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Zhou, Yuhua; Zhang, Yuwei; Jin, Shengkai; Lv, Jing; Li, Menglu; Feng, Ninghan
Biomedicine & pharmacotherapy, August 2024, 2024-08-00, 20240801, 2024-08-01, Volume: 177Journal Article
An expanding body of research indicates a correlation between the gut microbiota and various diseases. Metabolites produced by the gut microbiota act as mediators between the gut microbiota and the host, interacting with multiple systems in the human body to regulate physiological or pathological functions. However, further investigation is still required to elucidate the underlying mechanisms. One such metabolite involved in choline metabolism by gut microbes is trimethylamine (TMA), which can traverse the intestinal epithelial barrier and enter the bloodstream, ultimately reaching the liver where it undergoes oxidation catalyzed by flavin-containing monooxygenase 3 (FMO3) to form trimethylamine N-oxide (TMAO). While some TMAO is eliminated through renal excretion, remaining amounts circulate in the bloodstream, leading to systemic inflammation, endoplasmic reticulum (ER) stress, mitochondrial stress, and disruption of normal physiological functions in humans. As a representative microbial metabolite originating from the gut, TMAO has significant potential both as a biomarker for monitoring disease occurrence and progression and for tailoring personalized treatment strategies for patients. This review provides an extensive overview of TMAO sources and its metabolism in human blood, as well as its impact on several major human diseases. Additionally, we explore the latest research areas related to TMAO along with future directions. Display omitted •Review of the known pathways of TMAO production and the catalytic enzymes involved.•Summary of recent advances in the role of TMAO in cancer and other diseases.•TMAO can enhance the response to anti-PD-1 immunotherapy in tumors.•TMAO plays a crucial role in the pathogenesis of various diseases.•Discussion of future prospects and directions for TMAO research.
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