A Mendelian randomization and animal study on the causal relationship between gut microbiota and ischemic stroke

Abstract

A growing body of evidence points to a strong link between ischemic stroke and the gut microbiome. Given the wide diversity present in gut microbiota, this research intends to employ advanced and thorough data to investigate the causative relationship between gut microbiota and ischemic stroke. We performed a two-sample study using Mendelian randomization to clarify the causal connection between gut microbiota and ischemic stroke. The GISCOME network encompassed 6,021 individuals with ischemic stroke, primarily of European descent. A total of 473 gut microbial taxa were extracted from the genome-wide association study catalog. The research involved a forward Mendelian randomization approach(gut microbiota as exposure, ischemic stroke as outcome). A variety of analytical techniques were applied, including inverse variance weighting, Weighted Median, MR-Egger, Weighted Mode, and Simple Mode. Following this, a sensitivity analysis was performed to confirm the reliability of our findings. Rats underwent treatment using a middle cerebral artery occlusion model, and after 7 days, stool samples were collected for 16s sequencing to assess changes in gut microbiota and to compare these with the Mendelian randomization results. Our analysis suggests a potential causal association between gut microbiota and ischemic stroke. Through forward causal analysis, relationships of causality between 20 different gut microbial taxa and ischemic stroke were unveiled. Findings from 16s sequencing indicated that there was an overlap of 6 gut microbial taxa with the results of Mendelian randomization. The results of our research indicate a direct link between gut microbiota and ischemic stroke, offering possible direction for upcoming clinical trials.

Keywords: Bacteroides; Clostridiales; Gut microbiota; Ischemic stroke; Mendelian randomization.