Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
Miyarisan Pharmaceutical Co., Research Laboratory, Tokyo, Japan.
Int Immunol. 2024 Nov 14;36(12):601-616. doi: 10.1093/intimm/dxae035.
The intricate and dynamic tryptophan (Trp) metabolic pathway in both the microbiome and host cells highlights its profound implications for health and disease. This pathway involves complex interactions between host cellular and bacteria processes, producing bioactive compounds such as 5-hydroxytryptamine (5-HT) and kynurenine derivatives. Immune responses to Trp metabolites through specific receptors have been explored, highlighting the role of the aryl hydrocarbon receptor in inflammation modulation. Dysregulation of this pathway is implicated in various diseases, such as Alzheimer's and Parkinson's diseases, mood disorders, neuronal diseases, autoimmune diseases such as multiple sclerosis (MS), and cancer. In this article, we describe the impact of the 5-HT, Trp, indole, and Trp metabolites on health and disease. Furthermore, we review the impact of microbiome-derived Trp metabolites that affect immune responses and contribute to maintaining homeostasis, especially in an experimental autoimmune encephalitis model of MS.
色氨酸（Trp）代谢途径在微生物组和宿主细胞中的错综复杂和动态特性突显了其对健康和疾病的深远影响。该途径涉及宿主细胞和细菌之间的复杂相互作用，产生生物活性化合物，如 5-羟色胺（5-HT）和犬尿氨酸衍生物。通过特定受体对 Trp 代谢物的免疫反应已被探索，强调了芳基烃受体在炎症调节中的作用。该途径的失调与各种疾病有关，如阿尔茨海默病和帕金森病、情绪障碍、神经疾病、多发性硬化症（MS）等自身免疫性疾病以及癌症。在本文中，我们描述了 5-HT、Trp、吲哚和 Trp 代谢物对健康和疾病的影响。此外，我们还综述了微生物组衍生的 Trp 代谢物对免疫反应的影响，这些代谢物有助于维持体内平衡，特别是在 MS 的实验性自身免疫性脑脊髓炎模型中。
