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Intestinal barrier dysfunction in inflammatory bowel diseases

McGuckin, Michael A. PhD1,*; Eri, Rajaraman PhD1,2; Simms, Lisa A. BSc3,4,5; Florin, Timothy H.J. MD2; Radford‐Smith, Graham DPhil3,4,5

Inflammatory Bowel Diseases:
doi: 10.1002/ibd.20539
Basic Science Reviews
Abstract

The etiology of human inflammatory bowel diseases (IBDs) is believed to involve inappropriate host responses to the complex commensal microbial flora in the gut, although an altered commensal flora is not completely excluded. A multifunctional cellular and secreted barrier separates the microbial flora from host tissues. Altered function of this barrier remains a major largely unexplored pathway to IBD. Although there is evidence of barrier dysfunction in IBD, it remains unclear whether this is a primary contributor to disease or a consequence of mucosal inflammation. Recent evidence from animal models demonstrating that genetic defects restricted to the epithelium can initiate intestinal inflammation in the presence of normal underlying immunity has refocused attention on epithelial dysfunction in IBD. We review the components of the secreted and cellular barrier, their regulation, including interactions with underlying innate and adaptive immunity, evidence from animal models of the barrier's role in preventing intestinal inflammation, and evidence of barrier dysfunction in both Crohn's disease and ulcerative colitis.

Author Information

1 Mucin Research Team, Mucosal Diseases Program, Mater Medical Research Institute, and the University of Queensland, Aubigny Place, Mater Health Services, South Brisbane, Queensland, Australia

2 IBD Research Team, Mucosal Diseases Program, Mater Medical Research Institute, and the University of Queensland, Aubigny Place, Mater Health Services, South Brisbane, Queensland, Australia

3 Inflammatory Bowel Disease Laboratory, Royal Brisbane and Women's Research Foundation, Brisbane, Australia

4 Queensland Institute of Medical Research, Brisbane, Australia

5 Department of Gastroenterology, Royal Brisbane and Women's Hospital, Brisbane, Australia

* University of Queensland, Aubigny Place, Mater Health Services, South Brisbane, Qld 4101, Australia

Email: mmcguckin@mmri.mater.org.au

Received 13 May 2008; Accepted 15 May 2008

Published online 11 July 2008 in Wiley InterScience (www.interscience.wiley.com).

© Crohn's & Colitis Foundation of America, Inc.

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