REVIEW article
Front. Oncol.
Sec. Gastrointestinal Cancers: Hepato Pancreatic Biliary Cancers
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1646897
Targeting the Gut-Liver Axis in Cholangiocarcinoma: Mechanisms, Therapeutic Advances, and Future Directions
Provisionally accepted
- 1Binzhou Medical University, Yantai, China
- 2Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
- 3The Chinese University of Hong Kong, Hong Kong, Hong Kong, SAR China
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Cholangiocarcinoma (CCA), a highly aggressive biliary tract malignancy, exhibits rising incidence rates and an extremely poor prognosis. Recent studies reveal that gut-liver axis dysregulation drives CCA progression through gut microbiota dysbiosis, bile acid (BA) metabolic disturbances, and immune microenvironment remodeling. Clinical evidence highlights significant alterations in the gut and biliary microbial composition of CCA patients, which correlate with tumor stage, vascular invasion, and survival outcomes. Dysregulated BA metabolism in CCA, characterized by accumulation of primary conjugated BAs, promotes tumor invasiveness via interaction with specific BA receptors and fosters an immunosuppressive microenvironment. Emerging therapeutic strategies include antibiotics for pathogenic microbiota modulation, probiotics for microbial homeostasis restoration, fecal microbiota transplantation, and BA pathway modulators. Future directions necessitate integrating synthetic biology (engineered microbiota), multi-omics, and artificial intelligence to develop precision therapies. Targeting the gut-liver axis offers novel therapeutic perspectives for CCA; however, clinical translation demands deeper mechanistic insights and standardized protocols to address challenges such as microbiota heterogeneity and receptor signaling duality.
Keywords: Gut-liver axis, Cholangiocarcinoma, Gut Microbiota, Dysbiosis, Bile salt, therapy, clinical translation
Received: 14 Jun 2025; Accepted: 22 Aug 2025.
Copyright: © 2025 Wang, Qiao, Zheng, Zhang and DONG. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Zhiwei DONG, The Chinese University of Hong Kong, Hong Kong, Hong Kong, SAR China
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