Gut Microbiota Influences Aortic Dissection Risk via Cortisol: A Mendelian Randomization Study

The association between the gut microbiota and aortic dissection(AD) progression remains to be fully characterized, and current evidence regarding the influence of cortisol on this relationship remains inconclusive. The aim of this study was to determine whether cortisol levels contribute to this association.

A two-sample Mendelian Randomization (MR) approach was implemented, incorporating gut microbiota summary statistics derived from a large-scale genome-wide association meta-analysis (n=18,340) performed by the MiBioGen consortium. Additionally, summary-level data on aortic dissection were obtained from the FinnGen Consortium R10 release, which included 967 cases and 381,977 controls. To investigate causal relationships, the study implemented inverse-variance weighting, a weighted model, a weighted median, MR-Egger, and MRPRESSO. Mediated MR analyses were performed on bacteria identified as causally associated with aortic dissection, along with intermediate metabolites derived from 1,400 blood metabolites, and the metabolites that mediated the relationship between them were identified. The study employed Cochran's Q test to examine heterogeneity in the genetic instruments.

Seven gut microbiota species with elevated abundance potentially exerts a protective or negative effect on aortic dissection. In particular, the Ruminococcus gnavus group may have a deleterious effect on aortic dissection via changes in cortisol levels.

This study offers novel insights into the involvement of gut microbiota in the prevention of aortic dissection and the complex relationship between them. Additionally, it underscores the significance of randomized controlled trials in determining the association linking gut microbiota with aortic dissection risks.