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. 2024 Dec 13:15:1380830.
doi: 10.3389/fgene.2024.1380830. eCollection 2024.

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

Peng Zhou #  1   2 , Chen Qiu #  1 , Zequn Zhuang #  3 , Kaihang Shi #  4 , Zhihui Yang  2 , Yuyan Ding  2 , Huiheng Qu  2 , Jiazeng Xia  1   2
Affiliations

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

Peng Zhou et al. Front Genet. .

Abstract

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: Parabacteroides (BetaIVW = -0.2745, 95% CI = (-0.4422, -0.1068), and P IVW = 0.0013), Ruminococcaceae UCG-009 (BetaIVW = -0.1904, 95% CI = (-0.3255, -0.0553), and P IVW = 0.0057), Coprococcus 1 (BetaIVW = -0.1212, 95% CI = (-0.2194, -0.0231), and P IVW = 0.0154), Ruminococcaceae UCG-010 (BetaIVW = -0.1149, 95% CI = (-0.2238, -0.0060), and P IVW = 0.0385), and Veillonellaceae (BetaIVW = -0.0970, 95% CI = (-0.2238, 0.0060), and P IVW = 0.0400) and positively correlated with one species of gut microbiota: Desulfovibrio (BetaIVW = 0.2452, 95% CI = (0.0299, 0.4606), and P IVW = 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.

Keywords: Mendelian randomization; causal effect; gut microbiota; statin medication; two-sample Mendelian randomization.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Design and flowchart of this study.
FIGURE 2
FIGURE 2
(A–F) Scatterplot showing the results of the MR analysis on the association between statin medication and gut microbiota abundance.
FIGURE 3
FIGURE 3
(A–F) Funnel plot illustrating the association between statin medication and gut microbiota abundance.
FIGURE 4
FIGURE 4
(A–F) Leave-one-out analysis of the association between statin medication and gut microbiota abundance.
See this image and copyright information in PMC

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