Tryptophan Metabolism: A Link Between the Gut Microbiota and Brain

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ABSTRACT

The gut-brain axis (GBA) is a bilateral communication network between the gastrointestinal (GI) tract and the central nervous system. The essential amino acid tryptophan contributes to the normal growth and health of both animals and humans and, importantly, exerts modulatory functions at multiple levels of the GBA. Tryptophan is the sole precursor of serotonin, which is a key monoamine neurotransmitter participating in the modulation of central neurotransmission and enteric physiological function. In addition, tryptophan can be metabolized into kynurenine, tryptamine, and indole, thereby modulating neuroendocrine and intestinal immune responses. The gut microbial influence on tryptophan metabolism emerges as an important driving force in modulating tryptophan metabolism. Here, we focus on the potential role of tryptophan metabolism in the modulation of brain function by the gut microbiota. We start by outlining existing knowledge on tryptophan metabolism, including serotonin synthesis and degradation pathways of the host, and summarize recent advances in demonstrating the influence of the gut microbiota on tryptophan metabolism. The latest evidence revealing those mechanisms by which the gut microbiota modulates tryptophan metabolism, with subsequent effects on brain function, is reviewed. Finally, the potential modulation of intestinal tryptophan metabolism as a therapeutic option for brain and GI functional disorders is also discussed.

tryptophan metabolism
serotonin
kynurenine
microbial tryptophan metabolites
gut-brain axis
gut microbiota
irritable bowel syndrome
depression

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This study was funded by the National Natural Science Foundation of China (31430082) and the National Key Basic Research Program of China (2013CB127300).

Author disclosures: The authors report no conflicts of interest.

Abbreviations: Ah, aryl hydrocarbon receptor; ASD, autism spectrum disorder; BBB, blood-brain barrier; CNS, central nervous system; EC, enterochromaffin cell; ENS, enteric nervous system; FOS, fructooligosaccharides; GBA, gut-brain axis; GF, germ free; GI, gastrointestinal; HC, healthy control; HDAC, histone deacetylase; IAA, indole-3-acetic acid; IAld, indole-3-aldehyde; IBS, irritable bowel syndrome; IDO, indoleamine 2,3-dioxygenase; ILA, indole-3-lactic acid; IPA, indolic-3-propionic acid; KYNA, kynurenic acid; MAO, monoamine oxidase; miRNA, micro RNA; NMDA, N-methyl D-aspartate; QUIN, quinolinic acid; SERT, serotonin-selective reuptake transporter; STAT1, signal transducer and activator of transcription 1; TDO, tryptophan 2,3-dioxygenase; TLR, Toll-like receptor; TnaA, tryptophanase; TPH, tryptophan hydroxylase; TrpD, tryptophan decarboxylase.