Progressive and concordant alterations in transcriptional and gut microbiota across aortic valve calcification severity.

UNLABELLED: Calcific aortic valve disease (CAVD) is a common disorder associated with substantial morbidity and mortality. Although the gut microbiome has complex associations with cardiovascular disease, its variation across the calcification spectrum in CAVD remains poorly defined. We profiled aortic-valve transcriptomes from 31 patients spanning graded calcification and paired these with matched stool microbiome profiles. We identified subtle yet widespread transcriptional changes in mild CAVD (m-CAVD), consistent with a progressive relationship between calcification burden and gene-expression remodeling. At the community level, the gut microbiome in m-CAVD exhibited an intermediate configuration between non- and higher-calcification profiles, suggesting an early shift in the gut ecosystem along the disease continuum. At the genus level, we identified 11 taxa associated with stage; notably, Anaerococcus increased with calcification burden, whereas Rheinheimera declined across stages. These results refine the pathophysiology landscape of CAVD by connecting stage-dependent valvular transcriptional changes with coordinated shifts in the gut microbiome and indicate that early, microbiome-targeted interventions may be promising.

IMPORTANCE: Calcific aortic valve disease is a common valvular heart disease. Due to the difficulty in sampling arterial calcified tissues, research on the interaction between their gene expression and the gut has been limited. In this study, by analyzing the transcriptional profiles of calcified aortic valve tissues from patients with different levels of calcification and the characteristics of their corresponding gut microbiota, we identified consistent features between lesion gene expression and gut microbiota variation. This provides important evidence for the association between the gut microbiota and disease development stages, offering a new perspective for understanding disease progression and early intervention.