Interplay among microbiota, bile acids, and tumor immunity in cholangiocarcinoma: The gut-biliary-liver axis

Cholangiocarcinoma (CCA) is a highly malignant tumor of the biliary tract with a poor prognosis. Currently, specific methods for the early diagnosis and risk stratification if CCA are lacking. With the emergence of the “gut-biliary-liver axis” concept, the intestinal and biliary microbiota are being increasingly recognized to play key roles in the initiation and progression of CCA. This review systematically synthesizes recent clinical and basic research and outlines characteristic patterns of dysbiosis in the feces, bile, and tumor tissues of patients with CCA. It further discusses key mechanisms, including microbiota-bile acid-biliary epithelial signaling, pathogen-associated molecular patterns-mediated chronic inflammation, and immune-metabolic remodeling. It also examines the associations of these mechanisms with tumor progression and treatment responses. On this basis, the review evaluates the potential of intestinal and biliary microbiota and their metabolites as biomarkers for the diagnosis, prognosis, and prediction of the treatment response of CCA. We believe this review demonstrates a theoretical basis for microbiota-targeted precision prevention and therapeutic strategies for the disease.