Department of Cerebrovascular Surgery, Affiliated Hospital of Guangdong Medical University, Zhanjiang, PR China.
Department of Cerebrovascular Surgery, Affiliated Hospital of Guangdong Medical University, Zhanjiang, PR China.
J Stroke Cerebrovasc Dis. 2024 Dec;33(12):108030. doi: 10.1016/j.jstrokecerebrovasdis.2024.108030. Epub 2024 Sep 29.
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=0.047, OR: 0.78, 95 % CI: 0.62-0.99), one family, Porphyromonadaceae (P=0.03, OR: 0.64, 95 % CI: 0.43-0.95), one class, Lentisphaeria (P=0.047, OR: 0.78, 95 % CI: 0.62-0.99), and three genera: Bilophila (P=0.02, OR: 0.68, 95 % CI: 0.50-0.93), Fusicatenibacter (P=0.04, OR: 0.69, 95 % CI: 0.49-0.98), and Ruminococcus1 (P=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.
蛛网膜下腔出血（aSAH）在全球范围内造成了巨大的健康负担，因此需要深入了解其病因和潜在的预防策略。最近的研究表明，肠道微生物群落组成与血管风险之间可能存在关联，这促使我们使用孟德尔随机化（MR）分析来研究这种关联。在这里，我们旨在利用 MR 分析阐明肠道微生物群落组成与 aSAH 风险之间的因果关系。
我们使用了四种不同的 MR 方法，包括逆方差加权（IVW）、MR-Egger、加权中位数和加权模式，来评估肠道微生物群落组成与 aSAH 风险之间的因果关系。与肠道微生物组组成相关的遗传工具变量（IVs）是从一项涉及来自不同地理区域的 18473 个人的多民族全基因组关联研究（GWAS）中选择的。进行了敏感性分析以检测潜在的异质性和多效性。
我们的孟德尔随机化（MR）分析揭示了肠道微生物群落组成与蛛网膜下腔出血（aSAH）风险之间存在显著且具有统计学意义的因果关系。使用逆方差加权（IVW）方法，我们观察到肠道微生物群落组成与 aSAH 之间存在负相关。具体来说，IVW 方法确定了与一个目（Victivallales）、一个科（Porphyromonadaceae）、一个纲（Lentisphaeria）和三个属（Bilophila、Fusicatenibacter 和 Ruminococcus1）之间存在显著关联：Victivallales（P=0.047，OR：0.78，95%CI：0.62-0.99）、Porphyromonadaceae（P=0.03，OR：0.64，95%CI：0.43-0.95）、Lentisphaeria（P=0.047，OR：0.78，95%CI：0.62-0.99）和三个属：Bilophila（P=0.02，OR：0.68，95%CI：0.50-0.93）、Fusicatenibacter（P=0.04，OR：0.69，95%CI：0.49-0.98）和 Ruminococcus1（P=0.01，OR：0.51，95%CI：0.32-0.84）。这些发现与各种 MR 方法一致，突显了我们结果的稳健性。敏感性分析进一步验证了我们发现的稳定性，没有发现异质性或多效性的证据。
我们的研究提供了有力的证据，支持肠道微生物群落组成与 aSAH 风险之间存在因果关系。这些发现强调了通过调节肠道微生物群来预防和管理 aSAH 的潜在治疗意义。需要进一步研究来探索潜在的机制，并开发靶向干预措施，通过调节肠道微生物群来降低 aSAH 的风险。
