Sex-related differences in the gut microbiome and its metabolites may contribute to the distinct pathophysiological patterns of aortic stenosis observed between men and women.
This review highlights the potential role of gut microbiota and its metabolites in driving sex-specific differences in the pathophysiology and clinical presentation of aortic stenosis.
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.Aortic stenosis (AS) affects men and women differently. Women are usually older when the disease is diagnosed, often feel more symptoms, and tend to have a form of the disease with less blood flow and more stiffening of the heart muscle. Their heart valves are more fibrotic (scar-like). Men, on the other hand, more often develop heavily calcified (hardened) valves and a different pattern of heart enlargement.These differences are not just about heart structure or blood flow — they may also be linked to deeper biological processes, including the gut microbiome (the bacteria living in our intestines).Recent research suggests that gut bacteria and the substances they produce can influence how AS develops, and this may differ between men and women. Women tend to have a more diverse and protective gut microbiome, partly influenced by hormones like estrogen and diet. This may lead to lower levels of harmful substances and more fibrotic (less calcified) valve changes. Men, in contrast, often have higher levels of certain metabolites (such as TMAO and indoxyl sulfate) that have been shown in the literature to be linked to inflammation and valve calcification.This review brings together current knowledge on how sex differences, heart changes, biological pathways, and the gut microbiome interact in AS to propose a hypothesis-driven framework linking gut microbiota and its metabolites to sex-specific differences in AS pathophysiology.
Atighetchi et al. (Fri,) conducted a review in Aortic stenosis. Gut microbiome and its metabolites was evaluated. Sex-related differences in the gut microbiome and its metabolites may contribute to the distinct pathophysiological patterns of aortic stenosis observed between men and women.