Exploring Genetic Association Between Gut Microbiota and Thoracic Aortic Aneurysms

Observational studies suggest a link between gut microbiota and thoracic aortic aneurysms (TAA), a blood vessel disease. However, whether this relationship reflects underlying genetic mechanisms remains unclear. GWAS data for TAA, aortic diameter and gut microbiota were obtained from public genome-wide association studies. Mendelian randomization (MR) analysis was performed using methods including MR-Egger, weighted median, weighted mode, and Inverse variance weighted (IVW), with IVW serving as the main analytic approach. Sensitivity analyses included MR-Egger, MR-PRESSO, Cochran’s Q, and leave-one-out techniques, and the false discovery rate (FDR) was applied for multiple testing correction. Finally, network visualisation of MR associations was performed using Python. IVW analysis suggested a nominal genetic association between 21 gut microbiota and TAA. Higher TAA risk showed nominally associations with Family Oxalobacteraceae, Genus unknown genus, and Genus Oxalobacter. Lower TAA risk was nominally linked to Family XI, Class Melainabacteria, Class Deltaproteobacteria, Genus Family XIII UCG001, and Phylum Proteobacteria. Higher ascending aortic diameter (AAD) risk showed nominally associatitons with Genus Lachnospiraceae, Genus Lachnoclostridium, Genus Eggerthella, and Genus Tyzzerella3, while lower risk was nominally associated with Phylum Cyanobacteria, Genus Methanobrevibacter, Genus Lachnospiraceae, and Family Clostridiaceae1. Higher descending aortic diameter (DAD) risk showed nominally associations with Order Enterobacteriales, Family Enterobacteriaceae and Genus Eubacterium rectale, while lower risk was nominally linked to Genus Eubacterium ruminantium. However, none of these associations remained significant after FDR correction (p-FDR > 0.05). The visualised interaction network identified DAD with pro-inflammatory aggregation, AAD with a high degree of complexity and functional heterogeneity, and TAA with both risk and protective factors. Our findings suggest a nominal genetic association between gut microbiota and TAA, indicating exploratory evidence that may inform future research on microbiome-related mechanisms in thoracic aortic aneurysms.