Abstract
Background
The gut microbiota(GM) plays a significant role in health and disease, with numerous studies confirming its association with various diseases. This study aims to evaluate the genetic causal relationship between GM and ischemic stroke (IS), along with exploring potential blood metabolite-mediated mechanisms.
Methods
Utilizing two-sample Mendelian Randomization (MR) and large-scale Genome-Wide Association Studies (GWAS) data, we investigate the association between GM and IS. Bayesian Weighted MR (BWMR) is employed for validation, and genetic correlations are assessed using Bivariate Linkage Disequilibrium Score Regression (LDSC) and Genetic Analysis Incorporating Pleiotropy and Annotation (GPA).
Results
Our analysis using Inverse Variance Weighted (IVW) method indicates that specific microbial groups, such as genus Ruminiclostridium and order Burkholderiales, are significantly associated with IS risk. Mediation analysis suggests that metabolites like Pyruvate, Arachidonate, and HDL-related lipoproteins may mediate this relationship. Multivariate MR analysis confirms the independence of these mediating effects. Furthermore, both LDSC and GPA analyses demonstrate significant genetic correlations between GM and IS.
Conclusion
Through the integration of various statistical methods and GWAS data, this study provides genetic evidence supporting the causal relationship between GM and IS, uncovering potential biological mediating mechanisms. These findings enhance our understanding of the GM's role in cardiovascular and cerebrovascular diseases, offering insights into preventive and treatment strategies.