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Dietary phosphatidylcholine and choline are metabolized by gut bacteria to generate trimethylamine (TMA). Upon entering the bloodstream, TMA is oxidized by host liver enzymes to trimethylamine N-oxide (TMAO), a known independent risk factor for various systemic diseases, including atherosclerosis, thrombosis, and chronic kidney disease. Within this complex \u201cdiet\u2013gut\u2013host\u201d metabolic axis, the microbial choline TMA-lyase (CutC) acts as the key rate-limiting enzyme that catalyzes the cleavage of choline to produce TMA. This review systematically summarizes the discovery history, enzymatic structural characteristics, and catalytic mechanism of CutC, highlighting its potential as a microbial metabolic target for treating associated diseases. By specifically analyzing existing inhibitor strategies and interventions, this article emphasizes the extensive potential of specific targeting of the CutC enzyme in precisely regulating the functions of the microecology.<\/jats:p>","DOI":"10.3390\/nu18111659","type":"journal-article","created":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T12:14:52Z","timestamp":1779452092000},"page":"1659","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Gut Microbial Choline TMA-Lyase CutC: From Metabolic Mechanism to a Novel Therapeutic Target for Diseases"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-0216-2329","authenticated-orcid":false,"given":"Na","family":"Zhang","sequence":"first","affiliation":[{"name":"School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gan","family":"Luo","sequence":"additional","affiliation":[{"name":"School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyan","family":"Gao","sequence":"additional","affiliation":[{"name":"School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1038\/s41579-020-0433-9","article-title":"Gut microbiota in human metabolic health and disease","volume":"19","author":"Fan","year":"2021","journal-title":"Nat. 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