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.
Highlights
The mammalian intestine contains a complex symbiosis of host epithelial and immune cells, and luminal dietary antigens and microorganisms [1]
We report the most recent insights regarding the Trp metabolism/aryl hydrocarbon receptor (AhR) axis in health and disease, with a focus on nutrition as a potential therapy to modulate adverse Trp metabolism acting on AhR
In patients suffering from metabolic syndrome, an overactivation of IDO1 has been reported with increased Kyn levels in serum and increased Kyn/Trp ratio
Summary
The mammalian intestine contains a complex symbiosis of host epithelial and immune cells, and luminal dietary antigens and microorganisms [1]. The intestine harbors a dense and diverse microbiota composed by commensal bacteria, fungi, archaea and virus communities [2] These unique microbial communities have co-developed with the host to reach a symbiotic balance called homeostasis [3]. The intestinal microbiota plays a major role in many important physiological functions, such as metabolic, nutritional and immune homeostasis [4]. These effects are mediated by direct microbiota-host interactions and by microbial- and host-derived metabolites [4,5]. Upon agonist binding (such as Trp-derived metabolites), AhR translocates to the nucleus, where it binds DNA and controls gene expressions in a ligand-specific, cell-type-specific and context-specific manner [16,17]. We report the most recent insights regarding the Trp metabolism/AhR axis in health and disease, with a focus on nutrition as a potential therapy to modulate adverse Trp metabolism acting on AhR
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