Exploring the correlation among genetic variants, cholecystectomy and gut microbiome: A Mendelian randomization study

Area of Science:

• Genetics
• Microbiology
• Gastroenterology

Background:

• The gut microbiota plays a crucial role in host metabolism and health.
• Alterations in gut microbial composition are linked to various diseases, including gallstone formation.
• The impact of cholecystectomy on gut microbiota composition remains incompletely understood.

Purpose of the Study:

• To investigate the causal relationship between gut microbiota and cholelithiasis using Mendelian randomization.
• To explore the effect of cholecystectomy on the composition of the gut microbiota.

Main Methods:

• Utilized genome-wide association study (GWAS) data for exposures and outcomes.
• Employed inverse variance weighting (IVW) for primary causal estimates.
• Conducted sensitivity analyses including MR-Egger, Egger-intercept, leave-one-out, and MR-PRESSO methods to assess pleiotropy and robustness.

Main Results:

• Several gut genera, including Butyricicoccus and Solibacillus, were found to decrease the risk of cholelithiasis.
• Cholelithiasis occurrence was associated with reduced levels of Blautia and Anaerofilum.
• Post-cholecystectomy, increased levels of Odoribacter and Holdemanella were observed, while Blautia and Butyricicoccus decreased.

Conclusions:

• Specific gut bacteria influence the risk of developing gallstones.
• Cholecystectomy significantly alters gut microbiota composition, impacting digestive function.
• Findings provide a basis for understanding molecular mechanisms in cholelithiasis and post-surgical digestive changes.