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Multi-omics of the gut microbial ecosystem in inflammatory bowel diseases.


ABSTRACT: Inflammatory bowel diseases, which include Crohn's disease and ulcerative colitis, affect several million individuals worldwide. Crohn's disease and ulcerative colitis are complex diseases that are heterogeneous at the clinical, immunological, molecular, genetic, and microbial levels. Individual contributing factors have been the focus of extensive research. As part of the Integrative Human Microbiome Project (HMP2 or iHMP), we followed 132 subjects for one year each to generate integrated longitudinal molecular profiles of host and microbial activity during disease (up to 24 time points each; in total 2,965 stool, biopsy, and blood specimens). Here we present the results, which provide a comprehensive view of functional dysbiosis in the gut microbiome during inflammatory bowel disease activity. We demonstrate a characteristic increase in facultative anaerobes at the expense of obligate anaerobes, as well as molecular disruptions in microbial transcription (for example, among clostridia), metabolite pools (acylcarnitines, bile acids, and short-chain fatty acids), and levels of antibodies in host serum. Periods of disease activity were also marked by increases in temporal variability, with characteristic taxonomic, functional, and biochemical shifts. Finally, integrative analysis identified microbial, biochemical, and host factors central to this dysregulation. The study's infrastructure resources, results, and data, which are available through the Inflammatory Bowel Disease Multi'omics Database ( http://ibdmdb.org ), provide the most comprehensive description to date of host and microbial activities in inflammatory bowel diseases.

SUBMITTER: Lloyd-Price J 

PROVIDER: S-EPMC6650278 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Multi-omics of the gut microbial ecosystem in inflammatory bowel diseases.

Lloyd-Price Jason J   Arze Cesar C   Ananthakrishnan Ashwin N AN   Schirmer Melanie M   Avila-Pacheco Julian J   Poon Tiffany W TW   Andrews Elizabeth E   Ajami Nadim J NJ   Bonham Kevin S KS   Brislawn Colin J CJ   Casero David D   Courtney Holly H   Gonzalez Antonio A   Graeber Thomas G TG   Hall A Brantley AB   Lake Kathleen K   Landers Carol J CJ   Mallick Himel H   Plichta Damian R DR   Prasad Mahadev M   Rahnavard Gholamali G   Sauk Jenny J   Shungin Dmitry D   Vázquez-Baeza Yoshiki Y   White Richard A RA   Braun Jonathan J   Denson Lee A LA   Jansson Janet K JK   Knight Rob R   Kugathasan Subra S   McGovern Dermot P B DPB   Petrosino Joseph F JF   Stappenbeck Thaddeus S TS   Winter Harland S HS   Clish Clary B CB   Franzosa Eric A EA   Vlamakis Hera H   Xavier Ramnik J RJ   Huttenhower Curtis C  

Nature 20190529 7758


Inflammatory bowel diseases, which include Crohn's disease and ulcerative colitis, affect several million individuals worldwide. Crohn's disease and ulcerative colitis are complex diseases that are heterogeneous at the clinical, immunological, molecular, genetic, and microbial levels. Individual contributing factors have been the focus of extensive research. As part of the Integrative Human Microbiome Project (HMP2 or iHMP), we followed 132 subjects for one year each to generate integrated longi  ...[more]

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