Causal Associations Between the Gut Microbiome and Aortic Aneurysm: A Mendelian Randomization Study

Abstract

Background: Observational studies have indicated an association between the gut microbiota and the occurrence and progression of aortic aneurysm (AA). However, the causal relationship between the gut microbiota and AA and its subtypes remains unclear. This study used Mendelian randomization (MR) to gain new insights into the relationship between the gut microbiota and AA, including AA subtypes. Methods: We used summary data from a genome-wide association study of gut microbiota to determine genetically predicted microbial taxa. Additionally, we predicted causal relationships between the gut microbiota and AA, including AA subtypes. MR was conducted with two-sample MR with the inverse variance weighting, MR-Egger, weighted median, and weighted mode methods to assess the causal relationships. Heterogeneity and pleiotropy were evaluated with the MR-Egger method, Cochran’s Q test, and the MR-PRESSO Global test. The strength of the causal relationships between exposures and outcomes was assessed with Bonferroni correction. The stability of the MR results was evaluated with leave-one-out analyses. Reverse MR analysis was also performed to examine reverse causality. Results: Through MR analysis, after Bonferroni correction, specific microbial taxa were found to have a causal relationship in AA and its subtypes. Specifically, the phylum Lentisphaerae (OR = 0.82, P = 0.001), class Lentisphaeria (OR = 0.81, P = 0.0028), and family Bifidobacteriaceae (OR = 0.79, P < 0.001) were negatively associated with AA risk, whereas the genus Family XIII UCG001 (OR = 1.33, P < 0.001) was positively associated with AA risk. Regarding subtypes, elevated levels of the genus Bilophila (OR = 1.36, P < 0.001) were closely associated with abdominal aortic aneurysm (AAA) occurrence. Lower levels of the family Bifidobacteriaceae (OR = 0.71, P < 0.001) and phylum Lentisphaerae (OR = 0.81, P = 0.0025), and higher levels of the genus Ruminococcaceae UCG014 (OR = 1.30, P < 0.001) exhibited strong causal relationships with thoracic aortic aneurysm (TAA). Conclusion: Our study suggests that specific components of the gut microbiota have causal effects, either beneficial or detrimental, on AA risk, thus providing potentially valuable biomarkers for early diagnosis and potential therapeutic targets.