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Advances in inflammatory bowel disease pathogenesis: linking host genetics and the microbiome
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  1. Dan Knights1,2,3,
  2. Kara G Lassen1,2,
  3. Ramnik J Xavier1,2,4
  1. 1Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
  2. 2Center for Computational and Integrative Biology, Massachusetts General Hospital, Boston, Massachusetts, USA
  3. 3Department of Computer Science and Engineering, University of Minnesota, Minneapolis, Minnesota, USA
  4. 4Gastrointestinal Unit, Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
  1. Correspondence to Dr Ramnik J Xavier, Center for Computational and Integrative Biology, Massachusetts General Hospital, 185 Cambridge Street, Simches 7222, Boston, MA 02114, USA; xavier{at}molbio.mgh.harvard.edu

Abstract

Studies of the genetics underlying inflammatory bowel diseases have increased our understanding of the pathways involved in both ulcerative colitis and Crohn's disease and focused attention on the role of the microbiome in these diseases. Full understanding of pathogenesis will require a comprehensive grasp of the delicate homeostasis between gut bacteria and the human host. In this review, we present current evidence of microbiome–gene interactions in the context of other known risk factors and mechanisms, and describe the next steps necessary to pair genetic variant and microbiome sequencing data from patient cohorts. We discuss the concept of dysbiosis, proposing that the functional composition of the gut microbiome may provide a more consistent definition of dysbiosis and may more readily provide evidence of genome–microbiome interactions in future exploratory studies.

  • INFLAMMATORY BOWEL DISEASE
  • GENETICS
  • INTESTINAL BACTERIA
  • CROHN'S DISEASE
  • ULCERATIVE COLITIS

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