Gallstone formation and hepatobiliary tumour risk: Clinical implications of the bile acid–gut microbiota axis

Abstract

Background

Gallstones affect approximately 6%–15% of adults worldwide and represent a common condition that also serves as a risk factor for hepatobiliary malignancies. Conventional ultrasound cannot provide early warning during the early metabolic phase before crystallization occurs.

Methods

This narrative review provides a critical synthesis of the mechanisms, clinical evidence, and translational perspectives of the bile acid–gut microbiota axis in gallstone development and hepatobiliary tumour risk. Relevant publications up to September 2026 were identified through searches of MEDLINE/PubMed, EMBASE, and Web of Science, with additional manual screening of reference lists. Randomized clinical trials, systematic reviews, meta-analyses, key mechanistic studies, and guidelines were preferentially included.

Results

Patients with gallstones exhibit characteristic alterations, including elevated serum glycocholic acid (+ 0.83 µmol/L) and taurocholic acid (+ 0.51 µmol/L), reduced microbial diversity (Proteobacteria accounting for 91.59%), and a 2.5 - fold increase in bai gene cluster abundance (r = 0.609). Conjugated bile acids show a dose-response relationship with hepatocellular carcinoma risk (OR = 1.28–5.62), while late breakfast increases gallstone risk (OR = 1.435). The combination of dried blood spot sampling (R² > 0.92) and AI-based prediction models (AUC = 0.82–0.90) offers a feasible approach for dynamic monitoring.

Conclusions

This review proposes a three-tiered stratified management strategy—DBS sampling, targeted metabolomics, and AI assessment—to provide a clinical translational reference for early warning and precision prevention of gallstones and hepatobiliary tumours.