Key result
Sex-specific gut microbiota and TMAO differences may contribute to distinct calcific aortic stenosis patterns.
Why the study?
Aortic stenosis exhibits distinct sex-related differences in clinical manifestation and pathophysiology, and gut microbiota composition and its metabolites may play an emerging sex-specific role in its pathogenesis.
This review proposes a hypothesis-driven framework suggesting that sex-specific differences in gut microbiota and its metabolites contribute to the distinct pathophysiological patterns of aortic stenosis seen in men and women.
Sex-specific microbiota profiles may influence aortic stenosis progression; leaves open whether microbiome-targeted therapies warrant sex-stratified trials.
Aortic stenosis (AS) presents with distinct sex-related differences in clinical manifestation, pathophysiology, and response to treatment. Women typically present at an older age, with greater frailty, more pronounced symptoms, and paradoxical low-flow AS, often associated with concentric left ventricular remodeling and fibrotic valve changes. In contrast, men show a predominance of calcific AS, eccentric remodeling, and more extensive aortic valve calcification. These differences are not solely anatomical or hemodynamic; they extend to molecular pathways and emerging contributors such as the gut microbiota. Recent evidence suggests that gut microbiota composition and its metabolites, particularly trimethylamine-N-oxide (TMAO) and indoxyl sulfate (IS), play a sex-specific role in AS pathogenesis. Women generally exhibit a more diverse and cardioprotective microbiota profile, shaped by estrogen and dietary habits, that might explain lower levels of pro-calcific metabolites and a fibrotic valve phenotype. Conversely, men tend to have higher TMAO and IS levels, driven by a Firmicutes -enriched microbiota and androgenic modulation, which might promote calcification and inflammatory signaling in the aortic valve. This review integrates current knowledge on sex-related differences in AS, spanning clinical patterns, valvular remodeling, cellular and molecular signaling, and gut–heart interactions, to propose a hypothesis-driven framework on how gut microbiota may contribute to sex-specific differences in AS.
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Atighetchi et al. (2026) conducted a review in Calcific aortic stenosis. Gut microbiota and metabolites vs. Sex differences (Men vs Women) was evaluated. Sex-specific differences in gut microbiota composition and metabolites, particularly TMAO, may contribute to the distinct pathophysiological patterns of calcific aortic stenosis observed in men and women.
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