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

Peng Zhou; Chen Qiu; Zequn Zhuang; Kaihang Shi; Zhihui Yang; Yuyan Ding; Huiheng Qu; Jiazeng Xia

doi:10.3389/fgene.2024.1380830

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

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

Authors

Peng Zhou^#^{1

2}, Chen Qiu^#¹, Zequn Zhuang^#³, Kaihang Shi^#⁴, Zhihui Yang², Yuyan Ding², Huiheng Qu², Jiazeng Xia^{1

2}

Affiliations

¹ Department of General Surgery, The Affiliated Wuxi No.2 People's Hospital of Nanjing Medical University, Wuxi Medical Center, Nanjing Medical University, Wuxi, Jiangsu, China.
² Department of General Surgery, Institute of General Surgical Research, Jiangnan University Medical Center, School of Medicine, Jiangnan University, Wuxi, China.
³ Department of Hepatobiliary Surgery, Jinjiang Municipal Hospital (Shanghai Sixth People's Hospital Fujian), Quanzhou, Fujian, China.
⁴ Department of Hepatobiliary Surgery, The Affiliated Yixing Hospital of Jiangsu University, Wuxi, China.

^# Contributed equally.

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

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This work was supported by the Key Project of Scientific Research from Jiangsu Commission of Health (ZDB2020026); Wuxi Taihu Lake Talent Plan, Team in Medical and Health Profession (THRC0003); Wuxi Medical Key Discipline Construction Project, Medical Development Discipline (FZXK2021009); Wuxi Science and Technology Development Fund from Wuxi Science and Technology Bureau (N20201002); and Postgraduate Research and Practice Innovation Program of Jiangsu Province (SJCX23_0690).