AUTHOR=Qin Na , Xie Xiaodi , Deng Rong , Gao Shiman , Zhu Ting TITLE=The role of the tryptophan metabolites in gut microbiota-brain axis and potential treatments: a focus on ischemic stroke JOURNAL=Frontiers in Pharmacology VOLUME=Volume 16 - 2025 YEAR=2025 URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2025.1578018 DOI=10.3389/fphar.2025.1578018 ISSN=1663-9812 ABSTRACT=Gut microbiota disturbances can elevate the risk of stroke by contributing to cerebrovascular events. Particularly, the gut tryptophan (TRP) metabolite is an essential mediator of the gut-brain axis. This review highlights the role of TRP metabolism in stroke, the influence of intestinal microbiomes on stroke pathology via TRP metabolism, and the gut-brain axis interactions. Recent studies indicate that various bioactive molecules produced via TRP metabolism can regulate various neurological functions and interrupt stroke pathophysiology. Moreover, the relationship between gut TRP metabolism and stroke development has been verified. TRP metabolism involves three pathways: kynurenine, 5-hydroxytryptamine, and indole, which potentially regulate post-stroke, may function as aryl hydrocarbon receptor agonists to modify neuronal excitotoxicity, and offer crucial targets for stroke treatment. This suggests that modulating TRP metabolite levels through various methods can enhance the prognosis of central nervous system diseases and restore microbiota-gut-brain axis functions.