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Lien entre glucides et cancer du colon

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Lien entre glucides et cancer du colon

Messagepar audiomaniac le 26/07 22h10

Gut Microbial Metabolism Drives Transformation of Msh2-Deficient Colon Epithelial Cells
Cell Volume 158, Issue 2, p288–299, 17 July 2014 Antoaneta Belcheva

Highlights

•Gut microbiota induce colon cancer in genetically sensitized MSH2-deficient mice
•Reduced dietary carbohydrates decreased polyp frequency in APCMin/+MSH2−/− mice
•The carbohydrate metabolite butyrate induces colon cancer in APCMin/+MSH2−/− mice
•MSH2 regulates β-catenin activity and/or transit-amplifying cell differentiation

The etiology of colorectal cancer (CRC) has been linked to deficiencies in mismatch repair and adenomatous polyposis coli (APC) proteins, diet, inflammatory processes, and gut microbiota. However, the mechanism through which the microbiota synergizes with these etiologic factors to promote CRC is not clear. We report that altering the microbiota composition reduces CRC in APCMin/+MSH2−/− mice, and that a diet reduced in carbohydrates phenocopies this effect. Gut microbes did not induce CRC in these mice through an inflammatory response or the production of DNA mutagens but rather by providing carbohydrate-derived metabolites such as butyrate that fuel hyperproliferation of MSH2−/− colon epithelial cells. Further, we provide evidence that the mismatch repair pathway has a role in regulating β-catenin activity and modulating the differentiation of transit-amplifying cells in the colon. These data thereby provide an explanation for the interaction between microbiota, diet, and mismatch repair deficiency in CRC induction.

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