肠道菌群与缺血性心脏病两样本双向多变量孟德尔随机化研究  

To analyze the causal relationship between gut microbiota and ischemic heart disease by two-sample bidirectional multivariate Mendelian randomization

作　　者：郑东东 于睿[2] 赵宏月 张东伟[3] 段盈竹 梁健 张欢[5] 倪萍 于游[7] Zheng Dongdong;Yu Rui;Zhao Hongyue;Zhang Dongwei;Duan Yingzhu;Liang Jian;Zhang Huan;Ni Ping;Yu You(Emergency Centre,Shenben Branch,the Affiliated Hospital of Liaoning University of Traditional Chinese Medicine/Liaoning University of Traditional Chinese Medicine,Shenyang 110847,China)

机构地区：[1]辽宁中医药大学/辽宁中医药大学附属医院沈本院区急诊中心,辽宁沈阳110847 [2]辽宁中医药大学科研处,辽宁沈阳110847 [3]辽宁中医药大学附属医院沈本内二科,辽宁沈阳110031 [4]辽宁中医药大学研究生院,辽宁沈阳110847 [5]辽宁中医药大学护理学院,辽宁沈阳110847 [6]辽宁中医药大学第一临床学院,辽宁沈阳110847 [7]辽宁中医药大学附属第二医院心病二科,辽宁沈阳110034

出　　处：《中国急救医学》2025年第1期9-16,共8页Chinese Journal of Critical Care Medicine

基　　金：国家自然科学基金项目(82274494);辽宁省科学技术计划项目(2020JH1/10100022);辽宁省科学技术计划项目(2023JH2/101600030);辽宁省教育厅人文社会科学研究服务地方项目(L202074)。

摘　　要：目的探索肠道菌群与缺血性心脏病(IHD)[稳定型心绞痛(stable angina pectoris,SAP)、不稳定型心绞痛(unstable angina pectoris,UAP)、心肌梗死(myocardial infarction,MI)]潜在的因果关系。方法从MiBioGen联盟中提取211种肠道菌群,从IEU Open GWAS数据库中选择三种IHD数据:SAP(n=343026)、UAP(n=456468)、MI(n=461823)。采用逆方差加权法(IVW)进行两样本双向多变量孟德尔随机化(Mendelian randomization,MR)分析,通过敏感性分析验证MR结果的可靠性。结果有10种菌群与SAP、UAP、MI存在显著因果关系。其中The order.Gastranaerophilales(OR=1.09,95%CI 1.01~1.17,P=0.022)和family.FamilyXI(OR=1.10,95%CI 1.04~1.17,P=0.001)是SAP的危险因素,α-变形菌纲(OR=1.20,95%CI 1.04~1.38,P=0.013)和family.FamilyXI(OR=1.10,95%CI 1.02~1.20,P=0.016)是UAP的危险因素,氨基酸球菌科(OR=0.80,95%CI 0.68~0.95,P=0.009)是UAP的保护因素,疣微菌纲、疣微菌科、疣微菌目和阿克曼氏菌属(OR=0.90,95%CI 0.82~0.99,P=0.048)是MI的保护因素,红螺菌科(OR=1.11,95%CI 1.04~1.20,P=0.002)是MI的危险因素。敏感度分析显示无多效性和异质性。反向MR未发现潜在的因果关系。多变量MR表明,在同时调整高血压、糖尿病、体重指数(BMI)后,氨基酸球菌科仍保持降低UAP的发病风险。结论本研究采用遗传学方法验证了肠道菌群与IHD的关联性,并提供进一步研究的菌群信息。Objective To explore the potential causal relationship between gut microbiota and ischemic heart disease(IHD)[stable angina pectoris(SAP),unstable angina pectoris(UAP),myocardial infarction(MI)].Methods Two hundred and eleven types of gut microbiota were extracted from the MiBioGen Alliance,the data of three IHDs were selected from the IEU Open GWAS database:SAP(n=343026),UAP(n=456468),MI(n=461823).Two-sample bidirectional multivariate Mendelian randomization(MR)analysis was conducted by using inverse-variance weighted(IVW)and the reliability of the MR results was verified by sensitivity analysis.Results A total of 10 bacterial groups were causally associated with SAP,UAP and MI.Among them,the order.Gastranaerophilales(OR=1.09,95%CI 1.01-1.17,P=0.022)and family.FamilyXI(OR=1.10,95%CI 1.04-1.17,P=0.001)were the risk factors for SAP.Alpha-proteobacteria(OR=1.20,95%CI 1.04-1.38,P=0.013)and family.FamilyXI(OR=1.10,95%CI 1.02-1.20,P=0.016)were risk factors for UAP,and family.Aminococcaceae(OR=0.80,95%CI 0.68-0.95,P=0.009)was a protective factor for UAP.Verrucomicrobiae,family.Verrucomicrobiaceae,order.Verrucomicrobiales and genus.Akkermansia(OR=0.90,95%CI 0.82-0.99,P=0.048)were protective factors for MI,and Rhodospirillaceae(OR=1.11,95%CI 1.04-1.20,P=0.002)was a risk factor for MI.Sensitivity analysis showed no pleiotropy or heterogeneity.Reverse MR did not reveal a potential causal relationship.Multivariate MR showed that Aminococcaceae maintained to reduce the risk of UAP after simultaneous adjustment for hypertension,diabetes and body mass index(BMI).Conclusions This study uses a genetic approach to validate the association between gut microbiota and IHD and provides microbial information that can be used for further research.

关 键 词：孟德尔随机化 肠道菌群 稳定型心绞痛 不稳定型心绞痛 心肌梗死 

分 类 号：R541[医药卫生—心血管疾病]