Gut Microbiome and Bile Acid Interactions: Mechanistic Implications for Cholangiocarcinoma Development, Immune Resistance, and Therapy
Document Type
Journal Article
Publication Date
3-1-2025
Journal
The American journal of pathology
Volume
195
Issue
3
DOI
10.1016/j.ajpath.2024.11.004
Abstract
Cholangiocarcinoma (CCA) is a rare but highly malignant carcinoma of bile duct epithelial cells with a poor prognosis. The major risk factors of CCA carcinogenesis and progression are cholestatic liver diseases. The key feature of primary sclerosing cholangitis and primary biliary cholangitis is chronic cholestasis. It indicates a slowdown of hepatocyte secretion of biliary lipids and metabolites into bile as well as a slowdown of enterohepatic circulation (bile acid recirculation) of bile acids with dysbiosis of the gut microbiome. This leads to enterohepatic recirculation and an increase of toxic secondary bile acids. Alterations of serum and liver bile acid compositions via the disturbed enterohepatic circulation of bile acids and the disturbance of the gut microbiome then activate a series of hepatic and cancer cell signaling pathways that promote CCA carcinogenesis and progression. This review focuses on the mechanistic roles of bile acids and the gut microbiome in the pathogenesis and progression of CCA. It also evaluates the therapeutic potential of targeting the gut microbiome and bile acid-mediated signaling pathways for the therapy and prophylaxis of CCA.
APA Citation
Wu, Nan; Bayatpour, Sareh; Hylemon, Phillip B.; Aseem, Sayed O.; Brindley, Paul J.; and Zhou, Huiping, "Gut Microbiome and Bile Acid Interactions: Mechanistic Implications for Cholangiocarcinoma Development, Immune Resistance, and Therapy" (2025). GW Authored Works. Paper 6930.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/6930
Department
Microbiology, Immunology, and Tropical Medicine