| description |
While L-amino acids are the building blocks for proteins synthesized in ribosomes in all kingdoms of life, D-amino acids (D-aa) are important in non-ribosome based functions. Mammals synthesize D-Ser and D-Asp, primarily in the central nervous system, where D-Ser is critical for neurotransmission. Bacteria synthesize a largely distinct set of D-aa, which become integral components of the cell wall and are also released as free D-aa. However, the impact of free microbial D-aa on host physiology at the host-microbial interface has not been explored. Here, we show that the mouse intestine is rich in free D-aa that are derived from the microbiota. Furthermore, the microbiota induces production of D-amino acid oxidase (DAO) by intestinal epithelial cells, including goblet cells, which secrete the enzyme into the lumen. Oxidization of intestinal D-aa by DAO, which yields the antimicrobial product H2O2, protects the mucosal surface in the small intestine from the cholera pathogen and modifies the composition of the microbiota. DAO is also a determinant of intestinal sIgA levels. Collectively, these results identify D-aa and DAO as previously unrecognized mediators of microbe-host interplay and homeostasis on the epithelial surface of the small intestine. |