A Two-sample Mendelian Randomization Study Reveals the Causal Effects of Statin Medication on Gut Microbiota Abundance in the European Population

Background: Observational studies have reported changes in gut microbiota abundance caused by long-term statin medication therapy. However, the causal relation between statin medication and gut microbiota subsets based on genetic variants remains unclear.

Methods: We used genome-wide association study (GWAS) data on statin medication from the FinnGen database and gut microbiota abundance GWAS data from the IEU OpenGWAS project. A Mendelian randomization (MR) analysis was conducted to evaluate the causal effect of statin medication on gut microbiota abundance using the inverse variance weighting (IVW) method, MR-Egger regression, and weighted median approach. Meanwhile, heterogeneity and pleiotropy analyses were also undertaken in this study.

Results: Statin medication was negatively correlated with five species of gut microbiota abundance: (Beta = -0.2745, 95% CI = (-0.4422, -0.1068), and = 0.0013), (Beta = -0.1904, 95% CI = (-0.3255, -0.0553), and = 0.0057), (Beta = -0.1212, 95% CI = (-0.2194, -0.0231), and = 0.0154), (Beta = -0.1149, 95% CI = (-0.2238, -0.0060), and = 0.0385), and (Beta = -0.0970, 95% CI = (-0.2238, 0.0060), and = 0.0400) and positively correlated with one species of gut microbiota: (Beta = 0.2452, 95% CI = (0.0299, 0.4606), and = 0.0255). In addition, no significant heterogeneity or pleiotropy was detected in the abovementioned gut microbiota.

Conclusion: This Mendelian randomization analysis indicates a causal relationship between statin medication and six gut microbiota species. These findings may provide new strategies for health monitoring in populations taking long-term statin medications.