Παρασκευή, 10 Φεβρουαρίου 2017

Secondary bile acid-induced dysbiosis promotes intestinal carcinogenesis

Abstract

The gut microbiota plays an important role in maintaining intestinal homeostasis. Dysbiosis is associated with intestinal tumorigenesis. Deoxycholic acid (DCA), a secondary bile acid increased by a western diet, is associated with intestinal carcinogenesis. However, evidence relating bile acids, intestinal microbiota and tumorigenesis is limited. In this study, we investigated the effect of DCA on induction of intestinal dysbiosis and its roles in intestinal carcinogenesis. Alteration of the composition of the intestinal microbiota was induced in DCA-treated mice, which was accompanied by impaired intestinal barrier, gut low grade inflammation and tumor progression. The transfer of fecal microbiota from DCA-treated mice to another group of Apcmin/+ mice increased tumor multiplicity, induced inflammation and recruited M2 phenotype tumor-associated macrophages. Importantly, the fecal microbiota transplantation activated the tumor associated Wnt/β-catenin signaling pathway. Moreover, microbiota depletion by a cocktail of antibiotics was sufficient to block DCA-induced intestinal carcinogenesis, further suggesting the role of dysbiosis in tumor development. This study demonstrated that alteration of the microbial community induced by DCA promoted intestinal carcinogenesis. This article is protected by copyright. All rights reserved.



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