Genetic Causal Association Between the Gut Microbiome and Intracranial Aneurysm and Subarachnoid Hemorrhage: A Two-Sample Mendelian Randomization Study

Mei He; Wenjing Wang; Qiang He; Heling Dai; Jinming Han; Wenyao Cui

doi:10.1007/s40120-023-00525-1

Genetic Causal Association Between the Gut Microbiome and Intracranial Aneurysm and Subarachnoid Hemorrhage: A Two-Sample Mendelian Randomization Study

Neurol Ther. 2023 Oct;12(5):1695-1707. doi: 10.1007/s40120-023-00525-1. Epub 2023 Jul 13.

Authors

Mei He¹, Wenjing Wang², Qiang He³, Heling Dai³, Jinming Han⁴, Wenyao Cui⁵

Affiliations

¹ Department of Anesthesiology and Operating Room, West China Hospital, Sichuan University, No. 37 Guo Xue Xiang, Chengdu, Sichuan, China.
² Department of Pharmacy, Institute of Metabolic Diseases and Pharmacotherapy, West China Hospital, Sichuan University, Chengdu, China.
³ Department of Neurosurgery, West China Hospital, Sichuan University, 37 Guoxue Lane, Wuhou District, Chengdu, Sichuan, China.
⁴ Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China. hanjinming1202@126.com.
⁵ Department of Neurosurgery, West China Hospital, Sichuan University, 37 Guoxue Lane, Wuhou District, Chengdu, Sichuan, China. cuiwenyao@wchscu.cn.

Abstract

Introduction: The causal association between the gut microbiome and the risk of intracranial aneurysm (IA), subarachnoid hemorrhage (SAH), and unruptured aneurysm (uIA) is unclear.

Methods: The single nucleotide polymorphisms concerning gut microbiome were retrieved from the gene-wide association study (GWAS) of the MiBioGen consortium. The summary-level datasets of IA and SAH were obtained from the GWAS meta-analysis of the International Stroke Genetics Consortium (ISGC). Inverse variance weighting (IVW) was utilized as the primary method, complemented with sensitivity analyses for pleiotropy and increasing robustness.

Results: Five, seven, and six bacterial traits were found to have a causal effect on IA, SAH, and uIA, respectively (IVW, all P < 0.05). Family.Porphyromonadaceae and genus.Bilophila were common protective bacterial features for both SAH and uIA. The heterogeneity and pleiotropy analyses confirmed the robustness of IVW results.

Conclusion: Our study demonstrates that gut microbiomes may exert therapeutic effects on IA, uIA, and SAH, providing clinical implications for the development of novel biomarkers and therapeutic targets.

Keywords: Causal association; Gut microbiome; Intracranial aneurysm; Mendelian randomization; Subarachnoid hemorrhage.

Grants and funding

81701292/81701292