title: 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, 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 APCmin/+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. Our study demonstrated that alteration of the microbial community induced by DCA promoted intestinal carcinogenesis.
authors.affiliation: 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.
authors.forename: Hailong
authors.initials: H
authors.lastname: Cao
authors.affiliation: Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, Tianjin, People's Republic of China.|Department of Gastroenterology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, People's Republic of China.
authors.forename: Mengque
authors.initials: M
authors.lastname: Xu
authors.affiliation: Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, Tianjin, People's Republic of China.
authors.forename: Wenxiao
authors.initials: W
authors.lastname: Dong
authors.affiliation: Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, Tianjin, People's Republic of China.
authors.forename: Baoru
authors.initials: B
authors.lastname: Deng
authors.affiliation: Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, Tianjin, People's Republic of China.
authors.forename: Sinan
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Pathology, General Hospital, Tianjin Medical University, Tianjin, People's Republic of China.
authors.forename: Yujie
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, Tianjin, People's Republic of China.
authors.forename: Shan
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, Tianjin, People's Republic of China.
authors.forename: Shenhui
authors.initials: S
authors.lastname: Luo
authors.affiliation: Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, Tianjin, People's Republic of China.
authors.forename: Weiqiang
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology and Hepatology, Tianjin Haibin People's Hospital, Tianjin, People's Republic of China.
authors.forename: Yanrong
authors.initials: Y
authors.lastname: Qi
authors.affiliation: Department of Gastroenterology and Hepatology, Tianjin Haibin People's Hospital, Tianjin, People's Republic of China.
authors.forename: Jianxin
authors.initials: J
authors.lastname: Gao
authors.affiliation: Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, Tianjin, People's Republic of China.
authors.forename: Xiaocang
authors.initials: X
authors.lastname: Cao
authors.affiliation: 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.
authors.forename: Fang
authors.initials: F
authors.lastname: Yan
authors.affiliation: Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, Tianjin, People's Republic of China.
authors.forename: Bangmao
authors.identifier: 0000-0003-2796-1584
authors.initials: B
authors.lastname: Wang
mesh_terms: D000818:Animals; D001647:Bile Acids and Salts / Q000009:adverse effects*; D063646:Carcinogenesis / Q000139:chemically induced* / Q000473:pathology; D003840:Deoxycholic Acid / Q000009:adverse effects; D064806:Dysbiosis / Q000139:chemically induced* / Q000382:microbiology / Q000473:pathology; D005243:Feces / Q000382:microbiology; D007249:Inflammation / Q000382:microbiology / Q000473:pathology; D007422:Intestines / Q000382:microbiology / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D064307:Microbiota / Q000187:drug effects; D060449:Wnt Signaling Pathway / Q000187:drug effects; D051176:beta Catenin / Q000378:metabolism
chemical_list: D001647:Bile Acids and Salts; D051176:beta Catenin; D003840:Deoxycholic Acid
keywords: Apcmin/+ mice; deoxycholic acid; intestinal carcinogenesis; intestinal microbiota; tumor-associated macrophages