Causal Effects of Gut Microbiome on Cardiovascular diseases: A Two-Sample Mendelian Randomization Study

Abstract

Abstract Background: Cardiovascular diseases (CVDs) are the leading cause of death globally, taking an estimated 17.9 million lives each year. More evidence has shown that gut microbiota influences the three diseases through metabolites, the observational association between the gut microbiome, cardiovascular and cerebrovascular diseases has been well documented. However, whether there is a causal relationship with this association remains unclear. Methods: Basing publicly available GWAS aggregated data, a two-sample Mendelian randomization (MR) was used to examine the causal relationship between the gut microbiome, cardiovascular and cerebrovascular diseases. Two sets of MR analyses were performed. A set of single nucleotide polymorphisms (SNPs) less than the genome-wide statistical significance threshold (5×10-5) is used as the instrumental variable. Results: Based on the significance level of locus range, the results showed that there was a causal effect of gut microbial composition on the risk of MI, CI, and CAD. The inverse variance weighted (IVW) method shows that Alphaproteobacteria, Clostridialesvadin-BB60groupand Oxalobacteraceae were risk factors for MI, yet FamilyXIII was protective factor. Coriobacteriales, Verrucomicrobiales，ClostridialesvadinBB60groupwere risk factors for CI, while Actinobacteria, Gammaproteobacteria, Verrucomicrobiae, Enterobacteriales, Enterobacteriaceae, Methanobacteriaceae, Prevotellaceae were protective factors. And Actinomycetaceae was positively related with the risk of CAD, while Gammaproteobacteria and Actinomycetaleswere negatively related with it. Actinobacteria, Proteobacteria and ClostridialesvadinBB60group could casually related with CVDs. Conclusion: Our MR Analysis showed a causal relationship between gut microbiome and CVDs, which may help provide new insights into mechanisms underlying of CVDs.