Generation of epidermal growth factor–expressing Lactococcus lactis and its enhancement on intestinal development and growth of early-weaned mice

Abstract

Background: Epidermal growth factor (EGF) plays an important role in intestinal proliferation and differentiation. Previous studies by others have shown that administration of EGF into the ileum lumen enhances intestinal development.Objective: The objective was to examine the feasibility of expressing and delivering EGF via Lactococcus lactis to early-weaned mice to enhance intestinal development at this critical transition stage.Design: EGF-expressing L. lactis (EGF-LL) was generated with a recombinant approach. Early-weaned mice were orally gavaged with the recombinant bacteria. Body weight, mean villous height, and crypt depth in the intestine were measured to examine the influence of EGF-LL on the intestinal development of early-weaned mice in vivo.Results: Populations of EGF-LL were shown to survive throughout the intestinal tract, and the recombinant EGF protein was also detected in intestinal contents. Weight gain was significantly greater in mice that received EGF-LL than in control mice fed phosphate-buffered saline or L. lactis transformed with the empty vector backbone but was comparable with that of the positive control mice that received recombinant human EGF. EGF-LL increased mean villous height and crypt depth in the intestine. Immunohistochemistry also confirmed that enterocyte proliferation was enhanced in mice that received EGF-LL, as evidenced by the greater number of cells stained with proliferative cell nuclear antigen in the intestine.Conclusions: This study showed that EGF-LL had beneficial effects on the intestinal growth of newly weaned mice. The combination of growth factor delivery and a probiotic approach may offer possibilities for formulating dietary supplements for children during their weaning transition stage.