Structure, function and diversity of the healthy human microbiome

Author Posting. © The Authors, 2012. This article is posted here by permission of Nature Publishing Group. The definitive version was published in Nature 486 (2012): 207-214, doi:10.1038/nature11234.Studies of the human microbiome have revealed that even healthy individuals differ remarkably in the microbes that occupy habitats such as the gut, skin and vagina. Much of this diversity remains unexplained, although diet, environment, host genetics and early microbial exposure have all been implicated. Accordingly, to characterize the ecology of human-associated microbial communities, the Human Microbiome Project has analysed the largest cohort and set of distinct, clinically relevant body habitats so far. We found the diversity and abundance of each habitat’s signature microbes to vary widely even among healthy subjects, with strong niche specialization both within and among individuals. The project encountered an estimated 81–99% of the genera, enzyme families and community configurations occupied by the healthy Western microbiome. Metagenomic carriage of metabolic pathways was stable among individuals despite variation in community structure, and ethnic/racial background proved to be one of the strongest associations of both pathways and microbes with clinical metadata. These results thus delineate the range of structural and functional configurations normal in the microbial communities of a healthy population, enabling future characterization of the epidemiology, ecology and translational applications of the human microbiome.This research was supported in part by National Institutes of Health grants U54HG004969 to B.W.B.; U54HG003273 to R.A.G.; U54HG004973 to R.A.G., S.K.H. and J.F.P.; U54HG003067 to E.S.Lander; U54AI084844 to K.E.N.; N01AI30071 to R.L.Strausberg; U54HG004968 to G.M.W.; U01HG004866 to O.R.W.; U54HG003079 to R.K.W.; R01HG005969 to C.H.; R01HG004872 to R.K.; R01HG004885 to M.P.; R01HG005975 to P.D.S.; R01HG004908 to Y.Y.; R01HG004900 to M.K.Cho and P. Sankar; R01HG005171 to D.E.H.; R01HG004853 to A.L.M.; R01HG004856 to R.R.; R01HG004877 to R.R.S. and R.F.; R01HG005172 to P. Spicer.; R01HG004857 to M.P.; R01HG004906 to T.M.S.; R21HG005811 to E.A.V.; M.J.B. was supported by UH2AR057506; G.A.B. was supported by UH2AI083263 and UH3AI083263 (G.A.B., C. N. Cornelissen, L. K. Eaves and J. F. Strauss); S.M.H. was supported by UH3DK083993 (V. B. Young, E. B. Chang, F. Meyer, T. M. S., M. L. Sogin, J. M. Tiedje); K.P.R. was supported by UH2DK083990 (J. V.); J.A.S. and H.H.K. were supported by UH2AR057504 and UH3AR057504 (J.A.S.); DP2OD001500 to K.M.A.; N01HG62088 to the Coriell Institute for Medical Research; U01DE016937 to F.E.D.; S.K.H. was supported by RC1DE0202098 and R01DE021574 (S.K.H. and H. Li); J.I. was supported by R21CA139193 (J.I. and D. S. Michaud); K.P.L. was supported by P30DE020751 (D. J. Smith); Army Research Office grant W911NF-11-1-0473 to C.H.; National Science Foundation grants NSF DBI-1053486 to C.H. and NSF IIS-0812111 to M.P.; The Office of Science of the US Department of Energy under Contract No. DE-AC02-05CH11231 for P.S. C.; LANL Laboratory-Directed Research and Development grant 20100034DR and the US Defense Threat Reduction Agency grants B104153I and B084531I to P.S.C.; Research Foundation - Flanders (FWO) grant to K.F. and J.Raes; R.K. is an HHMI Early Career Scientist; Gordon&BettyMoore Foundation funding and institutional funding fromthe J. David Gladstone Institutes to K.S.P.; A.M.S. was supported by fellowships provided by the Rackham Graduate School and the NIH Molecular Mechanisms in Microbial Pathogenesis Training Grant T32AI007528; a Crohn’s and Colitis Foundation of Canada Grant in Aid of Research to E.A.V.; 2010 IBM Faculty Award to K.C.W.; analysis of the HMPdata was performed using National Energy Research Scientific Computing resources, the BluBioU Computational Resource at Rice University

A framework for human microbiome research

A variety of microbial communities and their genes (the microbiome) exist throughout the human body, with fundamental roles in human health and disease. The National Institutes of Health (NIH)-funded Human Microbiome Project Consortium has established a population-scale framework to develop metagenomic protocols, resulting in a broad range of quality-controlled resources and data including standardized methods for creating, processing and interpreting distinct types of high-throughput metagenomic data available to the scientific community. Here we present resources from a population of 242 healthy adults sampled at 15 or 18 body sites up to three times, which have generated 5,177 microbial taxonomic profiles from 16S ribosomal RNA genes and over 3.5 terabases of metagenomic sequence so far. In parallel, approximately 800 reference strains isolated from the human body have been sequenced. Collectively, these data represent the largest resource describing the abundance and variety of the human microbiome, while providing a framework for current and future studies

The effects of different feed additives on bird performance and the gastrointestinal microbiome of Salmonella-challenged broilers

This dataset contain raw sequence data for 16S amplicon microbiome profiling of broilers challenged with Salmonella and fed several different intervention strategies. Files are tar archives containing zipped fastq raw data files for each sample. The metadata sheet described sample prefixes.A 42-day, 60-unit floor pen (10 pens per treatment, 25 birds per pen) Salmonella challenge study was conducted to determine the effects of supplementing broiler diets with virginiamycin (VM); medium chain fatty acids (MCFA); MCFA plus lactic acid (MCFA+LA) and a phytogenic blend (PB). Effects were assessed on bird performance and ileal, cecal, and litter microbiomes in birds challenged with Salmonella Typhimurium. Treatments were compared with a non-inoculated control group (NIC) and a Salmonella-challenged group without feed additives (IC). At days 14, 28, and 42 of age, all bird weights and intake were measured, 20 birds from each treatment were euthanized, and the ceca and ilea of euthanized birds were collected along with grab litter samples from each pen. Bacterial profiling was performed using 16S rRNA amplicon sequencing. Subsequent analyses were performed for measurements of alpha and beta bacterial community diversity, taxonomic classifications, and assessments of bacterial taxa that were shifted as a result of different treatments. At 42 days, body weights and mortality adjusted feed conversions for the UIC were significantly better (P<0.1) than the IC and VM while the MCFA, MCFA+LA and PB treatments were similar to the negative UIC. The Salmonella challenge itself had significant (P<0.01) effects on the bacterial microbiome of all sample types, with the greatest effects observed in the cecal microbiome of the bird. The VM treatment counteracted the effects of the Salmonella challenge on the overall bacterial communities of all sample types (P<0.05). While none of the antibiotic alternative treatments had significant effects on overall bacterial community structure consistent over time, specific bacterial taxa were impacted by several treatments. These included Candidatus Arthromitus (segmented filamentous bacteria), Peptostreptococcus, and Clostridium species. Unique signature taxonomic effects were identified for each treatment type, demonstrating attributes of each feed additive type in contributing to unique effects on the bird microbiota. Overall, this work identifies microbiome modulations conferred by different antibiotic alternatives under a Salmonella challenge.USDA-AFRI Grant nos. 2016-67015-2491

A consistent and predictable commercial broiler chicken bacterial microbiome in antibiotic-free production displays strong correlations with performance

This dataset includes forward and reverse raw sequencing reads for 2,309 broiler chicken gut, respiratory, and litter samples surveyed using 16S amplicon profiling.Defining the baseline bacterial microbiome is critical towards understanding its relationship with health and disease. In broiler chickens, numerous studies have aimed at defining the core microbiome, yet the core and its possible relationships with health and disease have been difficult to define due to lack of study power. Here, the most comprehensive microbiome-based effort to date in commercial broilers was undertaken. The primary goals of this study included understanding what constitutes core in the broiler gastrointestinal, respiratory, and barn environments; how these core players change across age, geography, and time; and which bacterial taxa correlate with enhanced bird performance in antibiotic-free flocks. Using 2,309 samples from 37 different commercial flocks within a vertically integrated broiler system, and metadata from 549 flocks within that system, the baseline bacterial microbiome was defined. The effects of age, sample type, flock, and successive flock cycles were compared, and results indicate a consistent, predictable, age-dependent bacterial microbiome, irrespective of flock. The tracheal bacterial microbiome of broilers was comprehensively defined for the first time, and interestingly, Lactobacillus was the dominant bacterial taxa in the trachea. Numerous bacterial taxa were identified which were strongly correlated with broiler chicken performance, across multiple tissues. While many positively correlated taxa were identified representing targets for future probiotic development, many negatively associated potential pathogens were identified in the absence of clinical disease, indicating subclinical dynamics occurring that impact performance. Overall, this work provides necessary baseline data for the development of effective antibiotic alternatives for sustainable poultry production.USDA-AFRI Grant nos. 2016-67015-24911 and 2015-68004-2313