Gut Microbiota, Metabolites, Circulating Cytokines and Growth Factors, Plasma Proteins, and Risk of Intracranial Aneurysms: A Two-Sample Mendelian Randomization Study

Background: Increasing evidence implicates the gut microbiota, metabolites, circulating cytokines and growth factors, and plasma proteins as potential susceptibility factors for intracranial aneurysm (IA). However, due to their complexity, the causal relationship between these factors and IA remains unclear. Our goal was to determine whether these factors are causally associated with IA, UIA, and SAH and provide suggestions for the prevention and treatment of these cerebrovascular diseases.

Methods: Utilizing data from genome-wide association studies (GWAS), we conducted a large-scale Mendelian randomization (MR) analysis between these factors and diseases using five different models (Wald ratio, IVW, MR-Egger, weighted median, and MRPRESSO). Several sensitivity analyses were also applied to ensure the robustness of the results.

Results: Our MR analysis revealed several significant causal relationships between 18 gut microbiota taxa (genus.Bilophila-SAH, beta[95%CI] = −1.08[−1.61 ~ −0.54]), 55 blood metabolites (7-alpha-hydroxy-3-oxo-4-cholestenoate-IA, beta[95%CI] = −2.78[−4.47 ~ −1.08]), 2 cytokines (IL-6-UIA, beta[95%CI] = 0.73[0.34 ~ 1.39]), 45 plasma proteins (RELT-UIA, beta[95%CI] = −0.8[−1.22 ~ −0.38]), and IA, UIA, and SAH. Many of these were reported for the first time.

Conclusions: In conclusion, our study provides reference of the potential causal effects of gut microbiota, blood metabolites, cytokines, and plasma proteins on IA, UIA, and SAH. These findings may contribute to a better understanding of the pathogenesis and potential therapeutic targets for these cerebrovascular diseases.