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Nutritional Therapy to Modulate Tryptophan Metabolism and Aryl Hydrocarbon-Receptor Signaling Activation in Human Diseases

Department of Pediatric Gastroenterology and Nutrition, Amsterdam University Medical Centers, Emma Children’s Hospital, 1105 AZ Amsterdam, The Netherlands
Tytgat Institute for Liver and Intestinal Research, Amsterdam Gastroenterology and Metabolism, Academic Medical Center, University of Amsterdam, 1105 BK Amsterdam, The Netherlands
Department of Pediatric Surgery, Amsterdam University Medical Centers, 1105 AZ Amsterdam, The Netherlands
Department of Surgery, University of Bonn, 53127 Bonn, Germany
Department of Pediatrics, Dalhousie University, Halifax, NS B3K 6R8, Canada
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Nutrients 2020, 12(9), 2846;
Received: 17 August 2020 / Revised: 10 September 2020 / Accepted: 12 September 2020 / Published: 17 September 2020
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 Full-Text
Keywords: microbiota; tryptophan; AhR; nutritional therapy; human diseases microbiota; tryptophan; AhR; nutritional therapy; human diseases
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Ghiboub, M.; Verburgt, C.M.; Sovran, B.; Benninga, M.A.; de Jonge, W.J.; Van Limbergen, J.E. Nutritional Therapy to Modulate Tryptophan Metabolism and Aryl Hydrocarbon-Receptor Signaling Activation in Human Diseases. Nutrients 2020, 12, 2846.

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