Causal relationship between gut microbiota and atherosclerosis:a two-sample Mendelian randomization study
Objective To explore the causal relationship between gut microbiota and atherosclerosis by Mendelian randomization(MR).Methods The human gut microbiota dataset was downloaded from the MiBioGen database,and 196 known bacterial communities were retained as exposure factors.The instrumental variables were single nucleotide polymorphisms(SNPs)that were strongly correlated with the exposure factors and independent of each other.The outcome variable was an atherosclerosis dataset containing 10 006 patients and 446 342 controls downloaded from the genome-wide association study database.Two-sample MR analysis was performed using the inverse variance weighted(IVW)method,weighted median method,and MR-Egger test,respectively.The odds ratio(OR)was used to evaluate the causal association between gut microbiota and atherosclerosis.Sensitivity analysis was performed using the leave-one-out method,horizontal pleiotropy was tested using the MR-Egger intercept test and the MR-PRESSO global test,and heterogeneity was tested using the Cochran Q method.Two-sample MR analysis was performed using the inverse variance weighted(IVW)method,weighted median method,and MR-Egger test,respectively.The odds ratio(OR)was used to evaluate the causal association between gut microbiota and atherosclerosis.Sensitivity analysis was performed using the leave-one-out method,horizontal pleiotropy was tested using the MR-Egger intercept test and the MR-PRESSO global test,and heterogeneity was tested using the Cochran Q method.Results A total of 9 types of bacteria were found to be causally associated with the onset of atherosclerosis(P＜0.05),and 402 SNPs were included.The results of IVW analysis showed that Actinomycetes[OR=2.311,95％confidence interval(CI)(1.546,2.911),P＜0.001],Christensenaceae[OR=1.956,95％CI(1.194,3.099),P=0.024],Lachnospiraceae[OR=1.793,95％CI(1.192,2.561),P＜0.001],Bacilales[OR=1.769,95％CI(1.320,2.371),P＜0.001]and Firmicutes[OR=2.399,95％CI(1.597,3.247),P=0.028]were positively correlated with atherosclerosis;Ruminococcaceae[OR=0.447,95％CI(0.300,0.667),P=0.0031],Desulfovibrioles[OR=0.165,95％CI(0.065,0.416),P＜0.001],Faecalibacterium[OR=0.246,95％CI(0.122,0.495),P＜0.001],and Cyanobacteria[OR=0.249,95％CI(0.164,0.376),P＜0.001]were negatively correlated with atherosclerosis.In addition,the leave-one-out analysis suggested that the results were stable,and no horizontal pleiotropy and heterogeneity were found.Conclusion There is a causal relationship between intestinal microbiota and atherosclerosis.Increased abundance of Actinomycetes,Christensenaceae,Lachnospiraceae,Bacillusales,and Firmicutes can increase the risk of atherosclerosis,while increased abundance of Ruminococcaceae,Desulfovibrioales,Faecalibacterium,and Cyanobacteria can reduce the risk of atherosclerosis.
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