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.
Nutrients. 2020 Sep 17;12(9):2846. doi: 10.3390/nu12092846.
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.
芳香烃受体 (AhR) 是一种核蛋白，与某些内源性和外源性配体结合后，会转移到细胞核内，与 DNA 结合并调节基因表达。色氨酸 (Trp) 代谢物是最重要的内源性 AhR 配体之一。肠道微生物群是人体肠道内稳态的关键参与者。其许多作用是通过一组代谢物介导的，包括色氨酸代谢物。在肠道中，色氨酸通过三种主要途径代谢，在微生物的直接或间接参与下，导致犬尿氨酸、血清素和吲哚衍生物的合成。色氨酸代谢紊乱和/或 AhR 激活与多种胃肠道、神经和代谢紊乱密切相关，这表明色氨酸代谢物/AhR 信号转导的调节是一种很有前途的治疗方法。在这篇综述中，我们描述了色氨酸代谢和 AhR 信号在人类健康和疾病中的最新进展，重点介绍了营养作为一种潜在的治疗方法，以调节作用于 AhR 的色氨酸代谢物。更好地了解这些途径在人类健康和疾病中的复杂平衡将产生治疗机会。
