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Deoxynivalenol (DON), a mycotoxin produced by Fusarium species, is a frequent contaminant of grains and cereal products worldwide. DON causes many toxic effects on growth, immune response, reproduction, development… At the intestinal level, DON has been demonstrated to affect key immune functions which could lead to the induction and/or persistence of intestinal diseases. The potential link between DON exposure and human Inflammatory Bowel Diseases (IBD) is the global aim of this proposal. Indeed, the different actors participating to the pathophysiological process leading to IBD development are still not well understood. We hypothesize that an improper detoxification of DON, implicating gut microflora and/or endogenous enzymes, would lead to an increased susceptibility to DON toxicity in IBD patients. The objectives of this proposal are to compare, in healthy and IBD suffering individuals: 1) the cartography of DON absorption, distribution, metabolism and excretion; 2) the detoxification of DON by the gut and the consequences in term of immune homeostasis of DON exposure ; 3) the effects of DON on the gut microbiota composition and the reciprocal effect of the gut microbiota on DON metabolism studied in vitro. The study of consequences of oral subchronic exposure of DON in humanized gnotobiotic mice colonized with a healthy or an IBD patient microbiota is our fourth objective. Our proposal is interdisciplinary bringing together gastroenterologists and researchers on nutrition, risk assessment, pathophysiology and microbiology.
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