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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.<\/jats:p>\n                  <jats:p>\n                    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\n                    <jats:italic>Firmicutes<\/jats:italic>\n                    -enriched microbiota and androgenic modulation, which might promote calcification and inflammatory signaling in the aortic valve.\n                  <\/jats:p>\n                  <jats:p>This review integrates current knowledge on sex-related differences in AS, spanning clinical patterns, valvular remodeling, cellular and molecular signaling, and gut\u2013heart interactions, to propose a hypothesis-driven framework on how gut microbiota may contribute to sex-specific differences in AS.<\/jats:p>","DOI":"10.1186\/s13293-026-00932-7","type":"journal-article","created":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T12:33:53Z","timestamp":1780058033000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The potential role of sex related differences of the microbiome and its impact on calcific aortic stenosis: a narrative review"],"prefix":"10.1186","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-2646-7993","authenticated-orcid":false,"given":"Sarah","family":"Atighetchi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8721-4068","authenticated-orcid":false,"given":"Thomas","family":"Pilgrim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1888-9226","authenticated-orcid":false,"given":"Yilmaz","family":"Bahtiyar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2273-1528","authenticated-orcid":false,"given":"Gaspard","family":"Suc","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4150-290X","authenticated-orcid":false,"given":"Marina","family":"Urena-Alcazar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9307-3396","authenticated-orcid":false,"given":"Yvonne","family":"D\u00f6ring","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2575-7929","authenticated-orcid":false,"given":"Caroline","family":"Chong-Nguyen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,29]]},"reference":[{"issue":"7","key":"932_CR1","doi-asserted-by":"publisher","first-page":"561","DOI":"10.1093\/eurheartj\/ehab395","volume":"43","author":"A Vahanian","year":"2022","unstructured":"Vahanian A, Beyersdorf F, Praz F, Milojevic M, Baldus S, Bauersachs J, Capodanno D, Conradi L, De Bonis M, De Paulis R, Delgado V, Freemantle N, Gilard M, Haugaa KH, Jeppsson A, J\u00fcni P, Pierard L, Prendergast BD, S\u00e1daba JR, ESC National Cardiac Societies. 2021 ESC\/EACTS Guidelines for the management of valvular heart disease: Developed by the Task Force for the management of valvular heart disease of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS). 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