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=343 026),UAP(n=456 468),MI(n=461 823).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.
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