http://www.hmpdacc.org Recent articles pertaining to the human microbiome http://www.ncbi.nlm.nih.gov/pubmed/19968883 ABSTRACT: As the National Institutes of Health-funded Human Microbiome Project enters its second phase, and as a major part of this project focuses on the human gut microbiome and its effects on human health, it might help us to travel a century back in time and examine how microbiologists dealt with microbiome-related challenges similar to those of the 21st century using the tools of their time. An article by Arthur I. Kendall, published in The Journal of Biological Chemistry in November 1909 (Some observations on the study of the intestinal bacteria J Biol Chem 1909, 6:499-507), offers a visionary insight into many of today's hot research questions. Fri, 25 Dec 2009 05:00:00 GMT http://www.ncbi.nlm.nih.gov/pubmed/19968883 2009-12-25T05:00:00Z http://www.ncbi.nlm.nih.gov/pubmed/19819907 The Human Microbiome Project (HMP), funded as an initiative of the NIH Roadmap for Biomedical Research (http://nihroadmap.nih.gov), is a multi-component community resource. The goals of the HMP are: (1) to take advantage of new, high-throughput technologies to characterize the human microbiome more fully by studying samples from multiple body sites from each of at least 250 "normal" volunteers; (2) to determine whether there are associations between changes in the microbiome and health/disease by studying several different medical conditions; and (3) to provide both a standardized data resource and new technological approaches to enable such studies to be undertaken broadly in the scientific community. The ethical, legal, and social implications of such research are being systematically studied as well. The ultimate objective of the HMP is to demonstrate that there are opportunities to improve human health through monitoring or manipulation of the human microbiome. The history and implementation of this new program are described here. Wed, 02 Dec 2009 05:00:00 GMT http://www.ncbi.nlm.nih.gov/pubmed/19819907 2009-12-02T05:00:00Z http://www.ncbi.nlm.nih.gov/pubmed/19815760 Fri, 09 Oct 2009 04:00:00 GMT http://www.ncbi.nlm.nih.gov/pubmed/19815760 2009-10-09T04:00:00Z http://www.ncbi.nlm.nih.gov/pubmed/19798447 Metagenomic sequencing projects from environments dominated by a small number of species produce genome-wide population samples. We present a two-site composite likelihood estimator of the scaled recombination rate, rho = 2N(e)c, that operates on metagenomic assemblies in which each sequenced fragment derives from a different individual. This new estimator properly accounts for sequencing error, as quantified by per-base quality scores, and missing data, as inferred from the placement of reads in a metagenomic assembly. We apply our estimator to data from a sludge metagenome project to demonstrate how this method will elucidate the rates of exchange of genetic material in natural microbial populations. Surprisingly, for a fixed amount of sequencing, this estimator has lower variance than similar methods that operate on more traditional population genetic samples of comparable size. In addition, we can infer variation in recombination rate across the genome because metagenomic projects sample genetic diversity genome-wide, not just at particular loci. The method itself makes no assumption specific to microbial populations, opening the door for application to any mixed population sample where the number of individuals sampled is much greater than the number of fragments sequenced. Fri, 02 Oct 2009 04:00:00 GMT http://www.ncbi.nlm.nih.gov/pubmed/19798447 2009-10-02T04:00:00Z http://www.ncbi.nlm.nih.gov/pubmed/19491241 Metagenomics is an emerging field focused on characterizing the structures, functions and dynamic operations of microbial communities sampled in their native habitats without the need for culture. Here, we present findings from a 16S rRNA gene sequence- and whole community DNA shotgun sequencing-based analysis of the adult human gut microbiomes of lean and obese mono- and dizygotic twins. Our findings indicate that a core microbiome can be found at the gene level, despite large variation in community membership, and that variations from the core are associated with obesity. These findings have implications for ongoing Human Microbiome Project(s), and highlight important challenges to the field of metagenomics. Tue, 01 Sep 2009 04:00:00 GMT http://www.ncbi.nlm.nih.gov/pubmed/19491241 2009-09-01T04:00:00Z http://www.ncbi.nlm.nih.gov/pubmed/19393196 Studies of autoimmune disease have focused on the characteristics of the identifiable antibodies. But as our knowledge of the genes associated with the disease states expands, we understand that humans must be viewed as superorganisms in which a plethora of bacterial genomes - a metagenome - work in tandem with our own. The NIH has estimated that 90% of the cells in Homo sapiens are microbial and not human in origin. Some of these microbes create metabolites that interfere with the expression of genes associated with autoimmune disease. Thus, we must re-examine how human gene transcription is affected by the plethora of microbial metabolites. We can no longer assume that antibodies generated in autoimmune disease are created solely as autoantibodies to human DNA. Evidence is now emerging that the human microbiota accumulates during a lifetime, and a variety of persistence mechanisms are coming to light. In one model, obstruction of VDR nuclear-receptor-transcription prevents the innate immune system from making key antimicrobials, allowing the microbes to persist. Genes from these microbes must necessarily impact disease progression. Recent efforts to decrease this VDR-perverting microbiota in patients with autoimmune disease have resulted in reversal of autoimmune processes. As the NIH Human Microbiome Project continues to better characterize the human metagenome, new insights into autoimmune pathogenesis are beginning to emerge. Tue, 16 Jun 2009 04:00:00 GMT http://www.ncbi.nlm.nih.gov/pubmed/19393196 2009-06-16T04:00:00Z http://www.ncbi.nlm.nih.gov/pubmed/19480946 The phylogenetic structure of the microbial community residing in a fermentation sample from a production-scale biogas plant fed with maize silage, green rye and liquid manure was analysed by an integrated approach using clone library sequences and metagenome sequence data obtained by 454-pyrosequencing. Sequencing of 109 clones from a bacterial and an archaeal 16S-rDNA amplicon library revealed that the obtained nucleotide sequences are similar but not identical to 16S-rDNA database sequences derived from different anaerobic environments including digestors and bioreactors. Most of the bacterial 16S-rDNA sequences could be assigned to the phylum Firmicutes with the most abundant class Clostridia and to the class Bacteroidetes, whereas most archaeal 16S-rDNA sequences cluster close to the methanogen Methanoculleus bourgensis. Further sequences of the archaeal library most probably represent so far non-characterised species within the genus Methanoculleus. A similar result derived from phylogenetic analysis of mcrA clone sequences. The mcrA gene product encodes the alpha-subunit of methyl-coenzyme-M reductase involved in the final step of methanogenesis. BLASTn analysis applying stringent settings resulted in assignment of 16S-rDNA metagenome sequence reads to 62 16S-rDNA amplicon sequences thus enabling frequency of abundance estimations for 16S-rDNA clone library sequences. Ribosomal Database Project (RDP) Classifier processing of metagenome 16S-rDNA reads revealed abundance of the phyla Firmicutes, Bacteroidetes and Euryarchaeota and the orders Clostridiales, Bacteroidales and Methanomicrobiales. Moreover, a large fraction of 16S-rDNA metagenome reads could not be assigned to lower taxonomic ranks, demonstrating that numerous microorganisms in the analysed fermentation sample of the biogas plant are still unclassified or unknown. Mon, 01 Jun 2009 04:00:00 GMT http://www.ncbi.nlm.nih.gov/pubmed/19480946 2009-06-01T04:00:00Z http://www.ncbi.nlm.nih.gov/pubmed/19507517 The intestinal microbes are taxonomically complex and constitute an ecologically dynamic community (microbiota) that has long been believed to possess a strong impact on human physiology. Furthermore, they are heavily involved in the maturation and proliferation of human intestinal cells, leading to maintain their homeostasis, and can be causative of various diseases such as inflammatory bowel disease and obesity. A culture-independent approach 'metagenomics' now makes it possible to comprehensively explore the genetic nature of intestinal microbiome (collective genomes of microbes), providing the mechanistic basis for the functional roles of intestinal microbiome. The International Human Microbiome Project was recently launched to further promote this newly developing field, which will provide new strategies for the maintenance of human health. Wed, 10 Jun 2009 04:00:00 GMT http://www.ncbi.nlm.nih.gov/pubmed/19507517 2009-06-10T04:00:00Z http://www.ncbi.nlm.nih.gov/pubmed/19264858 BACKGROUND: The Human Microbiome Project has ushered in a new era for human metagenomics and high-throughput next-generation sequencing strategies. CONTENT: This review describes evolving strategies in metagenomics, with a special emphasis on the core technology of DNA pyrosequencing. The challenges of microbial identification in the context of microbial populations are discussed. The development of next-generation pyrosequencing strategies and the technical hurdles confronting these methodologies are addressed. Bioinformatics-related topics include taxonomic systems, sequence databases, sequence-alignment tools, and classifiers. DNA sequencing based on 16S rRNA genes or entire genomes is summarized with respect to potential pyrosequencing applications. SUMMARY: Both the approach of 16S rDNA amplicon sequencing and the whole-genome sequencing approach may be useful for human metagenomics, and numerous bioinformatics tools are being deployed to tackle such vast amounts of microbiological sequence diversity. Metagenomics, or genetic studies of microbial communities, may ultimately contribute to a more comprehensive understanding of human health, disease susceptibilities, and the pathophysiology of infectious and immune-mediated diseases. Mon, 27 Apr 2009 04:00:00 GMT http://www.ncbi.nlm.nih.gov/pubmed/19264858 2009-04-27T04:00:00Z http://www.ncbi.nlm.nih.gov/pubmed/19340927 Wed, 01 Apr 2009 04:00:00 GMT http://www.ncbi.nlm.nih.gov/pubmed/19340927 2009-04-01T04:00:00Z