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

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

Mei He  1 , Wenjing Wang  2 , Qiang He  3 , Heling Dai  3 , Jinming Han  4 , Wenyao Cui  5
Affiliations

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

Mei He et al. Neurol Ther. 2023 Oct.

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.

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Conflict of interest statement

All authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Fig. 1
Fig. 1
Causal effect of the gut microbiome on IA, uIA, and SAH based on MR analyses. From outside to inside, the P values of IVW, MR Egger, WMe, WMo, and SM are represented, respectively. The GM taxa name represented by each ID can be found in Table S1. a MR results of IA. b MR results of SAH. c MR results of uIA. IVW inverse variance weighted, WMe weighted median, WMo weighted mode, SM simple mode
Fig. 2
Fig. 2
Causal effect estimates of the gut microbiome on IA. IA intracranial aneurysms, OR odds ratio, CI confidence interval, IVW inverse variance weighted method, RAPS robust adjusted profile score, MR Mendelian randomization
Fig. 3
Fig. 3
Causal effect estimates of the gut microbiome on SAH. SAH subarachnoid hemorrhage, OR odds ratio, CI confidence interval, IVW inverse variance weighted method, RAPS robust adjusted profile score, MR Mendelian randomization
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