Causal Associations Between Gut Microbiota and Cerebrovascular Diseases

Numerous studies suggest that the gut microbiota closely linked to cerebrovascular diseases, such as Intracranial aneurysm (IA) and aneurysmal subarachnoid hemorrhage (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.

This bidirectional Mendelian Randomization (MR) study used single nucleotide polymorphisms 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 test and leave-one-out analysis.

In the IVW method, the family Porphyromonadaceae (odds ratio [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).

This MR 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.