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
Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, Tianjin, People's Republic of China.
Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN.
Int J Cancer. 2017 Jun 1;140(11):2545-2556. doi: 10.1002/ijc.30643. Epub 2017 Mar 1.
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 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 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.
肠道微生物群在维持肠道内稳态中发挥着重要作用。肠道微生物群失调与肠道肿瘤发生有关。脱氧胆酸（DCA）是一种因西方饮食而增加的次级胆汁酸，与肠道癌变相关。然而，有关胆汁酸、肠道微生物群和肿瘤发生之间关系的证据有限。在我们的研究中，我们调查了DCA对肠道微生物群失调诱导的影响及其在肠道癌变中的作用。DCA处理的Apc小鼠肠道微生物群组成发生改变，同时伴有肠道屏障受损、肠道低度炎症和肿瘤进展。将DCA处理小鼠的粪便微生物群移植到另一组Apc小鼠中，增加了肿瘤的多发性，诱导了炎症，并募集了M2表型肿瘤相关巨噬细胞。重要的是，粪便微生物群移植激活了肿瘤相关的Wnt/β-连环蛋白信号通路。此外，用抗生素鸡尾酒耗尽微生物群足以阻断DCA诱导的肠道癌变，进一步表明微生物群失调在肿瘤发展中的作用。我们的研究表明，DCA诱导的微生物群落改变促进了肠道癌变。
