Determinants of colonic barrier function in inflammatory bowel disease and potential therapeutics.

Intestinal barrier dysfunction is a main feature of the inflammatory bowel diseases (IBD), Crohn's disease and ulcerative colitis. Leak flux diarrhoea and a facilitated uptake of noxious antigens are the two consequences resulting from an impaired epithelial barrier. Barrier perturbations in IBD comprise alterations in epithelial tight junctions (TJ), i.e. a reduced number of horizontal TJ strands and an altered TJ protein expression and subcellular distribution. Moreover, increased incidence of apoptotic events as well as erosions and ulcerations can add to that leakiness. These barrier defects are attributed to enhanced activity of pro-inflammatory cytokines like TNFα, INFγ, IL-1β and IL-13, which are highly expressed in the chronically inflamed intestine. Although the aetiology of IBD is far from being clear, chronic inflammation is believed to result from an inadequate immune response as a consequence of genetic predisposition as well as changes in, and altered responses to, the intestinal microbiota. On the other hand, an insufficient mucosal response to bacterial stimuli results in an insufficient immune response towards intestinal pathogens. However, detailed characterization of barrier defects offers the opportunity to consider and test therapeutic interventions. Beside cytokine antagonists, different plant compounds and probiotics have been shown to stabilize the barrier function by affecting TJ protein expression and distribution.