上海交通大学学报（医学版）2025，Vol.45Issue(12)：1606-1619,14.DOI:10.3969/j.issn.1674-8115.2025.12.006
肠道微生物群与心血管疾病的因果关系评价:双向孟德尔随机化分析
Causal relationship between gut microbiota and cardiovascular diseases:a bidirectional Mendelian randomization analysis
摘要
Abstract
Objective·To investigate the causal relationship between gut microbiota and cardiovascular diseases(CVDs)using Mendelian randomization(MR).Methods·Instrumental variables included genetic loci from gut microbiota data provided by the MiBioGen consortium(n=18 340)and CVD data from the IEU Open GWAS database,covering four CVD types:atrial fibrillation(n=1 030 836),coronary artery disease(n=547 261),hypertension(n=20 526),and heart failure(n=977 323).The inverse variance weighted(IVW)method was employed as the primary analytical approach.Additionally,Cochran's Q test was used to assess heterogeneity of genetic instruments,the MR-Egger intercept test to evaluate horizontal pleiotropy,and leave-one-out analysis to examine the sensitivity of single-nucleotide polymorphisms(SNPs)on the exposure-outcome causal relationship.The MR Steiger test was applied to validate the causal direction between gut microbiota and CVDs.Results·The IVW analysis indicated that Victivallales(OR=0.939),Howardella(OR=0.939),Anaerostipes(OR=0.922),Bifidobacteriaceae(OR=0.916),Lentisphaeria(OR=0.936),Odoribacter(OR=0.909),Intestinibacter(OR=0.933),Lentisphaerae(OR=0.926),and Bifidobacteriales(OR=0.916)were protective factors against atrial fibrillation,while Catenibacterium(OR=1.057),Lachnospiraceae UCG008(OR=1.051),Streptococcus(OR=1.089),and Victivallis(OR=1.038)were risk factors.For coronary artery disease,Lactobacillales(OR=0.919)and Parabacteroides(OR=0.866)were protective factors,while Veillonellaceae(OR=1.065),Lachnoclostridium(OR=1.093),Lachnospiraceae(OR=1.094),Oxalobacter(OR=1.062),and Odoribacter(OR=1.160)were risk factors.For hypertension,Mollicutes RF9(OR=0.851),Coriobacteriia(OR=0.803),Coriobacteriales(OR=0.803),Coriobacteriaceae(OR=0.803),and Intestinibacter(OR=0.819)were protective factors,while Christensenellaceae R7 group(OR=1.218),Desulfovibrio(OR=1.167),and Peptococcaceae(OR=1.230)were risk factors.For heart failure,Bacillales(OR=0.955)and Anaerostipes(OR=0.899)were protective factors,while Ruminococcus UCG009(OR=1.107),Eubacterium oxidoreducens group(OR=1.117),Selenomonadales(OR=1.106),Negativicutes(OR=1.107),Eubacterium eligens group(OR=1.139),and Flavonifractor(OR=1.144)were risk factors.Cochran's Q test showed no heterogeneity among SNPs of gut microbiota causally associated with CVDs(all P>0.05).The pleiotropy test found no evidence of horizontal pleiotropy(all P>0.05).Leave-one-out sensitivity analysis confirmed the robustness of the results.The MR Steiger directionality test supported the causal direction from gut microbiota(exposure)to CVDs(outcome).Conclusion·Some gut microbiota have significant causal effects on CVDs;altering their abundance may influence CVD risk,providing potential targets for microbiota-based intervention strategies.关键词
肠道微生物群/心血管疾病/孟德尔随机化/全基因组关联分析/单核苷酸多态性Key words
gut microbiota/cardiovascular disease/Mendelian randomization/genome-wide association study(GWAS)/single-nucleotide polymorphism(SNP)分类
医药卫生引用本文复制引用
马会华,闫奎坡,刘刚,徐亚洲,张磊,孙彦琴..肠道微生物群与心血管疾病的因果关系评价:双向孟德尔随机化分析[J].上海交通大学学报（医学版）,2025,45(12):1606-1619,14.基金项目
河南省中医药科学研究专项课题(2016ZY3003,2021JDZX038,2017ZY2017). Henan Province Specialized Research Fund for Traditional Chinese Medicine Science(2016ZY3003,2021JDZX038,2017ZY2017). （2016ZY3003,2021JDZX038,2017ZY2017）
