A two-sample Mendelian randomization study reveals the causal effects of statin medication on gut microbiota abundance in the European population

BackgroundObservational 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.MethodsWe used genome-wide association study (G...

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Main Authors: Peng Zhou, Chen Qiu, Zequn Zhuang, Kaihang Shi, Zhihui Yang, Yuyan Ding, Huiheng Qu, Jiazeng Xia
Format: Article
Language:English
Published: Frontiers Media S.A. 2024-12-01
Series:Frontiers in Genetics
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Online Access:https://www.frontiersin.org/articles/10.3389/fgene.2024.1380830/full
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Summary:BackgroundObservational 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.MethodsWe 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.ResultsStatin medication was negatively correlated with five species of gut microbiota abundance: Parabacteroides (BetaIVW = −0.2745, 95% CI = (−0.4422, −0.1068), and PIVW = 0.0013), Ruminococcaceae UCG-009 (BetaIVW = −0.1904, 95% CI = (−0.3255, −0.0553), and PIVW = 0.0057), Coprococcus 1 (BetaIVW = −0.1212, 95% CI = (−0.2194, −0.0231), and PIVW = 0.0154), Ruminococcaceae UCG-010 (BetaIVW = −0.1149, 95% CI = (−0.2238, −0.0060), and PIVW = 0.0385), and Veillonellaceae (BetaIVW = −0.0970, 95% CI = (−0.2238, 0.0060), and PIVW = 0.0400) and positively correlated with one species of gut microbiota: Desulfovibrio (BetaIVW = 0.2452, 95% CI = (0.0299, 0.4606), and PIVW = 0.0255). In addition, no significant heterogeneity or pleiotropy was detected in the abovementioned gut microbiota.ConclusionThis 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.
ISSN:1664-8021