2. Academic Validation
  3. Cholecystectomy-related gut microbiota dysbiosis exacerbates colorectal tumorigenesis

Cholecystectomy-related gut microbiota dysbiosis exacerbates colorectal tumorigenesis

  • Nat Commun. 2025 Aug 16;16(1):7638. doi: 10.1038/s41467-025-62956-8.
Bo Tang # 1,  Shengpeng Li # 1,  Xin Li # 1,  Jialin He 1,  An Zhou 1,  Lingyi Wu 1,  Xu Xiao 1,  Sumin Wang 1,  Hongfei Jiang 1,  Jincheng Jian 1,  Zhanjie Hou 1,  Yusong Ge 1,  Yuanyuan Lei 1,  Jianchun Zhou 1,  Dianji Tu 1 2,  Cheng Lu 3,  Min Yang 4,  Shiming Yang 5 6 7
Affiliations

Affiliations

  • 1 Department of Gastroenterology, Xinqiao Hospital, Army Medical University, Chongqing, China.
  • 2 Laboratory Medicine Center, Xinqiao Hospital, Army Medical University, Chongqing, China.
  • 3 Department of Gastroenterology, Xinqiao Hospital, Army Medical University, Chongqing, China. lucheng1108@tmmu.edu.cn.
  • 4 Department of Gastroenterology, Xinqiao Hospital, Army Medical University, Chongqing, China. Yangmin1990@tmmu.edu.cn.
  • 5 Department of Gastroenterology, Xinqiao Hospital, Army Medical University, Chongqing, China. Yangshiming@tmmu.edu.cn.
  • 6 Chongqing Institute for Brain and Intelligence, Guangyang Bay Laboratory, Chongqing, China. Yangshiming@tmmu.edu.cn.
  • 7 Chongqing Municipality Clinical Research Center for Gastroenterology, Chongqing, China. Yangshiming@tmmu.edu.cn.
  • # Contributed equally.
PMID: 40819131 DOI: 10.1038/s41467-025-62956-8
Abstract

Cholecystectomy represents the most prevalent biliary surgical procedure for gallbladder abnormalities. Growing evidence suggests that cholecystectomy is associated with an elevated risk of colorectal Cancer. However, the underlying mechanism remains elusive. Here we show that cholecystectomy exacerbates colorectal tumorigenesis in both AOM/DSS and APCmin/+ mice models. Metagenomic Sequencing and targeted metabolomics show that cholecystectomy leads to a decrease of Bifidobacterium breve (B. breve) and an increase of Ruminococcus gnavus (R. gnavus), along with increased levels of glycoursodeoxycholic acid (GUDCA) in human and tauroursodeoxycholic acid (TUDCA) in mice. Fecal microbiota transplantation, single Bacterial colonization and bile acid supplementation demonstrate that cholecystectomy-related gut microbiota perturbations promote the production of TUDCA and facilitate colorectal tumorigenesis. RNA-sequencing and co-immunoprecipitation reveal that the compromised bile acid metabolism inhibits farnesoid X receptor (FXR) signaling, disrupts the FXR/β-catenin interaction, and ultimately exacerbates colorectal tumorigenesis. Significantly, FXR Agonist obeticholic acid (OCA) averts cholecystectomy-related colorectal tumorigenesis. The gut microbiota holds a crucial position in cholecystectomy-induced colorectal tumorigenesis, and modulation of the gut microbiota-bile acid-FXR axis represents a promising preventive strategy.

Figures
Products
Inhibitors & Agonists
Other Products