Nat. Microbiol. 1, 16125 (2016)

Credit: NATURE MICROBIOLOGY

D-amino acids (D-aa) are not incorporated into proteins by ribosomes but function as signaling molecules, such as in mammalian neurotransmission, and as regulators of bacterial cell wall formation. Although bacteria have not been shown to produce D-aa previously, secretion of D-aa by commensal bacteria may affect host physiology. To test this, Sasabe et al. looked for D-aa and the D-aa-metabolizing enzyme DAO in the intestines of germ-free (GF) mice and mice free of only certain pathogens (SPF). The caeca of SPF mice expressed DAO and contained D-Ala, D-Asp, D-Glu and D-Pro, at levels much higher than in GF mice, which contained only relatively low levels of D-Asp. As well, DAO was expressed in the small intestine of SPF mice, secreted by enterocytes and goblet cells, and to a much lesser extent in GF mice. Lumenal, mucosal and intraepithelial concentrations of D-ala were higher in DAO-mutant mice. The authors also found that DAO is bactericidal against several enteric pathogens, including Vibrio cholerae, in vitro, through the production of H2O2 from oxidation of D-aa. Also, a microbiome analysis showed that the overall intestinal microbiota composition is altered in the absence of DAO. These results suggest that the microbiota influences the production of DAO in the intestine, playing a general role in protection of the mucosal surface.