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Methods This narrative review included a literature search using the PubMed and Web of Science databases with the keywords: (TMAO OR Trimethylamine N-oxide) AND (clinical study OR animal model OR in vitro study)

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Under conditions of chronic stress or systemic inflammation, enzymes such as indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO) are upregulated, diverting TRP metabolism away from 5-HT synthesis toward KYN production, with profound consequences for both peripheral physiology and central nervous system (CNS) function