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

Abstract Objective This study investigates the microbiological and metabolic characteristics of bile in patients with common bile duct stones (CBDs) with and without juxtapapillary duodenal diverticulum (JPDD) to analyze stone formation causes and influencing factors. 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). 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 (P < 0.05). LEfSe analysis identified 25 differential bacterial species. Enterococcus, Klebsiella, and Gemellaceaeke were enriched in the JPDD group, while Peptococcaceae, Roseburia, and Alistipes were enriched in the CBDs group (P < 0.05). Enterococcaceae and Enterococcus correlated positively with bile duct and stone size in the JPDD group (P < 0.05). Peptococcaceae and Acinetobacter showed negative correlations (P < 0.05). Ten metabolic pathways, including phenylalanine and alanine metabolism, differed significantly (P < 0.05). Metabolites like bilirubin glucuronide and taurochenodeoxycholic acid were upregulated in the JPDD group. Enterococcus in the JPDD group correlated with bile acid metabolites like chenodeoxycholylasparagine (P < 0.05). Conclusions JPDD influences CBD stone formation and size. JPDD alters bile microbiota, with Enterococcus and Klebsiella enriched in the JPDD group, and Peptococcaceae in the CBDs group. These microbiota correlate with stone size. JPDD changes bile metabolism, with metabolites like taurochenodeoxycholic acid and altered metabolic pathways influencing stone formation.