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<p>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.</p><p>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 <i>Firmicutes</i>-enriched microbiota and androgenic modulation, which might promote calcification and inflammatory signaling in the aortic valve.</p><p>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.</p>

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The potential role of sex related differences of the microbiome and its impact on calcific aortic stenosis: a narrative review

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年5月29日

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  • Sarah Atighetchi,
  • Thomas Pilgrim,
  • Yilmaz Bahtiyar,
  • Gaspard Suc,
  • Marina Urena-Alcazar,
  • Yvonne Döring,
  • Caroline Chong-Nguyen

摘要

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.