The kynurenine pathway is the major route of tryptophan degradation, producing kynurenine (Kyn) and downstream metabolites including 3-hydroxykynurenine and quinolinic acid. Tryptophan metabolism is one of the main metabolic interfaces through which gut microbes influence host immune function.
Kynurenine itself is a well-recognized immunoregulatory metabolite, implicated in immune tolerance and tumor progression by modulating immune cell differentiation and function, and classically described as a ligand for the aryl hydrocarbon receptor (AHR). Raised kynurenine concentrations have been reported across multiple cancer types and linked to immunosuppressive macrophage polarization and adverse clinical outcomes, which has motivated therapeutic efforts to lower it, for example with kynureninase-based approaches.
The Kyn/Trp ratio is commonly used as an index of how actively the pathway is running in a given sample.
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Source papers
- Chronic Stress Promotes Gastric Cancer Metastasis by Inducing Microbiota-Associated Kynurenine Accumulation and Macrophage Remodeling doi:10.1002/advs.77612