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Significance of increased human colonic permeability in response to corticotrophin-releasing hormone (CRH)

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Intestinal barrier impairment has been extensively described in various human pathologies, including gastrointestinal symptoms of non-digestive pathologies. However, whether barrier defects trigger or are a consequence of pathologies remains under debate. Barrier integrity lies on a complex and dynamic relationship between several components : (1) motility and peristaltism limit bacterial translocation and overgrowth, and the retrograde colonization of small intestine by colonic flora; (2) gut ecology exerts trophic effects (proliferation/differentiation) on epithelial cells, stimulates intestinal immune system maturation, and competes with potential pathogens; (3) the gut-associated lymphoid tissue (GALT) is built upon a close relationship between epithelium and diffuse immune cells, and specialised structures that may be referred as “lymphoid islets”; (4) the continuous epithelial lining of the gut allows nutrients to reach the interior milieu, and limits the passage of harmful compounds into the submucosal compartment. This epithelial barrier lies on four parameters: tight and adherens junctions which maintain epithelial cohesion, transcellular uptake, mucus and antimicrobial products.

The efficiency of the gut to maintain homeostasis requires a harmonious and dynamic interplay between all these actors, which should not been considered as a steady state. Indeed, gut motility, fast epithelial renewal, and harmful or harmless signals from both luminal and endogenous elements continuously flooding the barrier illustrate this dynamism, and thus the “fine tuning” needed to maintain a functional barrier. Therefore, it points out the difficulty for investigators to study the overall physiology of the intestinal barrier. In this context, the study of stress effects on the intestinal barrier well illustrates the challenge we have to face.

With respect to human GI pathologies, stressful life events are known to contribute to the development and perpetuation of inflammatory bowel diseases (IBD) as well as clinical course of irritable bowel syndrome (IBS). This appears not surprising since stress affects gut motility, mucus …

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