<sub>D</sub>-Tryptophan suppresses enteric pathogen and pathobionts and prevents colitis by modulating microbial tryptophan metabolism.

Overview

_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.