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. 2018 Aug 17;9:3294. doi: 10.1038/s41467-018-05470-4

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© The Author(s) 2018

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 1 — Mechanisms of action of microbial tryptophan catabolites on host physiology. Degradation of dietary proteins leads to the release of tryptophan, which is converted into various catabolites by the gut microbiota. The tryptophan catabolites include indole, tryptamine, indoleethanol (IE), indolepropionic acid (IPA), indolelactic acid (ILA), indoleacetic acid (IAA), skatole, indolealdehyde (IAld) and indoleacrylic acid (IA) and may affect host physiology in numerous ways. Indole, IPA and IA affect mucosal homeostasis by decreased intestinal permeability possibly mediated by the pregnane X receptor (PXR). Indole induces the release of glucagon-like peptide 1 (GLP-1) in enteroendocrine L-cells. GLP-1 is known to suppress appetite, insulin secretion and to slow gastric emptying. Several tryptophan catabolites act on the aryl hydrocarbon receptor (AHR) found in intestinal immune cells and thereby alter innate and adaptive immune responses in a ligand-specific fashion (e.g. IAld induces increased production of interleukin-22 (IL-22) via AHR activation). Tryptamine induces the release of 5-hydroxytryptamine (5-HT, serotonin) by enterochromaffin cells. 5-HT stimulates gastrointestinal motility by acting on enteric nervous system neurons. Tryptophan catabolites are absorbed through the intestinal epithelium and enter the bloodstream where some (e.g. IPA, IE, IA) have anti-oxidative and anti-inflammatory effects, whereas indoxyl-sulfate (IS), which is produced in the liver from indole by the actions of CYP2E1 and sulfotransferases (SULT), has cytotoxic effects in high concentrations