D-Tryptophan suppresses enteric pathogen and pathobionts and prevents colitis by modulating microbial tryptophan metabolism

Natsumi Seki, Tatsuki Kimizuka, Monica Gondo, Genki Yamaguchi, Yuki Sugiura, Masahiro Akiyama, Kyosuke Yakabe, Jun Uchiyama, Seiichiro Higashi, Takeshi Haneda, Makoto Suematsu, Koji Hase, Yungi Kim

Research output: Contribution to journalArticlepeer-review

Abstract

D-Amino acids (D-AAs) have various functions in mammals and microbes. D-AAs are produced by gut microbiota and can act as potent bactericidal molecules. Thus, D-AAs regulate the ecological niche of the intestine; however, the actual impacts of D-AAs in the gut remain unknown. In this study, we show that D-Tryptophan (D-Trp) inhibits the growth of enteric pathogen and colitogenic pathobionts. The growth of Citrobacter rodentium in vitro is strongly inhibited by D-Trp treatment. Moreover, D-Trp protects mice from lethal C. rodentium infection via reduction of the pathogen. Additionally, D-Trp prevents the development of experimental colitis by the depletion of specific microbes in the intestine. D-Trp increases the intracellular level of indole acrylic acid (IA), a key molecule that determines the susceptibility of enteric microbes to D-Trp. Treatment with IA improves the survival of mice infected with C. rodentium. Hence, D-Trp could act as a gut environmental modulator that regulates intestinal homeostasis.

Original languageEnglish
Article number104838
JournaliScience
Volume25
Issue number8
DOIs
Publication statusPublished - 2022 Aug 19

Keywords

  • cell biology
  • cellular physiology
  • microbiology
  • microbiome

ASJC Scopus subject areas

  • General

Fingerprint

Dive into the research topics of 'D-Tryptophan suppresses enteric pathogen and pathobionts and prevents colitis by modulating microbial tryptophan metabolism'. Together they form a unique fingerprint.

Cite this