Causal Associations Between Gut Microbiota and Cerebrovascular Diseases

Abstract

BackgroundNumerous studies suggest that the gut microbiota closely linked to cerebrovascular diseases, such as IA and aSAH. Nevertheless, the confirmation of a definitive causal connection between gut microbiota, IA, and aSAH is still pending. The aim of our research is to explore the potential bidirectional causality among them. MethodsThis bidirectional Mendelian Randomization (MR) study used single nucleotide polymorphisms (SNPs) linked to gut microbiota, IA, and aSAH from Genome-Wide Association Studies. The Inverse Variance Weighted (IVW) method was used to explore causality. To assess the robustness of the result, sensitivity analyses were further performed, including weighted-median method, MR-Egger regression, Maximum-likelihood method, MR pleiotropy residual sum and outlier (MR-PRESSO) test and leave-one-out analysis. ResultsIn the IVW method, the family Porphyromonadaceae (OR 0.63; 95% CI 0.47-0.85; P: 0.002) and genus Bilophila (OR 0.66; 95% CI 0.50-0.86; P: 0.002) showed a significant negative association with the risk of IA. Similarly, the genus Bilophila (OR: 0.68; 95% CI: 0.50-0.93; P: 0.017) and genus Ruminococcus1 (OR: 0.48; 95% CI: 0.30-0.78; P: 0.003) were linked to reduced risk of aSAH. The sensitivity analysis yielded similar outcomes in the IVW approach. Through the adoption of reverse MR analysis, a potential correlation between IA and decreased abundance of genus Ruminococcus1 was identified (OR 0.94; 95% CI 0.90-0.99; P 0.024). ConclusionsThis Mendelian randomization analysis investigated the causal associations between gut microbiota, IA, and aSAH risks. The findings expanded current knowledge of the microbiota-gut-brain axis and offered novel perspectives on preventing and managing these conditions.