摘要:SummaryD-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 ofD-AAs in the gut remain unknown. In this study, we show thatD-Tryptophan (D-Trp) inhibits the growth of enteric pathogen and colitogenic pathobionts. The growth ofCitrobacter rodentium in vitrois strongly inhibited byD-Trp treatment. Moreover,D-Trp protects mice from lethalC.rodentiuminfection 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 toD-Trp. Treatment with IA improves the survival of mice infected withC.rodentium. Hence,D-Trp could act as a gut environmental modulator that regulates intestinal homeostasis.Graphical abstractDisplay OmittedHighlights•D-Trp inhibits the growth ofCitrobacter rodentium in vitroandin vivo•D-Trp suppresses experimental colitis by the depletion of specific gut microbes•IA is the metabolite that determines the susceptibility of enteric microbes toD-TrpCell biology; Cellular physiology; Microbiology; Microbiome