Association of gut microbiome with risk of intracranial aneurysm: a mendelian randomization study

Abstract

Objective To investigate the potential causal link between genetic variants associated with gut microbiome and risk of intracranial aneurysm (IA) using two-sample mendelian randomization (MR). Methods We performed two sets of MR analyses. At first, we selected the genome-wide statistical significant(P < 5 × 10–8) single nucleotide polymorphisms (SNPs) as instrumental variables (IVs). Then, we selected the locus-wide significant (P < 1 × 10–5) SNPs as IVs for the other set of analyses to obtain more comprehensive conclusions. Gut microbiome genetic association estimates were derived from a genome-wide association study (GWAS) of 18,473 individuals. Summary-level statistics for IA were obtained from 79,429 individuals, which included 7,495 cases and 71,934 controls. Results On the basis of locus-wide significance level, inverse variance weighted(IVW) showed that Clostridia [(odds ratio (OR): 2.60; 95% confidence interval (CI): 1.00—6.72, P = 0.049)], Adlercreutzia (OR: 1.81; 95% CI: 1.10—2.99, P = 0.021) and Victivallis (OR: 1.38; 95% CI: 1.01—1.88, P = 0.044) were positively related with the risk of unruptured intracranial aneurysm(UIA); Weighted median results of MR showed Oscillospira (OR: 0.37; 95% CI: 0.17—0.84, P = 0.018) was negatively with the risk of UIA and Sutterella (OR: 1.84; 95% CI: 1.04—3.23, P = 0.035) was positively related with the risk of UIA; MR-Egger method analysis indicated that Paraprevotella (OR: 0.32; 95% CI: 0.13—0.80, P = 0.035) was negatively with the risk of UIA and Rhodospirillaceae (OR: 13.39; 95% CI: 1.44—124.47, P = 0.048) was positively related with the risk of UIA. The results suggest that Streptococcus (OR: 5.19; 95% CI: 1.25—21.56; P = 0.024) and Peptostreptococcaceae (OR: 4.92; 95% CI: 1.32—18.32; P = 0.018) may increase the risk of UIA according to genome-wide statistical significance thresholds. Conclusion This MR analysis indicates that there exists a beneficial or detrimental causal effect of gut microbiota composition on IAs.

Gut microbiome in intracranial aneurysm growth, subarachnoid hemorrhage, and cerebral vasospasm: a systematic review with a narrative synthesis

“…Ma et al performed a Mendelian randomization study on a dataset from a genome-wide association study and detected one bacterial family and one genus in gut microbiota that reached the genome-wide statistically significant threshold. Peptostreptococcaceae (OR: 4.92; 95% CI: 1.32–18.32; P = 0.018) and Streptococcus (OR: 5.19; 95% CI: 1.25–21.56; P = 0.024) could increase the risk of IA (Ma et al, 2023 ). Streptococcus is known for mediating immune response via proinflammatory cytokines (interleukin-1 and interleukin-6), whereas Peptostreptococcaceae is involved in atherosclerosis and might promote the growth of aneurysms.…”

“…Other bacteria that were linked to IA but did not reach GWAS significance were Adlercreutzia, Clostridia, Rhodospirillaceae, Sutterella, Victivallis, Oscillospira , and Paraprevotella . To confirm that any of these microbiota representatives might potentially serve as kind of a microbiological marker of the disease, observational studies are needed (Ma et al, 2023 ). Qin et al performed a similar study utilizing the Mendelian randomization technique.…”

The Role of Gut and Oral Microbiota in the Formation and Rupture of Intracranial Aneurysms: A Literature Review

“…Another Mendelian randomization study by Ma et al [ 68 ] indicated bacteria with beneficial and detrimental effects on IAs as well ( Table 1 ). However, both studies did not reflect other individual risk factors.…”