Exploring the Relationship Between Gut Microbiota and Aortic Stenosis: Role of Inflammatory Proteins, Blood Metabolites, and Immune Cells.

Background: Aortic stenosis is the most prevalent valvular heart disease in high-income population, and there are currently no medical therapies to slow the disease progression. Given that gut microbiota influences the immune system, lipid metabolism, and inflammation, there may be a potential link between gut microbiota and AS. Aims: We aimed to examine the causal effects of gut microbiota on AS and to investigate the mediating roles of inflammatory proteins, blood metabolites, and immune cells. Methods: Bidirectional Mendelian randomization analysis was performed to assess the causal relationships between gut microbiota, inflammatory proteins, blood metabolites, immune cells, and AS. Two-step Mendelian randomization was utilized to explore direct and indirect effects. The data were derived from genome-wide association study summary statistics available in public databases. Results: The study identified nine gut microbial features (six microbial taxa and three pathways), four inflammatory proteins, 91 blood metabolites, and four immune cell traits associated with AS. However, no significant mediating roles were found for inflammatory proteins, blood metabolites, and immune cells in the causal pathway between gut microbiota and AS. Conclusion: This study revealed novel causal associations between gut microbial features, inflammatory proteins, blood metabolites, and immune cell traits with AS. These findings offer new insights into the pathophysiology of AS and provide potential targets for therapeutic approaches.