiota ; Sequence Analysis, DNA/*methods ; }, abstract = {Recent advances in genome sequencing of single microbial cells enable the assignment of functional roles to members of the human microbiome that cannot currently be cultured. This approach can reveal the genomic basis of phenotypic variation between closely related strains and can be applied to the targeted study of immunogenic bacteria in disease.}, } @article {pmid28600901, year = {2017}, author = {Jatzlauk, G and Bartel, S and Heine, H and Schloter, M and Krauss-Etschmann, S}, title = {Influences of environmental bacteria and their metabolites on allergies, asthma, and host microbiota.}, journal = {Allergy}, volume = {72}, number = {12}, pages = {1859-1867}, doi = {10.1111/all.13220}, pmid = {28600901}, issn = {1398-9995}, mesh = {Age Factors ; Animals ; Asthma/epidemiology/*etiology/prevention & control ; Bacteria/*immunology/metabolism ; Environment ; Environmental Exposure/*adverse effects ; Host-Pathogen Interactions/*immunology ; Humans ; Hypersensitivity/epidemiology/*etiology/prevention & control ; Immunomodulation ; *Microbiota ; Models, Animal ; Pulmonary Alveoli/immunology/metabolism ; Respiratory Mucosa/immunology/microbiology ; }, abstract = {The prevalence of allergic diseases and asthma has dramatically increased over the last decades, resulting in a high burden for patients and healthcare systems. Thus, there is an unmet need to develop preventative strategies for these diseases. Epidemiological studies show that reduced exposure to environmental bacteria in early life (eg, birth by cesarean section, being formula-fed, growing up in an urban environment or with less contact to various persons) is associated with an increased risk to develop allergies and asthma later in life. Conversely, a reduced risk for asthma is consistently found in children growing up on traditional farms, thereby being exposed to a wide spectrum of microbes. However, clinical studies with bacteria to prevent allergic diseases are still rare and to some extent contradicting. A detailed mechanistic understanding of how environmental microbes influence the development of the human microbiome and the immune system is important to enable the development of novel preventative approaches that are based on the early modulation of the host microbiota and immunity. In this mini-review, we summarize current knowledge and experimental evidence for the potential of bacteria and their metabolites to be used for the prevention of asthma and allergic diseases.}, } @article {pmid28594642, year = {2017}, author = {McElroy, KG and Chung, SY and Regan, M}, title = {CE: Health and the Human Microbiome: A Primer for Nurses.}, journal = {The American journal of nursing}, volume = {117}, number = {7}, pages = {24-30}, doi = {10.1097/01.NAJ.0000520917.73358.99}, pmid = {28594642}, issn = {1538-7488}, mesh = {*Curriculum ; Education, Nursing, Continuing ; Evidence-Based Nursing/*education ; Female ; Gastrointestinal Tract/*microbiology ; Humans ; Microbiota/*physiology ; Nursing Staff/*education ; Vagina/*microbiology ; }, abstract = {: The profound impact of the human microbiome on health makes it imperative that nurses understand the basic structures and functions of the various microbial communities. In studying the human microbiome, advances in DNA and RNA sequencing technology offer benefits over traditional culture-based methods. Such technology has permitted more thorough investigations of microbial communities, particularly those of the gastrointestinal (GI) and female reproductive tracts. Although individual variations exist, each site exhibits distinct compositions. The diverse GI microbiota aid in digestion, mood regulation, and vitamin synthesis. While many factors affect the composition and functions of the GI microbiota, diet likely exerts the strongest influence. Vaginal microbiota tend to be less diverse, and mainly serve to protect women from infection. The composition of the vaginal microbiota is influenced by sexual activity, hygienic practices, medications, smoking, and other factors. Our increasing knowledge about the structures and functions of the GI and vaginal microbiota allows nurses to provide targeted, evidence-based education and care for various populations.}, } @article {pmid28587343, year = {2017}, author = {Dong, T and Feng, Q and Liu, F and Chang, LK and Zhou, X and Han, M and Tian, X and Zhong, N and Liu, S}, title = {Alteration of stomach microbiota compositions in the progression of gastritis induces nitric oxide in gastric cell.}, journal = {Experimental and therapeutic medicine}, volume = {13}, number = {6}, pages = {2793-2800}, doi = {10.3892/etm.2017.4373}, pmid = {28587343}, issn = {1792-0981}, abstract = {Atrophic gastritis is considered to be an antecedent to intestinal metaplasia and gastric cancer. A previous study identified that Helicobacter pylori was absent at the severe atrophic gastritis stage, and alterations in the gastric microbial composition resembled those in gastric cancer. To explore the role of the bacteria absence of H. pylori in gastric carcinogenesis, in the current study, we compared the microbiota of clinically collected H. pylori-free gastric fluids from 30 patients with non-atrophic gastritis (N) and 22 patients with severe atrophic gastritis (S). We estimated the bacterial loads in the N and S groups by colony counting in culture agar as well as by measuring the concentration of the extracted DNA. The results showed a significant increase in bacterial load in patients with atrophic gastritis in comparison to non-atrophic gastritis. Then, we analyzed the microbial communities of the gastric fluids from all 52 patients using high-throughput sequencing of 16S rRNA amplicons. The Chao 1, Shannon and Simpson diversity indexes demonstrated that the bacterial richness and diversity were not significantly different between the N and S groups. Moreover, principal component analysis illustrated that the microbiomes from the S group were more scattered. Microbiota composition analysis showed that the entire dataset was clustered into 27 phyla, 61 classes, 106 orders, 177 families, 292 genera and 121 species. At the genus level, only the abundance of Prevotella was significantly different between the N and S groups. Further analysis showed that all the higher taxonomic categories were significantly different between the N and S groups. To assess the effects of the metabolic products of Prevotella spp. on gastric cell physiology, we treated the human gastric epithelial cell line AGS with acetic acid and monitored nitric oxide (NO) production. The results showed that acetic acid at low concentrations (0.5 and 5 µM) significantly inhibited AGS cells to secrete NO compared to phosphate buffer saline-treated control cells. These results suggest that the microbiota in non-atrophic gastritis may influence gastric epithelial cell physiology.}, } @article {pmid28578872, year = {2017}, author = {Pollet, RM and D'Agostino, EH and Walton, WG and Xu, Y and Little, MS and Biernat, KA and Pellock, SJ and Patterson, LM and Creekmore, BC and Isenberg, HN and Bahethi, RR and Bhatt, AP and Liu, J and Gharaibeh, RZ and Redinbo, MR}, title = {An Atlas of β-Glucuronidases in the Human Intestinal Microbiome.}, journal = {Structure (London, England : 1993)}, volume = {25}, number = {7}, pages = {967-977.e5}, doi = {10.1016/j.str.2017.05.003}, pmid = {28578872}, issn = {1878-4186}, support = {P30 ES010126/ES/NIEHS NIH HHS/United States ; T32 GM008570/GM/NIGMS NIH HHS/United States ; P30 CA016086/CA/NCI NIH HHS/United States ; R01 CA161879/CA/NCI NIH HHS/United States ; R01 HL094463/HL/NHLBI NIH HHS/United States ; R01 CA207416/CA/NCI NIH HHS/United States ; T32 DK007737/DK/NIDDK NIH HHS/United States ; U01 GM102137/GM/NIGMS NIH HHS/United States ; R01 CA098468/CA/NCI NIH HHS/United States ; }, mesh = {Bacterial Proteins/*chemistry/classification/genetics/metabolism ; *Gastrointestinal Microbiome ; Glucuronidase/*chemistry/classification/genetics/metabolism ; Humans ; }, abstract = {Microbiome-encoded β-glucuronidase (GUS) enzymes play important roles in human health by metabolizing drugs in the gastrointestinal (GI) tract. The numbers, types, and diversity of these proteins in the human GI microbiome, however, remain undefined. We present an atlas of GUS enzymes comprehensive for the Human Microbiome Project GI database. We identify 3,013 total and 279 unique microbiome-encoded GUS proteins clustered into six unique structural categories. We assign their taxonomy, assess cellular localization, reveal the inter-individual variability within the 139 individuals sampled, and discover 112 novel microbial GUS enzymes. A representative in vitro panel of the most common GUS proteins by read abundances highlights structural and functional variabilities within the family, including their differential processing of smaller glucuronides and larger carbohydrates. These data provide a sequencing-to-molecular roadmap for examining microbiome-encoded enzymes essential to human health.}, } @article {pmid28578396, year = {2017}, author = {Daisley, BA and Trinder, M and McDowell, TW and Welle, H and Dube, JS and Ali, SN and Leong, HS and Sumarah, MW and Reid, G}, title = {Neonicotinoid-induced pathogen susceptibility is mitigated by Lactobacillus plantarum immune stimulation in a Drosophila melanogaster model.}, journal = {Scientific reports}, volume = {7}, number = {1}, pages = {2703}, doi = {10.1038/s41598-017-02806-w}, pmid = {28578396}, issn = {2045-2322}, abstract = {Pesticides are used extensively in food production to maximize crop yields. However, neonicotinoid insecticides exert unintentional toxicity to honey bees (Apis mellifera) that may partially be associated with massive population declines referred to as colony collapse disorder. We hypothesized that imidacloprid (common neonicotinoid; IMI) exposure would make Drosophila melanogaster (an insect model for the honey bee) more susceptible to bacterial pathogens, heat stress, and intestinal dysbiosis. Our results suggested that the immune deficiency (Imd) pathway is necessary for D. melanogaster survival in response to IMI toxicity. IMI exposure induced alterations in the host-microbiota as noted by increased indigenous Acetobacter and Lactobacillus spp. Furthermore, sub-lethal exposure to IMI resulted in decreased D. melanogaster survival when simultaneously exposed to bacterial infection and heat stress (37 °C). This coincided with exacerbated increases in TotA and Dpt (Imd downstream pro-survival and antimicrobial genes, respectively) expression compared to controls. Supplementation of IMI-exposed D. melanogaster with Lactobacillus plantarum ATCC 14917 mitigated survival deficits following Serratia marcescens (bacterial pathogen) septic infection. These findings support the insidious toxicity of neonicotinoid pesticides and potential for probiotic lactobacilli to reduce IMI-induced susceptibility to infection.}, } @article {pmid28572753, year = {2017}, author = {Brooks, JP and Buck, GA and Chen, G and Diao, L and Edwards, DJ and Fettweis, JM and Huzurbazar, S and Rakitin, A and Satten, GA and Smirnova, E and Waks, Z and Wright, ML and Yanover, C and Zhou, YH}, title = {Changes in vaginal community state types reflect major shifts in the microbiome.}, journal = {Microbial ecology in health and disease}, volume = {28}, number = {1}, pages = {1303265}, doi = {10.1080/16512235.2017.1303265}, pmid = {28572753}, issn = {0891-060X}, abstract = {Background: Recent studies of various human microbiome habitats have revealed thousands of bacterial species and the existence of large variation in communities of microorganisms in the same habitats across individual human subjects. Previous efforts to summarize this diversity, notably in the human gut and vagina, have categorized microbiome profiles by clustering them into community state types (CSTs). The functional relevance of specific CSTs has not been established. Objective: We investigate whether CSTs can be used to assess dynamics in the microbiome. Design: We conduct a re-analysis of five sequencing-based microbiome surveys derived from vaginal samples with repeated measures. Results: We observe that detection of a CST transition is largely insensitive to choices in methods for normalization or clustering. We find that healthy subjects persist in a CST for two to three weeks or more on average, while those with evidence of dysbiosis tend to change more often. Changes in CST can be gradual or occur over less than one day. Upcoming CST changes and switches to high-risk CSTs can be predicted with high accuracy in certain scenarios. Finally, we observe that presence of Gardnerella vaginalis is a strong predictor of an upcoming CST change. Conclusion: Overall, our results show that the CST concept is useful for studying microbiome dynamics.}, } @article {pmid28561849, year = {2017}, author = {Adnani, N and Rajski, SR and Bugni, TS}, title = {Symbiosis-inspired approaches to antibiotic discovery.}, journal = {Natural product reports}, volume = {34}, number = {7}, pages = {784-814}, doi = {10.1039/c7np00009j}, pmid = {28561849}, issn = {1460-4752}, support = {R01 GM104192/GM/NIGMS NIH HHS/United States ; R01 GM107557/GM/NIGMS NIH HHS/United States ; U19 AI109673/AI/NIAID NIH HHS/United States ; U19 TW009872/TW/FIC NIH HHS/United States ; }, mesh = {Animals ; *Anti-Bacterial Agents ; Bacteria/metabolism ; Biological Evolution ; Fungi/physiology ; Humans ; Molecular Structure ; Multigene Family ; Plants/metabolism ; Symbiosis/*physiology ; }, abstract = {Covering: 2010 up to 2017Life on Earth is characterized by a remarkable abundance of symbiotic and highly refined relationships among life forms. Defined as any kind of close, long-term association between two organisms, symbioses can be mutualistic, commensalistic or parasitic. Historically speaking, selective pressures have shaped symbioses in which one organism (typically a bacterium or fungus) generates bioactive small molecules that impact the host (and possibly other symbionts); the symbiosis is driven fundamentally by the genetic machineries available to the small molecule producer. The human microbiome is now integral to the most recent chapter in animal-microbe symbiosis studies and plant-microbe symbioses have significantly advanced our understanding of natural products biosynthesis; this also is the case for studies of fungal-microbe symbioses. However, much less is known about microbe-microbe systems involving interspecies interactions. Microbe-derived small molecules (i.e. antibiotics and quorum sensing molecules, etc.) have been shown to regulate transcription in microbes within the same environmental niche, suggesting interspecies interactions whereas, intraspecies interactions, such as those that exploit autoinducing small molecules, also modulate gene expression based on environmental cues. We, and others, contend that symbioses provide almost unlimited opportunities for the discovery of new bioactive compounds whose activities and applications have been evolutionarily optimized. Particularly intriguing is the possibility that environmental effectors can guide laboratory expression of secondary metabolites from "orphan", or silent, biosynthetic gene clusters (BGCs). Notably, many of the studies summarized here result from advances in "omics" technologies and highlight how symbioses have given rise to new anti-bacterial and antifungal natural products now being discovered.}, } @article {pmid28557822, year = {2017}, author = {de Clercq, NC and Frissen, MN and Groen, AK and Nieuwdorp, M}, title = {Gut Microbiota and the Gut-Brain Axis: New Insights in the Pathophysiology of Metabolic Syndrome.}, journal = {Psychosomatic medicine}, volume = {79}, number = {8}, pages = {874-879}, doi = {10.1097/PSY.0000000000000495}, pmid = {28557822}, issn = {1534-7796}, mesh = {Animals ; *Brain/metabolism ; *Gastrointestinal Microbiome ; Humans ; Metabolic Syndrome/immunology/*metabolism/microbiology ; *Signal Transduction ; }, abstract = {OBJECTIVE: Emerging preclinical evidence has shown that the bidirectional signaling between the gastrointestinal (GI) tract and the brain, the so-called gut-brain axis, plays an important role in both host metabolism and behavior. In this review, we discuss the potential mechanisms of the brain-gut axis in relation to the pathophysiology of metabolic syndrome.

METHODS: A selective literature review was conducted to evaluate GI and brain interactions.

RESULTS: Evidence suggests reduced microbial diversity in obesity and metabolic dysregulation. However, findings of microbiota composition in obese individuals are inconsistent, and the investigation of causality between gut microbiota and energy homeostasis is complex because multiple variables contribute to the gut microbiota composition. The microbial metabolites short chain fatty acids are found to exert numerous physiologic effects, including energy homeostasis through the regulation of GI hormones such as cholecystokinin, glucagon-like peptide 1, peptide tyrosine-tyrosine, and leptin. Preclinical studies show that modifying rodents' microbiota through fecal transplantation results in alterations of these GI hormones and subsequently an altered metabolism and behavior. However, whether and to what extent preclinical findings translate to human metabolism is unclear.

CONCLUSIONS: One of the major limitations and challenges in this field of research is interindividual variability of the microbiome. Future research needs to combine recent insights gained into tracking the dynamics of the microbiome as well as the metabolic responses. Furthermore, advanced mapping of the human microbiome is required to investigate the metabolic implications of the gut-brain axis to develop targeted interventions for obesity and metabolic syndrome.}, } @article {pmid28554152, year = {2017}, author = {Bardele, CF and Schultheiß, S and Lynn, DH and Wright, AG and Dominguez-Bello, MG and Obispo, NE}, title = {Aviisotricha hoazini n. gen., n. sp., the Morphology and Molecular Phylogeny of an Anaerobic Ciliate from the Crop of the Hoatzin (Opisthocomus hoazin), the Cow Among the Birds.}, journal = {Protist}, volume = {168}, number = {3}, pages = {335-351}, doi = {10.1016/j.protis.2017.02.002}, pmid = {28554152}, issn = {1618-0941}, mesh = {Anaerobiosis ; Animals ; Birds/*parasitology/physiology ; Ciliophora/*classification/genetics/*physiology/ultrastructure ; Crop, Avian/parasitology/physiology ; Microscopy, Electron, Scanning ; Microscopy, Electron, Transmission ; Sequence Analysis, DNA ; *Symbiosis ; }, abstract = {The hoatzin is the only known avian species that has evolved a foregut fermentation system similar to that of ruminant animals. Due to the closeness of the bird's fermentation chamber, the crop, to the bird's beak it exudes an unpleasant odour; therefore, the hoatzin is called the "cow among the birds". In addition to Eubacteria and Archaea, responsible for digestion of the vegetation they consume, the bird's crop contains a holotrich ciliate, described here for the first time in detail. Cytological staining of this isotrichid-like ciliate with the Chatton-Lwoff and Protargol staining procedures, as well as SEM and TEM, justified the establishment of the new genus Aviisotricha n. gen. with its new type species Aviisotricha hoazini n. gen., n. sp.. Phylogenetic analyses of a portion of the small subunit rRNA gene supported the taxonomic placement of this new genus and species in the family Isotrichidae. Aviisotricha is compared with Balantidium, Dasytricha and Isotricha with special reference to their dorsal brushes, which show similarity to the paralabial organelle of the Entodiniomorphida. The possible phylogenetic origin of Aviisotricha is discussed and a taxonomic revision of the family Isotrichidae is given.}, } @article {pmid28540051, year = {2017}, author = {Chanyi, RM and Craven, L and Harvey, B and Reid, G and Silverman, MJ and Burton, JP}, title = {Faecal microbiota transplantation: Where did it start? What have studies taught us? Where is it going?.}, journal = {SAGE open medicine}, volume = {5}, number = {}, pages = {2050312117708712}, doi = {10.1177/2050312117708712}, pmid = {28540051}, issn = {2050-3121}, abstract = {The composition and activity of microorganisms in the gut, the microbiome, is emerging as an important factor to consider with regard to the treatment of many diseases. Dysbiosis of the normal community has been implicated in inflammatory bowel disease, Crohn's disease, diabetes and, most notoriously, Clostridium difficile infection. In Canada, the leading treatment strategy for recalcitrant C. difficile infection is to receive faecal material which by nature is