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Structure, Function and Diversity of the Healthy Human Microbiome

The Human Microbiome Project Consortium

Nature

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      Abstract

      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 analyzed the largest cohort and set of distinct, clinically relevant body habitats to date. 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.

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      Most cited references 35

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      QIIME allows analysis of high-throughput community sequencing data.

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        Is Open Access

        Fast and accurate long-read alignment with Burrows–Wheeler transform

        Motivation: Many programs for aligning short sequencing reads to a reference genome have been developed in the last 2 years. Most of them are very efficient for short reads but inefficient or not applicable for reads >200 bp because the algorithms are heavily and specifically tuned for short queries with low sequencing error rate. However, some sequencing platforms already produce longer reads and others are expected to become available soon. For longer reads, hashing-based software such as BLAT and SSAHA2 remain the only choices. Nonetheless, these methods are substantially slower than short-read aligners in terms of aligned bases per unit time. Results: We designed and implemented a new algorithm, Burrows-Wheeler Aligner's Smith-Waterman Alignment (BWA-SW), to align long sequences up to 1 Mb against a large sequence database (e.g. the human genome) with a few gigabytes of memory. The algorithm is as accurate as SSAHA2, more accurate than BLAT, and is several to tens of times faster than both. Availability: http://bio-bwa.sourceforge.net Contact: rd@sanger.ac.uk
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          A human gut microbial gene catalogue established by metagenomic sequencing.

          To understand the impact of gut microbes on human health and well-being it is crucial to assess their genetic potential. Here we describe the Illumina-based metagenomic sequencing, assembly and characterization of 3.3 million non-redundant microbial genes, derived from 576.7 gigabases of sequence, from faecal samples of 124 European individuals. The gene set, approximately 150 times larger than the human gene complement, contains an overwhelming majority of the prevalent (more frequent) microbial genes of the cohort and probably includes a large proportion of the prevalent human intestinal microbial genes. The genes are largely shared among individuals of the cohort. Over 99% of the genes are bacterial, indicating that the entire cohort harbours between 1,000 and 1,150 prevalent bacterial species and each individual at least 160 such species, which are also largely shared. We define and describe the minimal gut metagenome and the minimal gut bacterial genome in terms of functions present in all individuals and most bacteria, respectively.
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            Author and article information

            Author notes
            Correspondence and requests for materials should be addressed to chuttenh@ 123456hsph.harvard.edu
            Journal
            0410462
            6011
            Nature
            Nature
            Nature
            0028-0836
            1476-4687
            17 May 2012
            13 June 2012
            05 February 2013
            : 486
            : 7402
            : 207-214
            22699609
            3564958
            10.1038/nature11234
            NIHMS378076

            Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms

            Funding
            Funded by: National Human Genome Research Institute : NHGRI
            Award ID: N01HG62088 || HG
            Funded by: National Institute of Allergy and Infectious Diseases Extramural Activities : NIAID
            Award ID: N01AI30071 || AI
            Funded by: National Institute of Diabetes and Digestive and Kidney Diseases : NIDDK
            Award ID: UH3 DK083993 || DK
            Funded by: National Institute of Allergy and Infectious Diseases Extramural Activities : NIAID
            Award ID: UH3 AI083263 || AI
            Funded by: National Institute of Diabetes and Digestive and Kidney Diseases : NIDDK
            Award ID: UH2 DK083990 || DK
            Funded by: National Institute of Arthritis and Musculoskeletal and Skin Diseases : NIAMS
            Award ID: UH2 AR057504 || AR
            Funded by: National Institute of Allergy and Infectious Diseases Extramural Activities : NIAID
            Award ID: UH2 AI083263 || AI
            Funded by: National Human Genome Research Institute : NHGRI
            Award ID: U54 HG004973 || HG
            Funded by: National Human Genome Research Institute : NHGRI
            Award ID: U54 HG004969 || HG
            Funded by: National Human Genome Research Institute : NHGRI
            Award ID: U54 HG004968 || HG
            Funded by: National Human Genome Research Institute : NHGRI
            Award ID: U54 HG003273 || HG
            Funded by: National Human Genome Research Institute : NHGRI
            Award ID: U54 HG003079 || HG
            Funded by: National Human Genome Research Institute : NHGRI
            Award ID: U54 HG003067 || HG
            Funded by: National Institute of Allergy and Infectious Diseases Extramural Activities : NIAID
            Award ID: U54 AI084844 || AI
            Funded by: National Institute of Allergy and Infectious Diseases Extramural Activities : NIAID
            Award ID: U54 AI084844 || AI
            Funded by: National Human Genome Research Institute : NHGRI
            Award ID: U01 HG004866 || HG
            Funded by: National Institute of Dental and Craniofacial Research : NIDCR
            Award ID: U01 DE016937 || DE
            Funded by: National Institute of Dental and Craniofacial Research : NIDCR
            Award ID: RC1 DE020298 || DE
            Funded by: National Institute of Dental and Craniofacial Research : NIDCR
            Award ID: RC1 DE020298 || DE
            Funded by: National Cancer Institute : NCI
            Award ID: R21 CA139193 || CA
            Funded by: National Human Genome Research Institute : NHGRI
            Award ID: R01 HG005975 || HG
            Funded by: National Human Genome Research Institute : NHGRI
            Award ID: R01 HG005969 || HG
            Funded by: National Human Genome Research Institute : NHGRI
            Award ID: R01 HG005172 || HG
            Funded by: National Human Genome Research Institute : NHGRI
            Award ID: R01 HG005171 || HG
            Funded by: National Human Genome Research Institute : NHGRI
            Award ID: R01 HG004908 || HG
            Funded by: National Human Genome Research Institute : NHGRI
            Award ID: R01 HG004906 || HG
            Funded by: National Human Genome Research Institute : NHGRI
            Award ID: R01 HG004900 || HG
            Funded by: National Human Genome Research Institute : NHGRI
            Award ID: R01 HG004885 || HG
            Funded by: National Human Genome Research Institute : NHGRI
            Award ID: R01 HG004877 || HG
            Funded by: National Human Genome Research Institute : NHGRI
            Award ID: R01 HG004872 || HG
            Funded by: National Human Genome Research Institute : NHGRI
            Award ID: R01 HG004857 || HG
            Funded by: National Human Genome Research Institute : NHGRI
            Award ID: R01 HG004856 || HG
            Funded by: National Human Genome Research Institute : NHGRI
            Award ID: R01 HG004853 || HG
            Funded by: National Institute of Dental and Craniofacial Research : NIDCR
            Award ID: R01 DE021574 || DE
            Funded by: National Institute of Dental and Craniofacial Research : NIDCR
            Award ID: R01 DE021574 || DE
            Funded by: National Institute of Dental and Craniofacial Research : NIDCR
            Award ID: P30 DE020751 || DE
            Funded by: Office of the Director : NIH
            Award ID: DP2 OD001500 || OD
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