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.
Background: Observational studies have revealed the association between some inflammatory cytokines and the occurrence of ischemic stroke, but the causal relationships remain unclear.Methods: We conducted a two-sample Mendelian randomization (MR) analysis to assess the causal effects of thirty inflammatory cytokines and the risk of ischemic stroke. For exposure data, we collected genetic variants associated with inflammatory cytokines as instrumental variables (IVs) from a genome-wide association study (GWAS) meta-analysis from Finland (sample size up to 8,293). For the outcome data, we collected summary data of ischemic stroke from a large-scale GWAS meta-analysis involved 17 studies (34,217 cases and 406,111 controls). We further performed a series of sensitivity analyses as validation of primary MR results.Results: According to the primary MR estimations and further sensitivity analyses, we established one robust association after Bonferroni correction: the odds ratio (95% CI) per unit change in genetically increased IL-4 was 0.84 (0.89–0.95) for ischemic stroke. The chemokine MCP3 showed a nominally significant association with ischemic stroke risk (OR: 0.93, 95% CI: 0.88–0.99, unadjusted p < 0.05). There was no evidence of a causal effect of other inflammatory cytokines and the risk of ischemic stroke.Conclusions: Our study suggested that genetically increased IL-4 levels showed a protective effect on the risk of ischemic stroke, which provides important new insights into the potential therapeutic target for preventing ischemic stroke.
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