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The Microbiome in Inflammatory Bowel Disease: Current Status and the Future Ahead

  • Aleksandar D. Kostic
    Affiliations
    Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts
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  • Ramnik J. Xavier
    Correspondence
    Reprint requests Address requests for reprints to: Ramnik J. Xavier, MD, PhD, Center for Computational and Integrative Biology, Richard B. Simches Research Center, Massachusetts General Hospital, 185 Cambridge Street, Boston, Massachusetts 02114. fax: (617) 724 6832.
    Affiliations
    Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts

    Gastrointestinal Unit, Center for the Study of Inflammatory Bowel Disease, and Center for Computational and Integrative Biology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
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  • Dirk Gevers
    Affiliations
    Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts
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Published:February 21, 2014DOI:https://doi.org/10.1053/j.gastro.2014.02.009
      Studies of the roles of microbial communities in the development of inflammatory bowel disease (IBD) have reached an important milestone. A decade of genome-wide association studies and other genetic analyses have linked IBD with loci that implicate an aberrant immune response to the intestinal microbiota. More recently, profiling studies of the intestinal microbiome have associated the pathogenesis of IBD with characteristic shifts in the composition of the intestinal microbiota, reinforcing the view that IBD results from altered interactions between intestinal microbes and the mucosal immune system. Enhanced technologies can increase our understanding of the interactions between the host and its resident microbiota and their respective roles in IBD from both a large-scale pathway view and at the metabolic level. We review important microbiome studies of patients with IBD and describe what we have learned about the mechanisms of intestinal microbiota dysfunction. We describe the recent progress in microbiome research from exploratory 16S-based studies, reporting associations of specific organisms with a disease, to more recent studies that have taken a more nuanced view, addressing the function of the microbiota by metagenomic and metabolomic methods. Finally, we propose study designs and methodologies for future investigations of the microbiome in patients with inflammatory gut and autoimmune diseases in general.

      Keywords

      Abbreviations used in this paper:

      CD (Crohn's disease), FMT (fecal microbiota transplantation), IBD (inflammatory bowel disease), iCD (ileal Crohn's disease), SCFA (short-chain fatty acid), T2DM (type 2 diabetes mellitus), UC (ulcerative colitis)
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