Importance of disrupted intestinal barrier in inflammatory bowel diseases

Authors

  • Sa'ad Y. Salim PhD,

    1. Department of Clinical and Experimental Medicine, Division of Surgery and Clinical Oncology, Faculty of Health Sciences, Linköping University, Linköping, Sweden
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  • Johan D. Söderholm MD, PhD

    Corresponding author
    1. Department of Clinical and Experimental Medicine, Division of Surgery and Clinical Oncology, Faculty of Health Sciences, Linköping University, Linköping, Sweden
    • Department of Clinical and Experimental Medicine, Division of Surgery, University Hospital, SE-581 85 Linköping, Sweden
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  • J.D. Söderholm's research on intestinal barrier function in inflammatory bowel disease was supported by the Swedish Research Council – Medicine, and the Broad Medical Research Program of Eli and Edythe L Broad Foundation.

Abstract

The current paradigm of inflammatory bowel diseases (IBD), both Crohn's disease (CD) and ulcerative colitis (UC), involves the interaction between environmental factors in the intestinal lumen and inappropriate host immune responses in genetically predisposed individuals. The intestinal mucosal barrier has evolved to maintain a delicate balance between absorbing essential nutrients while preventing the entry and responding to harmful contents. In IBD, disruptions of essential elements of the intestinal barrier lead to permeability defects. These barrier defects exacerbate the underlying immune system, subsequently resulting in tissue damage. The epithelial phenotype in active IBD is very similar in CD and UC. It is characterized by increased secretion of chloride and water, leading to diarrhea, increased permeability via both the transcellular and paracellular routes, and increased apoptosis of epithelial cells. The main cytokine that seems to drive these changes is tumor necrosis factor alpha in CD, whereas interleukin (IL)-13 may be more important in UC. Therapeutic restoration of the mucosal barrier would provide protection and prevent antigenic overload due to intestinal “leakiness.” Here we give an overview of the key players of the intestinal mucosal barrier and review the current literature from studies in humans and human systems on mechanisms underlying mucosal barrier dysfunction in IBD. (Inflamm Bowel Dis 2011;)

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