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The gut microbiota refers to the diverse microbial ecosystem inhabiting the gastrointestinal tract, including bacteria, fungi, viruses, and other microorganisms. This community exhibits considerable variability in both population density and taxonomic composition, with current estimates indicating approximately 1013\u20131014 microorganisms residing in the human gut. Recent studies suggest that metabolites produced by the gut microbiota may influence the pathogenesis of VC through the gut\u2013vascular axis. This review consolidates current findings on the molecular mechanisms driving VC and examines the potential contribution of gut microbiota dysbiosis to vascular pathology. Particular attention is given to the functional roles of microbial metabolites such as short-chain fatty acids (SCFAs), trimethylamine N-oxide (TMAO), lipopolysaccharide (LPS), uremic toxins, secondary bile acids, and vitamin K in modulating calcific processes. In addition, current limitations in the existing literature are outlined, and potential therapeutic approaches, including probiotic use, prebiotic interventions, and targeted dietary strategies, are discussed in the context of their relevance for future clinical management of VC.<\/jats:p>","DOI":"10.3390\/ijms27031364","type":"journal-article","created":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T16:08:17Z","timestamp":1769702897000},"page":"1364","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["The Role and Mechanism of Gut Microbiota and Metabolites in Vascular Calcification"],"prefix":"10.3390","volume":"27","author":[{"given":"Xing-Yu","family":"Cao","sequence":"first","affiliation":[{"name":"MOE Medical Basic Research Innovation Center for Gut Microbiota and Chronic Diseases, School of Medicine, Jiangnan University, Wuxi 214122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ao-Yuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"MOE Medical Basic Research Innovation Center for Gut Microbiota and Chronic Diseases, School of Medicine, Jiangnan University, Wuxi 214122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke-Feng","family":"Li","sequence":"additional","affiliation":[{"name":"MOE Medical Basic Research Innovation Center for Gut Microbiota and Chronic Diseases, School of Medicine, Jiangnan University, Wuxi 214122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Wen","family":"Bie","sequence":"additional","affiliation":[{"name":"MOE Medical Basic Research Innovation Center for Gut Microbiota and Chronic Diseases, School of Medicine, Jiangnan University, Wuxi 214122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gui-Wen","family":"Xu","sequence":"additional","affiliation":[{"name":"MOE Medical Basic Research Innovation Center for Gut Microbiota and Chronic Diseases, School of Medicine, Jiangnan University, Wuxi 214122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chu-Yue","family":"Zhou","sequence":"additional","affiliation":[{"name":"MOE Medical Basic Research Innovation Center for Gut Microbiota and Chronic Diseases, School of Medicine, Jiangnan University, Wuxi 214122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Yue","family":"Ma","sequence":"additional","affiliation":[{"name":"MOE Medical Basic Research Innovation Center for Gut Microbiota and Chronic Diseases, School of Medicine, Jiangnan University, Wuxi 214122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"You-Yi","family":"Zhuang","sequence":"additional","affiliation":[{"name":"MOE Medical Basic Research Innovation Center for Gut Microbiota and Chronic Diseases, School of Medicine, Jiangnan University, Wuxi 214122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hai-Jian","family":"Sun","sequence":"additional","affiliation":[{"name":"MOE Medical Basic Research Innovation Center for Gut Microbiota and Chronic Diseases, School of Medicine, Jiangnan University, Wuxi 214122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4735-5648","authenticated-orcid":false,"given":"Xue-Xue","family":"Zhu","sequence":"additional","affiliation":[{"name":"MOE Medical Basic Research Innovation Center for Gut Microbiota and Chronic Diseases, School of Medicine, Jiangnan University, Wuxi 214122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1016\/j.jacc.2021.06.049","article-title":"Medial Arterial Calcification: JACC State-of-the-Art Review","volume":"78","author":"Lanzer","year":"2021","journal-title":"J. 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