Cholecystectomy Significantly Alters Gut Microbiota Homeostasis and Metabolic Profiles: A Cross-Sectional Study

Abstract

Cholecystectomy (CCE) is a standard clinical treatment for conditions like gallstones and cholecystitis. However, its link to post-CCE syndrome, colorectal cancer, and nonalcoholic fatty liver disease has raised concerns. Additionally, studies have demonstrated the disruptive effects of CCE on gut microbiota homeostasis and bile acid (BA) metabolism. Considering the role of gut microbiota in regulating host metabolic and immune pathways, the use of dietary and probiotic intervention strategies to maintain a stable gut ecosystem after CCE could potentially reduce associated disease risks. Inter-study variations have made it challenging to identify consistent gut microbiota patterns after CCE, a prerequisite for targeted interventions. In this study, we first meta-analyzed 218 raw 16S rRNA gene sequencing datasets to determine consistent patterns of structural and functional changes in the gut microbiota after CCE. Our results revealed significant alterations in the gut microbiota’s structure and function due to CCE. Furthermore, we identified characteristic gut microbiota changes associated with CCE by constructing a random model classifier. In the validation cohort, this classifier achieved an area under the receiver operating characteristic curve (AUC) of 0.713 and 0.683 when distinguishing between the microbiota of the CCE and healthy groups at the family and genus levels, respectively. Further, fecal metabolomics analysis demonstrated that CCE also substantially modified the metabolic profile, including decreased fecal short-chain fatty acid levels and disrupted BA metabolism. Importantly, dietary patterns, particularly excessive fat and total energy intake, influenced gut microbiota and metabolic profile changes post-CCE. These dietary habits were associated with further enrichment of the microbiota related to BA metabolism and increased levels of intestinal inflammation after CCE. In conclusion, our study identified specific alterations in gut microbiota homeostasis and metabolic profiles associated with CCE. It also revealed a potential link between dietary patterns and gut microbiota changes following CCE. Our study provides a theoretical basis for modulating gut microbiota homeostasis after CCE using long-term dietary strategies and probiotic interventions.