The tryptophan metabolic pathway of the microbiome and host cells in health and disease

Author:

Miyamoto Kentaro12,Sujino Tomohisa34ORCID,Kanai Takanori1

Affiliation:

1. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine , Tokyo , Japan

2. Miyarisan Pharmaceutical Co., Research Laboratory , Tokyo , Japan

3. Center for Diagnostic and Therapeutic Endoscopy, Keio University School of Medicine , Tokyo , Japan

4. Keio Global Research Institute, Keio University , Tokyo , Japan

Abstract

Abstract 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.

Funder

Japan Science and Technology Agency

Japan Agency for Medical Research and Development

Publisher

Oxford University Press (OUP)

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