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

Area of Science:

• Genetics
• Microbiology
• Cardiovascular Disease

Background:

• The link between gut microbiota and aortic dissection (AD) progression is not fully understood.
• The role of cortisol in this association is inconclusive.
• This study aimed to clarify cortisol's contribution to the gut microbiota-AD relationship.

Purpose of the Study:

• To investigate the causal relationship between gut microbiota and aortic dissection.
• To determine if cortisol levels mediate the association between gut microbiota and aortic dissection.
• To identify specific gut bacteria and metabolites involved in aortic dissection risk.

Main Methods:

• Two-sample Mendelian Randomization (MR) using large-scale genome-wide association meta-analysis data for gut microbiota (n=18,340) and aortic dissection (967 cases, 381,977 controls).
• Utilized inverse-variance weighting, weighted median, MR-Egger, and MRPRESSO for causal inference.
• Performed mediated MR analyses incorporating blood metabolites to identify mediating pathways.

Main Results:

• Seven gut microbial species showed a potential protective or negative effect on aortic dissection.
• The Ruminococcus gnavus group was identified as potentially deleterious, possibly acting through cortisol level alterations.
• Mediated analyses identified specific metabolites linking gut bacteria to aortic dissection.

Conclusions:

• Gut microbiota plays a role in aortic dissection development and prevention.
• Cortisol may mediate the effect of certain gut bacteria, like Ruminococcus gnavus, on aortic dissection.
• Randomized controlled trials are crucial for validating the link between gut microbiota and aortic dissection risk.