Secondary bile acid‐induced dysbiosis promotes intestinal carcinogenesis. Issue 11 (1st March 2017)

• Record Type: Journal Article
• Authors: Cao, Hailong; Xu, Mengque; Dong, Wenxiao; Deng, Baoru; Wang, Sinan; Zhang, Yujie; Wang, Shan; Luo, Shenhui; Wang, Weiqiang; Qi, Yanrong; Gao, Jianxin; Cao, Xiaocang; Yan, Fang; Wang, Bangmao
• Is Part Of: International journal of cancer. Volume 140:Issue 11(2017:Jun. 01)
• Page Start: 2545
• Page End: 2556
• Publication Date: 2017-03-01
• Subjects: deoxycholic acid -- intestinal microbiota -- Apcmin/+ mice -- intestinal carcinogenesis -- tumor‐associated macrophages; Cancer -- Periodicals; Cancer -- Prevention -- Periodicals; 616.994
• DOI: 10.1002/ijc.30643
• Languages: English
• ISSNs: 0020-7136

Abstract

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, correlates with intestinal carcinogenesis. However, evidence relating bile acids, intestinal microbiota and tumorigenesis are limited. In our 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 APC min/+ 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 Apc min/+ 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. Our study demonstrated that alteration of the microbial community induced by DCA promoted intestinal carcinogenesis. Abstract : What's new? Microbial imbalance in the intestines, or gut dysbiosis, is a suspected contributor to intestinal tumor development. Likewise, deoxycholic acid (DCA), a secondary bile acid elevated by a high‐fat diet, is thought to be pro‐carcinogenic. Our study shows that the two factors, working together, pave the way to intestinal tumorigenesis. In mutationally predisposed mice, DCA‐induced dysbiosis disrupted intestinal barrier function, promoted recruitment of tumor‐associated macrophages and accelerated intestinal carcinogenesis via activation of Wnt/β‐catenin signaling. DCA‐induced tumor growth and inflammation were reduced in mice depleted of gut microbiota by antibiotic supplementation, further implicating DCA and gut dysbiosis in intestinal carcinogenesis.