Review Article

Mechanisms of Disease: pathogenesis of Crohn's disease and ulcerative colitis

  • Nature Clinical Practice Gastroenterology & Hepatology volume 3, pages 390407 (2006)
  • doi:10.1038/ncpgasthep0528
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Abstract

Crohn's disease and ulcerative colitis are idiopathic, chronic, relapsing, inflammatory conditions that are immunologically mediated. Although their exact etiologies remain uncertain, results from research in animal models, human genetics, basic science and clinical trials have provided important new insights into the pathogenesis of chronic, immune-mediated, intestinal inflammation. These studies indicate that Crohn's disease and ulcerative colitis are heterogeneous diseases characterized by various genetic abnormalities that lead to overly aggressive T-cell responses to a subset of commensal enteric bacteria. The onset and reactivation of disease are triggered by environmental factors that transiently break the mucosal barrier, stimulate immune responses or alter the balance between beneficial and pathogenic enteric bacteria. Different genetic abnormalities can lead to similar disease phenotypes; these genetic changes can be broadly characterized as causing defects in mucosal barrier function, immunoregulation or bacterial clearance. These new insights will help develop better diagnostic approaches that identify clinically important subsets of patients for whom the natural history of disease and response to treatment are predictable.

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Acknowledgements

Original research was supported by NIH RO1 grants DK40249 and DK 53347. The author thanks S May for her expert secretarial assistance.

Author information

Affiliations

  1. RB Sartor is the Margaret W and Lorimer W Midgette Distinguished Professor in the Departments of Medicine, Microbiology and Immunology at the University of North Carolina, Chapel Hill, NC, USA, where he is the Director of the Multidisciplinary Inflammatory Bowel Disease Center, Co-Director of the Center for Gastrointestinal Biology and Disease, and Associate Chief for Research of the University of North Carolina Division of Gastroenterology and Hepatology.

    • R Balfour Sartor

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Competing interests

The author has received research grant support from VSL Pharmaceuticals, Salix Pharmaceuticals, and Procter & Gamble. He is a consultant for Danone/Yakult companies and has given talks sponsored by Salix and Berlex companies.