Causal Effects of the Gut Microbiota on Cerebral Infarction: A Two-Sample Mendelian Randomization Study

Abstract— Emerging evidence suggests that the gut microbiota plays a significant role in the development of cerebral infarction (CI), yet the causative connections involved remain poorly defined. This study aimed to establish a causal relationship between the gut microbiota and CI by identifying specific microbial taxa through genome-wide association study (GWAS) summary statistics-based two-sample Mendelian randomization (MR) analysis. The most extensive GWAS data on the gut microbiota were sourced from the MiBioGen consortium, while CI-related summary data were derived from the IEU open GWAS database. The inverse variance weighted (IVW) method was employed to assess causality, with subsequent pleiotropy and heterogeneity tests to validate the findings. IVW analysis identified nine bacterial taxa nominally associated with CI risk. Protective associations were detected for genus Ruminococcus torques group (p  =  0.016), family Clostridia lesvad in BB60 group (p  =  0.036), an unknown genus id.1000000073 (p  =  0.036), family Rhodospirillaceae (p  =  0.041), and genus Erysipelotrichaceae UCG003 (p  =  0.045). Conversely, the family Peptococcaceae (p  =  0.016), genus Fusicatenibacter (p  =  0.027), genus Ruminococcaceae UCG010 (p  =  0.032), and genus Eubacterium brachy group (p  =  0.032) were linked to an increased risk of CI. No evidence of pleiotropy or heterogeneity was found, supporting the robustness of these associations. These MR analysis findings indicate a causal link between specific gut microbiota and CI, providing new insights into the microbial mechanisms influencing CI and potential therapeutic targets.