Biliary Microbiome Dysbiosis Is Associated with Susceptibility to Post-ERCP Pancreatitis

Background & Aims Pancreatitis remains the most common adverse event following endoscopic retrograde cholangiopancreatography (ERCP), yet current risk stratification relies primarily on clinical and procedural factors. The present study aims to examine bile-based microbiome signatures as a potential link between nonprocedure patient-level risk factor for pancreatitis susceptibility after ERCP. Methods We performed analysis for rates of post-ERCP pancreatitis of a prospective single center cohort of patients undergoing ERCP ( n = 148) with bile collected at the time of the procedure. Microbial profiling was performed using 16S rRNA sequencing. Alpha diversity, beta diversity, differential abundance analyses, and metabolic pathway analysis were evaluated between patients with and without post-ERCP pancreatitis (PEP). Results Patients with PEP demonstrated significantly reduced biliary microbial diversity and distinct composition compared with those without pancreatitis. Differential abundance analysis identified multiple depleted genera in the PEP group. Functional profiling revealed broad reductions in microbial metabolic pathways associated with PEP predominantly involving biosynthetic and central metabolic functions. ROC curve analysis demonstrated that differentially abundant bile microbes can discriminate patients with PEP from those without pancreatitis. Discussion Patients who develop PEP harbor a distinct and functionally depleted biliary microbiome. These findings parallel prior observations of gut dysbiosis in acute pancreatitis and suggest that the biliary microbiome may represent a biologic pathway associated with PEP susceptibility.