Causal effects of cholecystectomy on the lipidome: cross-sectional and mendelian randomization studies.

BACKGROUND

Cholecystectomy, the surgical removal of the gallbladder, is a widely performed procedure. The gallbladder plays an important role in lipid metabolism, but the effects of its removal on lipidome remains unexplored.

METHODS

This study evaluated the association of cholecystectomy with lipid profiles in two phases. First, a cross-sectional analysis of National Health and Nutrition Examination Survey (NHANES) data employed multivariate linear regression with propensity score matching to compare lipid profiles, including total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG), between individuals with and without a history of cholecystectomy. Second, Mendelian randomization analysis leveraged large-scale GWAS datasets (GWAS Catalog, IEU OpenGWAS, Global Lipids Genetics Consortium) to evaluate causal effects on TC, LDL-C, HDL-C, TG, and 106 lipid-related phenotypes across multicenter cohorts.

RESULTS

NHANES analysis revealed a significant association between cholecystectomy and lower levels of TC (β = - 0.23, 95% CI: - 0.40 to - 0.07, p = 0.009) and LDL-C (β = - 0.30, 95% CI: - 0.46 to - 0.13, p = 0.002), with no significant associations observed for HDL-C or TG. Mendelian randomization analysis further confirmed a causal relationship between cholecystectomy and lower levels of in TC, LDL-C, and 21 related lipid metabolites-including free cholesterol, apolipoprotein B, 14 low-density lipoprotein related metabolites, and 5 intermediate-density lipoprotein related metabolites-all integral to TC and LDL-C metabolism. No causal effects were identified for HDL-C, TG, or their corresponding lipid subtypes.

CONCLUSIONS

Cholecystectomy is robustly associated with lower levels of TC, LDL-C, and 21 related lipid metabolites, with no significant associations observed for TG, HDL-C, or their subtypes. These findings enhance our understanding of the metabolic associations of gallbladder removal and suggest potential cardiovascular benefits.