Introduction

Recurrent bile duct stones (RBDS) develop in up to 20% of patients after successful endoscopic clearance of initial stones. While anatomical and procedural risk factors are well recognized, the role of bile acid composition and bile microbiota in RBDS has gained attention. Bile acids, critical for cholesterol solubilization and intestinal homeostasis, may undergo deconjugation or biotransformation when exposed to intestinal flora via duodenobiliary reflux, altering their physicochemical properties and promoting lithogenicity.

Aims & Methods

We aimed to investigate whether alterations in bile acid composition and microbial colonization are associated with stone recurrence. A total of 184 patients who underwent biliary drainage at Konyang University Hospital (2019–2022) were enrolled. Patients were categorized into First Diagnosis Group (n=155) and Recurrence Group (n=29). Bile was aspirated after ERCP or PTBD, and 15 bile acids (5 unconjugated, 10 conjugated) were quantified using HPLC-MS/MS. Bile cultures were analyzed for microbial composition. Statistical comparisons were made using independent t-tests and chi-square analysis.

Results

Patients with RBDS were significantly older (77.8 vs. 69.0 years, P=0.005). Total bile acid concentration was lower in the Recurrence Group (4734 vs. 5902 ppm, P=0.083). Conjugated bile acids—including T-CA, T-DCA, G-CA, G-DCA, and G-LCA—were significantly reduced (P<0.05). Taurine-conjugated bile acids showed a marked decline (1326 vs. 1876 ppm, P=0.041). Primary bile acids were lower in the Recurrence Group (3272 vs. 4339 ppm, P=0.035), while the primary-to-secondary bile acid ratio was significantly decreased (3.29 vs. 7.35, P=0.001), indicating a shift toward hydrophobic bile.
Microbiologically, Enterococcus spp. were significantly more prevalent in the Recurrence Group (76% vs. 30%, P<0.001), particularly E. faecalis, E. casseliflavus, and E. gallinarum. Notably, E. faecalis possesses bile salt hydrolase (BSH) activity that can deconjugate bile acids, promoting accumulation of hydrophobic, poorly soluble forms. This aligns with the observed increase in unconjugated LCA and DCA.

Conclusion

Recurrent bile duct stone patients exhibit reduced levels of conjugated and primary bile acids and increased prevalence of bile-resident Enterococcus spp., known for bile salt hydrolase activity. These changes may lead to deconjugation, increased hydrophobicity, and impaired micelle formation, contributing to bile lithogenicity. These findings support the potential utility of bile acid profiling and bile microbiota analysis as predictive and preventive tools in RBDS management.

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