Multi-omics analysis reveals dynamic changes in gut microbiota and metabolites associated with cholecystectomy and post-cholecystectomy diarrhea

Cholecystectomy perturbs bile acid homeostasis and gut microbiota stability, elevating time-dependent disease risks. Short-term manifestations primarily linked to post-cholecystectomy diarrhea (PCD), while long-term demonstrating increased propensity for metabolic and immune-related disorders. However, the dynamic changes in gut microbiota and key microorganisms promoting PCD remain unelucidated after cholecystectomy. Our study aims to dissect the time-resolved mechanisms through which cholecystectomy disrupts gut microbiota-metabolic homeostasis to initiate PCD, identify stage-specific microbial biomarkers predicting postoperative risk transition, and delineate the physiological significance of dietary adaptations in restoring intestinal equilibrium. We have established a longitudinal observational cohort (n ​= ​35 for cholecystectomy, n ​= ​13 for healthy controls) and utilized metagenomics and metabolomics to examine the dynamic changes in gut microbiota, metabolic pathways, and metabolites in patients after cholecystectomy, as well as in those experiencing PCD diarrhea. Post-cholecystectomy, we observed persistent intestinal inflammation elevation. Key species involved in immune and metabolic regulation, such as Ruminococcus gnavus , Bacteroides cellulosilyticus , Megamonas funiformis , and Parabacteroides distasonis , were identified. Fecal bile acids (deoxycholic, lithocholic) increased significantly within six months, while short-chain fatty acids (acetic, butyric) decreased in subsequent years, with these coordinated shifts potentially serving as contributing factors to intestinal disorders after cholecystectomy. Importantly, dietary modulation after cholecystectomy, particularly an increased intake of red meat, may further disrupt intestinal health via the gut microbiota-bile acid axis. Enrichment of Ruminococcus gnavus and altered phenylalanine/tyrosine metabolism shortly after surgery were typical of PCD patients. In summary, both cholecystectomy and PCD are accompanied by complex alterations in gut microbiota and metabolism. These key species impact the occurrence of intestinal inflammation and diarrhea through multiple pathways. Our findings establish a foundation for preventing post-cholecystectomy complications through dietary modifications or probiotic interventions.