Abstract

Background

Increasing evidence implicates the microbiome as a susceptibility factor for ischemic stroke (IS). Interpretation of this evidence is difficult for the composition of the microbiome is influenced by various factors and might affect differently in IS subtypes. We aim to determine if the specific gut microbiome is causally associated with IS subtypes and suggest potential approaches for stroke prevention.

Methods

We conducted a two-sample Mendelian Randomization analysis to test the causal relationship between gut microbiome and IS subtypes. For exposure data, we extracted genetic variants associated with 194 bacterial traits from MiBioGen consortium (N = 18,340). For outcomes, we selected three IS subtypes including cardioembolic stroke (CES, N = 410,484), small vessel stroke (SVS, N = 198,048), and large artery stroke (LAS, N = 198,048). Additionally, we performed a sequence of sensitivity analyses to validate preliminary MR results.

Results

There were four, three, and four bacteria showing an increased risk for LAS, SVS, and CES, respectively, and there were five, six, and five bacteria leading a decreasing risk for LAS, SVS, and CES, respectively. Among these, the genus_Intestinimonas showed negative associations with LAS [odds ratio (OR) = 0.77, 95% confidence interval (CI) (0.61-0.98)] and SVS (0.85, 0.73-0.98). The genus_LachnospiraceaeNK4A136group was genetically associated with decreased risk of both SVS (0.81, 0.66-0.99) and CES (0.75, 0.60-0.94).

Conclusions

The study revealed the causal effect of the abundance of specific bacterial features on the risk of IS subtypes. Notably, genus_Intestinimonas and genus_LachnospiraceaeNK4A136group displayed significant protection against more than one IS subtype, further suggesting potential applications of targeted probiotics in IS prevention.