质子泵抑制剂与缺血性脑卒中的因果关系及肠道微生物紊乱的中介效应*

doi:10.3870/j.issn.1672-0741.25.11.003

华中科技大学学报（医学版） ›› 2026, Vol. 55 ›› Issue (3): 309-318.doi: 10.3870/j.issn.1672-0741.25.11.003

• 论著 • 下一篇

质子泵抑制剂与缺血性脑卒中的因果关系及肠道微生物紊乱的中介效应^*

李筱婷^1,2, 王超群^1,3, 高义昆^1,2, 叶樱泽⁴, 古丽娟^1△

武汉大学人民医院 ¹中心实验室 ²麻醉科 ³神经外科,武汉 430060
⁴华中科技大学同济医学院附属同济医院麻醉学与疼痛医学科,武汉 430030

收稿日期:2025-11-04 出版日期:2026-06-15 发布日期:2026-06-17
通讯作者: ^△E-mail:gulijuan@shu.edu.cn
作者简介:李筱婷,女,2000年生,硕士研究生,E-mail:lsiaoting@163.com
基金资助:
^*国家自然科学基金资助项目(No.82471370)

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

Li Xiaoting^1,2, Wang Chaoqun^1,3, Gao Yikun^1,2 et al

¹Central Laboratory, ²Department of Anesthesiology, ³Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan 430060, China

Received:2025-11-04 Online:2026-06-15 Published:2026-06-17
Contact: ^△E-mail:gulijuan@shu.edu.cn

摘要/Abstract

摘要： 目的探讨质子泵抑制剂(PPI)使用与缺血性脑卒中(IS)之间的因果关系,并评估肠道微生物群在上述关联中的潜在中介作用。方法本研究采用孟德尔随机化(MR)方法,与常用PPI(埃索美拉唑、兰索拉唑、奥美拉唑、雷贝拉唑)相关的单核苷酸多态性(SNPs)作为工具变量,分析PPI使用与IS的因果关联;进一步采用两步孟德尔随机化(two-step MR)方法,评估肠道微生物群在PPI与IS关联中的潜在中介效应。结果研究发现,埃索美拉唑和兰索拉唑与大动脉粥样硬化性卒中(LAS)发生风险之间存在提示性关联;尽管使用上述PPI后观察到肠道微生物群的特定改变,但这些改变并未中介其对LAS风险的增加,提示PPI与LAS的关联并非主要由微生物群改变驱动。结论该研究结果提示,作为临床最常用处方药之一的PPI或为心血管疾病发生的危险因素,为IS的预防与治疗提供了新的启示。

关键词: 缺血性脑卒中, 大动脉粥样硬化性脑卒中, 质子泵抑制剂, 肠道微生物群, 孟德尔随机化

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

中图分类号:

R743.3

李筱婷, 王超群, 高义昆, 叶樱泽, 古丽娟. 质子泵抑制剂与缺血性脑卒中的因果关系及肠道微生物紊乱的中介效应^*[J]. 华中科技大学学报（医学版）, 2026, 55(3): 309-318.

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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质子泵抑制剂与缺血性脑卒中的因果关系及肠道微生物紊乱的中介效应^*

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

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