Metagenomic Profiling of Gut Microbiome in Post-cholecystectomy Patients with Diarrhea: A Nested Case-control Study

Background Cholecystectomy can cause diarrhea, with an incidence as high as 57.2%, seriously impacting patient prognosis. To investigate the gut dysbiosis following cholecystectomy and identify microbial biomarkers and functional genomics associated with post-cholecystectomy diarrhea (PCD), we conducted a nested case-control study within a prospective cohort. Methods We enrolled a cohort of 160 patients. At follow-up completion, 30 patients who developed PCD were matched with 30 non-PCD (NPCD) controls. 16S rRNA sequencing analyzed gut microbiota structure and diversity. Representative fecal samples underwent metagenomic sequencing for species level and genetic differential analysis. Results The potentially pathogenic bacteria Coprococcus _ comes and Blautia _ sp. were found to be significantly enriched in the gut microbiota of PCD patients, with their abundance positively correlated with the degree of intestinal inflammation. In contrast, the potentially beneficial bacterial species Bacteroides intestinalis and Prevotella copri , known to contribute to lipid metabolism and play a role in modulating gut immunity and suppressing inflammatory responses, were found to be significantly depleted in PCD patients. Further functional analysis revealed that the gut microbiota of PCD patients was significantly enriched in gene pathways related to cell motility, membrane transport and sulphur metabolism. Conclusions This work identified potential beneficial and pathogenic bacterial species associated with the onset of PCD, as well as significantly enriched functional pathways within the intestinal microbiota. These findings provide a scientific basis for elucidating the relationship between PCD and gut microbiota, and offer valuable insights for developing microbiota-targeted interventions to alleviate PCD symptoms.