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

(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.