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Influence de la consommation alimentaire en sucre sur la sévérité de la colite chez l'animal et modulation du microbiote intestinal

Abstract : Inflammatory bowel diseases (IBD) are chronic diseases characterized by inflammation of the mucosa associated with gut microbiota dysbiosis and overreaction of the immune system. IBD prevalence is increasing in industrialized countries where the western dietary pattern is involved in many pathologies such as obesity, diabetes, and cancers. Nutrition appears to be an important environmental factor involved in IBD onset through poorly understood biological mechanisms. Here we focused on the early consequences of a diet enriched in sugar (sucrose) because it represents up to 25% of total energy intake within industrialized countries, while the WHO recommends reducing it to less than 5%. We studied the effects of high sucrose diet on intestinal homeostasis and experimental colitis in mice. In healthy subjects, this diet caused endoscopic lesions, thus predisposing to colitis. The worsening of colitis was preceded by gut microbiota dysbiosis with complete depletion of bacteria belonging to Barnesiella and transcriptional reprogramming of colonic genes, associated with IBD according to functional annotations. In cellulo, a low dose of fructose induced cell junctions’ alterations, while a high dose of glucose was needed to induce similar damage. After colitogenic treatment, the high sugar diet worsens the severity of clinical and endoscopic signs by disrupting the organization of cell-cell junctions and the autophagy process in intestinal cells. Such in-vivo effects on mice microbiome and transcriptome were partially reversible upon mice return to control diet. Finally, sugar overconsumption induces a "pre-IBD" state characterized by an overall downregulation of the colonic transcriptome in mice together with immunodepression, significant alterations in cellular architecture, and gut microbiota dysbiosis. Our findings support international recommendations about reducing sugar consumption to reduce the risk of developing or worsening intestinal inflammation.
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Submitted on : Wednesday, June 30, 2021 - 12:19:14 PM
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Djésia Arnone. Influence de la consommation alimentaire en sucre sur la sévérité de la colite chez l'animal et modulation du microbiote intestinal. Biochimie, Biologie Moléculaire. Université de Lorraine, 2020. Français. ⟨NNT : 2020LORR0247⟩. ⟨tel-03274646⟩



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