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.