Metabolites of microbiota response to tryptophan and intestinal mucosal immunity: A therapeutic target to control intestinal inflammation

Jie Zhang, Shengwei Zhu, Ning Ma, Lee J. Johnston, Chaodong Wu, Xi Ma

Research output: Contribution to journalReview articlepeer-review

69 Scopus citations

Abstract

In a complex, diverse intestinal environment, commensal microbiota metabolizes excessive dietary tryptophan to produce more bioactive metabolites connecting with kinds of diverse process, such as host physiological defense, homeostasis, excessive immune activation and the progression and outcome of different diseases, such as inflammatory bowel disease, irritable bowel syndrome and others. Although commensal microbiota includes bacteria, fungi, and protozoa and all that, they often have the similar metabolites in tryptophan metabolism process via same or different pathways. These metabolites can work as signal to activate the innate immunity of intestinal mucosa and induce the rapid inflammation response. They are critical in reconstruction of lumen homeostasis as well. This review aims to seek the potential function and mechanism of microbiota-derived tryptophan metabolites as targets to regulate and shape intestinal immune function, which mainly focused on two aspects. First, analyze the character of tryptophan metabolism in bacteria, fungi, and protozoa, and assess the functions of their metabolites (including indole and eight other derivatives, serotonin (5-HT) and d-tryptophan) on regulating the integrity of intestinal epithelium and the immunity of the intestinal mucosa. Second, focus on the mediator and pathway for their recognition, transfer and crosstalk between microbiota-derived tryptophan metabolites and intestinal mucosal immunity. Disruption of intestinal homeostasis has been described in different intestinal inflammatory diseases, available data suggest the remarkable potential of tryptophan-derived aryl hydrocarbon receptor agonists, indole derivatives on lumen equilibrium. These metabolites as preventive and therapeutic interventions have potential to promote proinflammatory or anti-inflammatory responses of the gut.

Original languageEnglish (US)
Pages (from-to)1061-1088
Number of pages28
JournalMedicinal Research Reviews
Volume41
Issue number2
DOIs
StatePublished - Mar 2021

Bibliographical note

Funding Information:
The authors profound admiration and respect go to researchers who in this field and in their laboratories. The authors apologize to scientists whose work is in this field if their papers are not cited owing to space limitations. This study 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), the Beijing Characteristic High Level Backbone Professional Group Construction Project (PXM2020‐157102‐000060), and the 111 Project (B16044).

Funding Information:
The authors profound admiration and respect go to researchers who in this field and in their laboratories. The authors apologize to scientists whose work is in this field if their papers are not cited owing to space limitations. This study 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), the Beijing Characteristic High Level Backbone Professional Group Construction Project (PXM2020-157102-000060), and the 111 Project (B16044).

Publisher Copyright:
© 2020 Wiley Periodicals LLC

Keywords

  • intestinal inflammatory diseases
  • microbes
  • mucosal immunity
  • tryptophan metabolites

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