Bile Microbiome and Metabolic Characteristics in Primary Common Bile Duct Stone Patients with Juxtapapillary Duodenal Diverticula: A Clinical Investigation

Objective This study aimed to characterize the bile microbiome and metabolome in patients with common bile duct stones (CBDs), with versus without juxtapapillary duodenal diverticulum (JPDD), to identify potential factors associated with stone formation. Methods From January to May 2024, CBDs patients undergoing endoscopic retrograde cholangiopancreatography at our hospital were prospectively enrolled. Bile samples were collected for 16SrRNA sequencing and LC-MS/MS metabolomics analysis. Patients were divided into JPDD (n = 15) and CBDs (n = 15) groups. Results The JPDD group had larger stone and bile duct diameters (P < 0.05). Although Proteobacteria dominated the bile microbiota in both groups, the JPDD group showed higher abundances of Escherichia–Shigella, Enterococcus, and Escherichia coli. Beta diversity differed significantly between groups (P < 0.05), and LEfSe identified 25 differentially abundant bacterial taxa. Enterococcus, Klebsiella, and Gemellaceae were more abundant in the JPDD group, while Peptococcaceae, Roseburia, and Alistipes were more prevalent in the CBDs group. Enterococcaceae and Enterococcus abundances were positively correlated with stone and duct sizes in the JPDD group (P < 0.05), whereas Peptococcaceae and Acinetobacter showed negative correlations. Metabolomic analysis identified ten differentially enriched pathways—including phenylalanine and alanine metabolism—and higher levels of bilirubin glucuronide and taurochenodeoxycholic acid in the JPDD group. Enterococcus abundance was correlated with bile acid metabolites such as chenodeoxycholylasparagine (P < 0.05). Conclusions JPDD is associated with distinct microbial and metabolic profiles in bile. Enrichment of Enterococcus and Klebsiella in the JPDD group, along with changes in metabolic pathways and bile acid metabolites, suggests a potential link to CBD stone formation and growth.