Impact of the Gut Microbiota on Intestinal Immunity Mediated by Tryptophan Metabolism

By Jing Gao, K. Xu, Hongnan Liu, Gang Liu, M. Bai, Can Peng, Tiejun Li, Yulong Yin. Frontiers in Cellular and Infection Microbiology, 2018

1,134 citations recorded by the source corpus.

The gut microbiota influences the health of the host, especially with regard to gut immune homeostasis and the intestinal immune response. In addition to serving as a nutrient enhancer, L-tryptophan (Trp) plays crucial roles in the balance between intestinal immune tolerance and gut microbiota maintenance. Recent discoveries have underscored that changes in the microbiota modulate the host immune system by modulating Trp metabolism. Moreover, Trp, endogenous Trp metabolites (kynurenines, serotonin, and melatonin), and bacterial Trp metabolites (indole, indolic acid, skatole, and tryptamine) have profound effects on gut microbial composition, microbial metabolism, the host's immune system, the host-microbiome interface, and host immune system–intestinal microbiota interactions. The aryl hydrocarbon receptor (AhR) mediates the regulation of intestinal immunity by Trp metabolites (as ligands of AhR), which is beneficial for immune homeostasis. Among Trp metabolites, AhR ligands consist of endogenous metabolites, including kynurenine, kynurenic acid, xanthurenic acid, and cinnabarinic acid, and bacterial metabolites, including indole, indole propionic acid, indole acetic acid, skatole, and tryptamine. Additional factors, such as aging, stress, probiotics, and diseases (spondyloarthritis, irritable bowel syndrome, inflammatory bowel disease, colorectal cancer), which are associated with variability in Trp metabolism, can influence Trp–microbiome–immune system interactions in the gut and also play roles in regulating gut immunity. This review clarifies how the gut microbiota regulates Trp metabolism and identifies the underlying molecular mechanisms of these interactions. Increased mechanistic insight into how the microbiota modulates the intestinal immune system through Trp metabolism may allow for the identification of innovative microbiota-based diagnostics, as well as appropriate nutritional supplementation of Trp to prevent or alleviate intestinal inflammation. Moreover, this review provides new insight regarding the influence of the gut microbiota on Trp metabolism. Additional comprehensive analyses of targeted Trp metabolites (including endogenous and bacterial metabolites) are essential for experimental preciseness, as the influence of the gut microbiota cannot be neglected, and may explain contradictory results in the literature.

Subfields: Biological Psychiatry, General Health Professions, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/111de19cf6a9a110fd3918b17cd2d6527d93e237

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Citations in the corpus

The Continuum of Aging and Age-Related Diseases: Common Mechanisms but Different Rates (2018, background): “It has been recently showed that the GM undergoes profound changes with age (173), which likely contribute to inflammaging (174) and can have profound effects on the brain, owing to the increased abundance with age of bacteria involved in the tryptophan metabolism pathway (175), in agreement with th”
Metabolomics for Investigating Physiological and Pathophysiological Processes. (2019, background): “In particular, the gut microbiome is able to metabolize complex polysaccharides (fiber) into short-chain fatty acids (SCFAs) (315), it is able to processes many polyphenolic compounds into simple phenolic acids (339), it is able to metabolize tryptophan to produce a variety of unpleasant smelling an”
Gut Microbiota Regulation of Tryptophan Metabolism in Health and Disease. (2018, positive): “Kna exhibits mucosal protective and immunoregulatory effects, probably through its G protein-coupled receptor, GPR35, which is mostly expressed in epithelial and immune cells (Gao et al., 2018).”