Causal Associations Between Gut Microbiota and Cerebrovascular Diseases

Abstract

Background: 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.

Methods: 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.

Results: 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).

Conclusions: 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.

Keywords: Aneurysmal subarachnoid hemorrhage; Genome-wide association studies; Gut microbiota; Intracranial aneurysm; Mendelian randomization; Stroke.