Bile Acid Administration Elicits an Intestinal Antimicrobial Program and Reduces the Bacterial Burden in Two Mouse Models of Enteric Infection

Abstract

ABSTRACT In addition to their chemical antimicrobial nature, bile acids are thought to have other functions in the homeostatic control of gastrointestinal immunity. However, those functions have remained largely undefined. In this work, we used ileal explants and mouse models of bile acid administration to investigate the role of bile acids in the regulation of the intestinal antimicrobial response. Mice fed on a diet supplemented with 0.1% chenodeoxycholic acid (CDCA) showed an upregulated expression of Paneth cell α-defensins as well as an increased synthesis of the type-C lectins Reg3b and Reg3g by the ileal epithelium. CDCA acted on several epithelial cell types, by a mechanism independent from farnesoid X receptor (FXR) and not involving STAT3 or β-catenin activation. CDCA feeding did not change the relative abundance of major commensal bacterial groups of the ileum, as shown by 16S analyses. However, administration of CDCA increased the expression of ileal Muc2 and induced a change in the composition of the mucosal immune cell repertoire, decreasing the proportion of Ly6G + and CD68 + cells, while increasing the relative amount of IgGκ + B cells. Oral administration of CDCA to mice attenuated infections with the bile-resistant pathogens Salmonella enterica serovar Typhimurium and Citrobacter rodentium , promoting lower systemic colonization and faster bacteria clearance, respectively. Our results demonstrate that bile acid signaling in the ileum triggers an antimicrobial program that can be potentially used as a therapeutic option against intestinal bacterial infections.