Wang Lu, Qiao Weiwei, Zhen Xiaowen, Zhang Yeqiong, Dong Zhiwei
Department of Diagnostics, Second School of Clinical Medicine, Binzhou Medical University, Yantai, Shandong, China.
Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China.
Front Oncol. 2025 Sep 12;15:1646897. doi: 10.3389/fonc.2025.1646897. eCollection 2025.
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.
胆管癌（CCA）是一种侵袭性很强的胆道恶性肿瘤，其发病率呈上升趋势，预后极差。最近的研究表明，肠-肝轴失调通过肠道微生物群失调、胆汁酸（BA）代谢紊乱和免疫微环境重塑推动CCA进展。临床证据突显了CCA患者肠道和胆道微生物组成的显著改变，这些改变与肿瘤分期、血管侵犯和生存结果相关。CCA中失调的BA代谢以初级结合型BA的积累为特征，通过与特定BA受体相互作用促进肿瘤侵袭性，并促进免疫抑制微环境的形成。新兴的治疗策略包括用于调节致病微生物群的抗生素、用于恢复微生物稳态的益生菌、粪便微生物群移植和BA途径调节剂。未来的方向需要整合合成生物学（工程微生物群）、多组学和人工智能来开发精准疗法。靶向肠-肝轴为CCA提供了新的治疗前景；然而，临床转化需要更深入的机制见解和标准化方案，以应对微生物群异质性和受体信号双重性等挑战。
