This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement no. 814168.
CORDIS PROJECT ID 218110.
Abstract: The aryl hydrocarbon receptor (AhR) is a nuclear protein which, upon association with certain endogenous and exogenous ligands, translocates into the nucleus, binds DNA and regulates gene expression. Tryptophan (Trp) metabolites are one of the most important endogenous AhR ligands. The intestinal microbiota is a critical player in human intestinal homeostasis. Many of its effects are mediated by an assembly of metabolites, including Trp metabolites. In the intestine, Trp is metabolized by three main routes, leading to kynurenine, serotonin, and indole derivative synthesis under the direct or indirect involvement of the microbiota. Disturbance in Trp metabolism and/or AhR activation is strongly associated with multiple gastrointestinal, neurological and metabolic disorders, suggesting Trp metabolites/AhR signaling modulation as an interesting therapeutic perspective. In this review, we describe the most recent advances concerning Trp metabolism and AhR signaling in human health and disease, with a focus on nutrition as a potential therapy to modulate Trp metabolites acting on AhR. A better understanding of the complex balance between these pathways in human health and disease will yield therapeutic opportunities. View open-access Full-Text.
Figure above provides a schematic overview of potential mechanisms of nutritional therapies to modulate microbiota dependent tryptophan (Trp) metabolism and AhR signaling activation in order to improve outcome of intestinal and metabolic diseases (A), neurological diseases (B) and cancer (C). Green arrows represent IDO1 production, large green arrows represent high production and the narrow arrows represent low production. Brown arrows represent AhR activation, large brown arrows represent high activation of AhR, and the narrow arrows represent low activation of AhR.
Tue, 22 September