Causal relationships between gut microbiota and Aneurysmal Subarachnoid Hemorrhage: A Bidirectional Mendelian...

Aneurysmal Subarachnoid Hemorrhage (aSAH) poses a significant health burden globally, necessitating a deeper understanding of its etiology and potential preventive strategies. Recent research has suggested a possible link between gut microbiota composition and the risk of vascularity, prompting investigation into this association using Mendelian Randomization (MR) analysis. Here, we aimed to elucidate the causal relationship between gut microbiota composition and aSAH risk utilizing MR analysis.

We employed four distinct MR methodologies, including inverse variance weighted (IVW), MR-Egger, weighted median, and weighted mode, to assess the causal nexus between gut microbiota composition and aSAH risk. Genetic instrumental variables (IVs) associated with gut microbiome composition were selected from a comprehensive multiethnic genome-wide association study (GWAS) involving 18,473 individuals across diverse geographic regions. Sensitivity analyses were conducted to detect potential heterogeneity and pleiotropy.

Our Mendelian Randomization (MR) analyses unveiled a substantial and statistically significant causal relationship between gut microbiota composition and the risk of Aneurysmal Subarachnoid Hemorrhage (aSAH). Employing the Inverse Variance Weighted (IVW) method, we observed negative associations between aSAH and specific taxonomic levels of gut microbiota. Specifically, the IVW approach identified significant associations with one order, Victivallales (P_IVW=0.047, OR: 0.78, 95 % CI: 0.62-0.99), one family, Porphyromonadaceae (P_IVW=0.03, OR: 0.64, 95 % CI: 0.43-0.95), one class, Lentisphaeria (P_IVW=0.047, OR: 0.78, 95 % CI: 0.62-0.99), and three genera: Bilophila (P_IVW=0.02, OR: 0.68, 95 % CI: 0.50-0.93), Fusicatenibacter (P_IVW=0.04, OR: 0.69, 95 % CI: 0.49-0.98), and Ruminococcus1 (P_IVW=0.01, OR: 0.51, 95 % CI: 0.32-0.84). These findings were consistent across various MR methodologies, underscoring the robustness of our results. Sensitivity analyses further validated the stability of our findings, with no evidence of heterogeneity or pleiotropy detected.

Our study provides compelling evidence supporting a causal relationship between gut microbiota composition and the risk of aSAH. These findings underscore the potential therapeutic implications of modulating gut microbiota to prevent and manage aSAH. Further research is warranted to explore the underlying mechanisms and develop targeted interventions aimed at mitigating aSAH risk through gut microbiota modulation.