P079 NEONATAL SUPPLEMENTATION OF A LACTOBACILLUS RHAMNOSUS GG (LGG)-DERIVED PROTEIN, P40, PROMOTES INTESTINAL DEVELOPMENT AND PREVENTS COLITIS IN ADULTHOOD

Abstract

p40 transactivates EGF receptor in intestinal epithelial cells, leading to protection of intestinal epithelial cells under the inflammatory condition. This study aimed to determine the effects of neonatal supplementation of p40 on intestinal development and its long-term outcomes. We generated pectin/zein hydrogels for specifically delivering p40 to the small intestine and the colon. Wt, Egfrfl/fl-Vil-Cre with constitutive EGF receptor deletion in the intestinal epithelial cells, and Egfr fl/fl (littermate control) pups were gavaged with p40-containing hydrogels at 0.25, 0.5, and 0.75 μg/day during postnatal days 2-6, 7-13, and 14-21, respectively. Six- to seven-week old mice were treated with DSS and TNBS to induce colitis. The intestinal tissues were prepared for immunostaining and real-time PCR analysis. The fecal IgA level was examined using ELISA. Compared to wt mice receiving hydrogels without p40, treatment with p40-containing hydrogels significantly enhanced bodyweight gain and functional maturation of the intestine, including epithelial cell proliferation and differentiation examined by increasing numbers and gene expression levels of Ki67, and Muc2 and sucrose-isomaltase, respectively, tight junction formation by ZO-1 apical localization and claudin 3 expression prior to weaning, and increased persistent IgA production from early life to adulthood. These p40-induced effects were observed in Egfrfl/fl, but abolished in Egfrfl/fl-Vil-Cre mice. Neonatal p40 treatment decreased inflammatory score and production of proinflammatory cytokines (TNF and IFN-γ in TNBS and TNF, KC, IL-6 in DSS models) in adult mice. These findings reveal novel roles of neonatal supplementation of probiotic-derived factors in promoting EGF receptor-mediated maturation of intestinal functions and innate immunity, which likely promote long-term beneficial outcomes for reducing the susceptibility to intestinal injury and colitis in adulthood.