Objective To evaluate potential causal associations between genus-level gut microbiota and ischemic stroke (IS) risk using two-sample Mendelian randomization (MR). Methods Public genome-wide association study summary statistics for gut microbiota and IS were used. Single nucleotide polymorphisms associated with genus-level taxa (P<1×10?5) were selected as instrumental variables and processed by linkage disequilibrium clumping, allele harmonization and F-statistic assessment. The inverse-variance weighted (IVW) method was the primary analysis, supplemented by MR-Egger, weighted median, simple mode, weighted mode and sensitivity analyses. Results IVW analysis showed an inverse association between Clostridium innocuum group and IS risk [odds ratio (OR)=0.925, 95% confidence interval (CI) (0.869, 0.985), P=0.015], and Methanobrevibacter [OR=1.069, 95%CI (1.009, 1.132), P=0.023], Senegalimassilia [OR=1.127, 95%CI (1.016, 1.250), P=0.023], Alloprevotella [OR=1.059, 95%CI (1.005, 1.116), P=0.032], Lachnospira [OR=1.181, 95%CI (1.018, 1.371), P=0.029], and Blautia [OR=1.141, 95%CI (1.032, 1.261), P=0.010] were positively associated with IS risk. Sensitivity analyses did not indicate obvious heterogeneity or horizontal pleiotropy. Conclusions Several genus-level gut microbial taxa may be suggestively associated with IS risk. Further validation in independent populations and mechanistic studies are needed.
