Saha Biki, Banerjee Antara, Pathak Rupak, Duttaroy Asim K, Pathak Surajit
Medical Biotechnology, Faculty of Allied Health Sciences, Chettinad Academy of Research and Education (CARE), Chettinad Hospital and Research Institute (CHRI), Chennai, India.
Division of Radiation Health, Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
Biomed Pharmacother. 2025 Nov;192:118592. doi: 10.1016/j.biopha.2025.118592. Epub 2025 Sep 22.
The gut microbiota play a crucial role in cancer pathogenesis, partly through metabolites derived from dietary components or host compounds. Among these, trimethylamine N-oxide (TMAO), a secondary gut microbiota-derived metabolite has gained attention for its potential link to cancer. TMAO is formed when gut microbes convert dietary choline, carnitine, and betaine into trimethylamine (TMA), which is then oxidized in the liver by FMO3. While TMAO has been well studied in cardiovascular, kidney, and metabolic diseases, growing evidence links elevated TMAO levels to increased risks of colorectal cancer (CRC) and hepatocellular carcinoma (HCC). Although the exact mechanisms remain unclear, TMAO appears to contribute to cancer progression by promoting inflammation, oxidative stress, endoplasmic reticulum stress, and insulin resistance. This review discusses the dietary and microbial pathways involved in TMAO synthesis, its role in cancer progression, and critically evaluates the current literature on its potential contribution to cancer. Understanding the role of TMAO could offer new strategies for cancer prevention and therapy that target the gut microbiota and their metabolites.
肠道微生物群在癌症发病机制中起着关键作用，部分原因是通过源自饮食成分或宿主化合物的代谢产物。其中，三甲胺N-氧化物（TMAO）作为一种源自肠道微生物群的次级代谢产物，因其与癌症的潜在联系而受到关注。当肠道微生物将饮食中的胆碱、肉碱和甜菜碱转化为三甲胺（TMA）时，TMAO就会形成，然后TMA在肝脏中被FMO3氧化。虽然TMAO在心血管、肾脏和代谢疾病方面已经得到了充分研究，但越来越多的证据表明，TMAO水平升高与结直肠癌（CRC）和肝细胞癌（HCC）风险增加有关。尽管确切机制尚不清楚，但TMAO似乎通过促进炎症、氧化应激、内质网应激和胰岛素抵抗来促进癌症进展。本文综述了参与TMAO合成的饮食和微生物途径，其在癌症进展中的作用，并批判性地评估了当前关于其对癌症潜在贡献的文献。了解TMAO的作用可能为针对肠道微生物群及其代谢产物的癌症预防和治疗提供新策略。
