Aortic stenosis is a heart valve disease and, in this context, was studied as the outcome in a multi-omics Mendelian randomization framework using mendelian randomization to test causal associations. The analysis linked AS to multiple biological layers, including gut microbiome, blood metabolites, immune cell phenotypes, and circulating inflammatory proteins, suggesting a complex inflammatory-metabolic contribution to disease risk. Key findings included 7 gut microbiota, 80 metabolites, 29 immune cell phenotypes, and 6 circulating inflammatory proteins that were causally associated with AS. Pathway analysis also implicated valine, leucine, and isoleucine biosynthesis, and co-localization supported a significant correlation between 1-stearoyl-2-acryloyl-GPE and AS. Overall, the literature points to AS as a multifactorial valvular disorder with measurable causal signals across microbiome, metabolome, and immune/inflammatory profiles.
Multi-omics and causal inference
- A 2026 Medicine study (PMID:41961656) used multi-omics Mendelian randomization to investigate causal relationships between gut microbiome, plasma metabolites, inflammation, and aortic stenosis. (PMID:41961656)
- The study identified AS as an outcome disease with causal associations spanning 7 gut microbiota, 80 metabolites, 29 immune cell phenotypes, and 6 circulating inflammatory proteins. (PMID:41961656)
- Blood metabolites were systematically analyzed, and 80 metabolites were reported as causally associated with AS. (PMID:41961656)
- Circulating inflammatory proteins were also assessed, with 6 proteins showing causal association with AS. (PMID:41961656)
Microbiome, immune, and metabolic associations
- Gut microbiota analysis found 7 taxa causally associated with AS, supporting a microbiome link to valvular disease. (PMID:41961656)
- Immune profiling identified 29 immune cell phenotypes causally associated with AS, indicating immune-state involvement in disease susceptibility. (PMID:41961656)
- Metabolic pathway analysis implicated valine, leucine, and isoleucine biosynthesis as an AS-associated pathway. (PMID:41961656)
- Co-localization analysis showed a significant correlation between 1-stearoyl-2-acryloyl-GPE levels and AS. (PMID:41961656)