Causal Association Between Proton Pump Inhibitors and Ischemic Stroke and the Mediating Effect of Gut Microbiota Homeostasis Disruption

doi:10.3870/j.issn.1672-0741.25.11.003

Abstract

Abstract: Objective To investigate the causal association between proton pump inhibitor(PPI)use and ischemic stroke(IS),and to evaluate the potential mediating role of gut microbiota in the aforementioned association. Methods Mendelian randomization(MR)method was employed,with single nucleotide polymorphisms(SNPs)associated with commonly used PPI(esomeprazole,lansoprazole,omeprazole,rabeprazole)as instrumental variables,to analyze the causal relationship between PPI use and IS.Furthermore,a two-step Mendelian randomization(two-step MR)method was used to assess the potential mediating effect of gut microbiota in the association between PPI and IS. Results The results of this study showed both esomeprazole and lansoprazole had a significant causal association with the risk of large artery atherosclerotic stroke(LAS).Although specific changes in gut microbiota were observed after the application of the aforementioned PPI,these changes did not mediate the increasing effect on LAS risk,suggesting that the association between PPI and LAS is not mainly mediated by changes in gut microbiota. Conclusion This finding indicates that PPI,as one of the most commonly used prescription drugs in clinical practice,may be a potential risk factor for cardiovascular diseases,providing a new theoretical basis and research direction for the prevention,diagnosis and treatment of IS.

Key words: ischemic stroke, large artery atherosclerotic stroke, proton pump inhibitors, gut microbiota, Mendelian randomization

CLC Number:

R743.3

Li Xiaoting, Wang Chaoqun, Gao Yikun et al. Causal Association Between Proton Pump Inhibitors and Ischemic Stroke and the Mediating Effect of Gut Microbiota Homeostasis Disruption[J]. Acta Medicinae Universitatis Scientiae et Technologiae Huazhong, 2026, 55(3): 309-318.

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