@article{348dac7c51de4de783feafec4d4bcde2,
title = "D-Tryptophan suppresses enteric pathogen and pathobionts and prevents colitis by modulating microbial tryptophan metabolism",
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.",
keywords = "cell biology, cellular physiology, microbiology, microbiome",
author = "Natsumi Seki and Tatsuki Kimizuka and Monica Gondo and Genki Yamaguchi and Yuki Sugiura and Masahiro Akiyama and Kyosuke Yakabe and Jun Uchiyama and Seiichiro Higashi and Takeshi Haneda and Makoto Suematsu and Koji Hase and Kim, {Yun Gi}",
note = "Funding Information: This study was funded by Meiji Holdings Co. S.H. is an employee of Co-Creation Center, Meiji Holdings Co., Ltd. The other authors declare no competing interests. Funding Information: This work was supported by research grants from the JSPS KAKENHI (JP17H05068 and JP20H03490 to Y.-G.K.), AMED (JP18gm6010004h0003 to Y.-G.K.), Takeda Science Foundation (to Y.-G.K.), the Naito Foundation (to Y.-G.K.), Yakult Bio-Science Foundation (to Y.-G.K.), and Mochida Memorial Foundation for Medical and Pharmaceutical Research (to Y.-G.K.). Y.-G.K. conceived the study and designed the experiments; N. S. T. K. M. G. G. Y. Y. S. K. Y. J. U. M. A. S. H. and Y.-G.K. collected samples and conducted the experiments; N. S. T. K. M. G. G. Y. Y. S. K. Y. J. U. M. A. S. H. T. H. M. S. K. H. and Y.-G. K. analyzed data; N. S. G.Y. M. A. and Y.-G. K. prepared the article. Y.-G. K. supervised the project. All authors read and approved the final article. This study was funded by Meiji Holdings Co. S.H. is an employee of Co-Creation Center, Meiji Holdings Co. Ltd. The other authors declare no competing interests. Funding Information: This work was supported by research grants from the JSPS KAKENHI ( JP17H05068 and JP20H03490 to Y.-G.K.), AMED ( JP18gm6010004h0003 to Y.-G.K.), Takeda Science Foundation (to Y.-G.K.), the Naito Foundation (to Y.-G.K.), Yakult Bio-Science Foundation (to Y.-G.K.), and Mochida Memorial Foundation for Medical and Pharmaceutical Research (to Y.-G.K.). Publisher Copyright: {\textcopyright} 2022 The Author(s)",
year = "2022",
month = aug,
day = "19",
doi = "10.1016/j.isci.2022.104838",
language = "English",
volume = "25",
journal = "iScience",
issn = "2589-0042",
publisher = "Elsevier Inc.",
number = "8",
}