Host-microbiome interactions: the aryl hydrocarbon receptor as a critical node in tryptophan metabolites to brain signaling

Gut Microbes. 2020 Sep 2;11(5):1203-1219. doi: 10.1080/19490976.2020.1758008. Epub 2020 May 13.

Abstract

Tryptophan (Trp) is not only a nutrient enhancer but also has systemic effects. Trp metabolites signaling through the well-known aryl hydrocarbon receptor (AhR) constitute the interface of microbiome-gut-brain axis. However, the pathway through which Trp metabolites affect central nervous system (CNS) function have not been fully elucidated. AhR participates in a broad variety of physiological and pathological processes that also highly relevant to intestinal homeostasis and CNS diseases. Via the AhR-dependent mechanism, Trp metabolites connect bidirectional signaling between the gut microbiome and the brain, mediated via immune, metabolic, and neural (vagal) signaling mechanisms, with downstream effects on behavior and CNS function. These findings shed light on the complex Trp regulation of microbiome-gut-brain axis and add another facet to our understanding that dietary Trp is expected to be a promising noninvasive approach for alleviating systemic diseases.

Keywords: Tryptophan metabolites; aryl hydrocarbon receptor (AhR); central nervous system (CNS); microbiome-gut-brain axis; vagal.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / chemistry
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Brain / metabolism*
  • Gastrointestinal Microbiome / physiology*
  • Gastrointestinal Tract / metabolism*
  • Gastrointestinal Tract / microbiology
  • Homeostasis
  • Host Microbial Interactions*
  • Humans
  • Metabolic Networks and Pathways
  • Neural Pathways
  • Receptors, Aryl Hydrocarbon / chemistry
  • Receptors, Aryl Hydrocarbon / metabolism*
  • Signal Transduction
  • Tryptophan / metabolism*
  • Vagus Nerve / physiology

Substances

  • AHR protein, human
  • Basic Helix-Loop-Helix Transcription Factors
  • Receptors, Aryl Hydrocarbon
  • Tryptophan

Grants and funding

This work was supported by the National Key R&D Program of China (2018YFD0500601 and 2017YFD0500501), the National Natural Science Foundation of China (31930106, 31829004 and 31722054), the National Ten-thousand Talents Program of China (23070201) and the 111 project (B16044).