Aneurysms, including intracerebral aneurysm (IA), thoracic aortic aneurysm (TAA), abdominal aortic aneurysm (AAA), and aortic aneurysm (AA), pose significant health risks and their etiology involves complex interplays of genetic, environmental, and microbial factors. Recent studies have implicated the gut microbiome (GM) in the pathogenesis of aneurysms, but the causal association remains unclear. Researchers in this study present a two-sample Mendelian randomization (MR) analysis investigating the causal effect of specific gut microbiomes on aneurysm risk.
Methods:
- Two-sample MR was conducted using single nucleotide polymorphisms (SNPs) as instrumental variables to assess causal associations between gut microbiomes and aneurysms.
- Instrumental variables were selected based on locus-wide significance level criteria.
- Primary analysis utilized the inverse-variance weighted (IVW) test, with sensitivity analysis conducted using MR-Egger, weighted median, weighted mode, and MR Pleiotropy Residual Sum and Outlier (MR-PRESSO) methods.
- False discovery rate (FDR) adjustment was applied for multiple comparisons, with significance set at p < 0.05 and q < 0.1.
- Reverse MR analysis was performed to exclude reverse causality.
Key Findings:
- Protective Gut Microbiomes Against AAA:
- Phylum ๐๐ช๐ณ๐ฎ๐ช๐ค๐ถ๐ต๐ฆ๐ด, class ๐๐ฆ๐ฏ๐ต๐ช๐ด๐ฑ๐ฉ๐ข๐ฆ๐ณ๐ช๐ข, and order ๐๐ช๐ค๐ต๐ช๐ท๐ข๐ญ๐ญ๐ข๐ญ๐ฆ exhibited a causal protective effect against AAA.
- Decreased abundance of these gut microbiomes was associated with higher risk of AAA.
2. Specific Gut Microbiomes Associated with Aneurysms:
- Class ๐๐ฆ๐ณ๐ณ๐ถ๐ค๐ฐ๐ฎ๐ช๐ค๐ณ๐ฐ๐ฃ๐ช๐ข, class ๐๐ฆ๐ญ๐ต๐ข๐ฑ๐ณ๐ฐ๐ต๐ฆ๐ฐ๐ฃ๐ข๐ค๐ต๐ฆ๐ณ๐ช๐ข, order ๐๐ฆ๐ณ๐ณ๐ถ๐ค๐ฐ๐ฎ๐ช๐ค๐ณ๐ฐ๐ฃ๐ช๐ข๐ญ๐ฆ, family ๐๐ฆ๐ณ๐ณ๐ถ๐ค๐ฐ๐ฎ๐ช๐ค๐ณ๐ฐ๐ฃ๐ช๐ข๐ค๐ฆ๐ข, genus ๐๐ถ๐ฃ๐ข๐ค๐ต๐ฆ๐ณ๐ช๐ถ๐ฎ ๐ณ๐ฆ๐ค๐ต๐ข๐ญ๐ฆ group, genus ๐๐ฌ๐ฌ๐ฆ๐ณ๐ฎ๐ข๐ฏ๐ด๐ช๐ข, and genus ๐๐ญ๐ฐ๐ด๐ต๐ณ๐ช๐ฅ๐ช๐ถ๐ฎ ๐ช๐ฏ๐ฏ๐ฐ๐ค๐ถ๐ถ๐ฎ group were negatively associated with various types of aneurysms.
- Class ๐๐ฆ๐จ๐ข๐ต๐ช๐ท๐ช๐ค๐ถ๐ต๐ฆ๐ด, order ๐๐ฆ๐ญ๐ฆ๐ฏ๐ฐ๐ฎ๐ฐ๐ฏ๐ข๐ฅ๐ข๐ญ๐ฆ๐ด, and genus ๐๐ฐ๐ด๐ฆ๐ฃ๐ถ๐ณ๐ช๐ข showed positive causal associations with different types of aneurysms.
3. Sensitivity Analysis and Robustness:
- Sensitivity analysis validated the robustness of MR results.
- No evidence of reverse causality was found in the analysis.
Biological Insights:
- Gut microbiomes, particularly ๐๐ช๐ณ๐ฎ๐ช๐ค๐ถ๐ต๐ฆ๐ด, ๐๐ฆ๐ฏ๐ต๐ช๐ด๐ฑ๐ฉ๐ข๐ฆ๐ณ๐ช๐ข, ๐ข๐ฏ๐ฅ ๐๐ช๐ค๐ต๐ช๐ท๐ข๐ญ๐ญ๐ข๐ญ๐ฆ๐ด, play a crucial role in modulating aneurysm risk.
- Butyrate production by ๐๐ช๐ณ๐ฎ๐ช๐ค๐ถ๐ต๐ฆ๐ด may contribute to anti-inflammatory and antioxidant effects, potentially mitigating atherosclerosis and AAA progression.
- Phylum ๐๐ฆ๐ฏ๐ต๐ช๐ด๐ฑ๐ฉ๐ข๐ฆ๐ณ๐ช๐ข, previously associated with Parkinson’s disease, demonstrated a protective effect against aneurysms, suggesting a novel therapeutic target.
- Additional gut microbiomes like ๐๐ฌ๐ฌ๐ฆ๐ณ๐ฎ๐ข๐ฏ๐ด๐ช๐ข ๐ข๐ฏ๐ฅ ๐๐ถ๐ฃ๐ข๐ค๐ต๐ฆ๐ณ๐ช๐ถ๐ฎ ๐ณ๐ฆ๐ค๐ต๐ข๐ญ๐ฆ group may also influence aneurysm formation and progression through their metabolic and immunomodulatory effects.
Strengths and Limitations:
- Strengths include the robust MR methodology, stringent quality control measures, and sensitivity analysis.
- Limitations include the generalizability of findings to other ethnic populations, the need for further exploration of gut microbiomes at finer taxonomic levels, and potential confounding factors not addressed in MR analysis.
This study highlights the emerging role of the gut microbiome as a modulator of aneurysm risk and provides insights into potential preventive and therapeutic strategies for these life-threatening conditions.
Link to the study : https://tinyurl.com/36cexber
