{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T16:05:11Z","timestamp":1790352311160,"version":"4.1.0"},"reference-count":193,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2024,11,18]],"date-time":"2024-11-18T00:00:00Z","timestamp":1731888000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Trimethylamine-N-oxide (TMAO) is a gut microbiota-derived metabolite, the production of which in vivo is mainly regulated by dietary choices, gut microbiota, and the hepatic enzyme flavin monooxygenase (FMO), while its elimination occurs via the kidneys. The TMAO level is positively correlated with the risk of developing cardiovascular diseases. Recent studies have found that TMAO plays an important role in the development of ischemic stroke. In this review, we describe the relationship between TMAO and ischemic stroke risk factors (hypertension, diabetes, atrial fibrillation, atherosclerosis, thrombosis, etc.), disease risk, severity, prognostic outcomes, and recurrence and discuss the possible mechanisms by which they interact. Importantly, TMAO induces atherosclerosis and thrombosis through lipid metabolism, foam cell formation, endothelial dysfunction (via inflammation, oxidative stress, and pyroptosis), enhanced platelet hyper-reactivity, and the upregulation and activation of vascular endothelial tissue factors. Although the pathogenic mechanisms underlying TMAO\u2019s aggravation of disease severity and its effects on post-stroke neurological recovery and recurrence risk remain unclear, they may involve inflammation, astrocyte function, and pro-inflammatory monocytes. In addition, this paper provides a summary and evaluation of relevant preclinical and clinical studies on interventions regarding the gut-microbiota-dependent TMAO level to provide evidence for the prevention and treatment of ischemic stroke through the gut microbe\u2013TMAO pathway.<\/jats:p>","DOI":"10.3390\/biom14111463","type":"journal-article","created":{"date-parts":[[2024,11,18]],"date-time":"2024-11-18T05:36:45Z","timestamp":1731908205000},"page":"1463","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Gut Microbe-Generated Metabolite Trimethylamine-N-Oxide and Ischemic Stroke"],"prefix":"10.3390","volume":"14","author":[{"given":"Zhen","family":"Li","sequence":"first","affiliation":[{"name":"Department of Neurology, The First Affiliated Hospital of Soochow University, No. 899 Pinghai Road, Suzhou 215006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyi","family":"He","sequence":"additional","affiliation":[{"name":"Department of Neurology, The First Affiliated Hospital of Soochow University, No. 899 Pinghai Road, Suzhou 215006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5663-8984","authenticated-orcid":false,"given":"Qi","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Neurology, The First Affiliated Hospital of Soochow University, No. 899 Pinghai Road, Suzhou 215006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xulong","family":"Yin","sequence":"additional","affiliation":[{"name":"Department of Neurology, The First Affiliated Hospital of Soochow University, No. 899 Pinghai Road, Suzhou 215006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,18]]},"reference":[{"key":"ref_1","unstructured":"GBD 2019 Stroke Collaborators (2021). 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