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Am J Clin Nutr 89: 871-879, 2009. First published January 28, 2009; doi:10.3945/ajcn.2008.27073
American Journal of Clinical Nutrition, doi:10.3945/ajcn.2008.27073
Vol. 89, No. 3, 871-879, March 2009

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© 2009 American Society for Clinical Nutrition

ORIGINAL RESEARCH COMMUNICATION

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

Queenie CK Cheung1,2,3, Zongfei Yuan1,2,3, Paul W Dyce1,2,3, De Wu1,2,3, Kees DeLange1,2,3 and Julang Li1,2,3

1 From the Department of Animal and Poultry Science, University of Guelph, Guelph, Canada (QCKC, ZY, PWD, KD, and JL), and the Institute of Animal Nutrition, Sichuan Agricultural University, Ya-an, China (DW).

2 Supported by Ontario Pork, Natural Sciences and Engineering Research Council, and Agriculture and Agri-Food Canada. QCKC was the recipient of the Vitamin Doctoral Research Scholarship provided by the University of Guelph.

3 Reprints not available. Address correspondence to J Li, Department of Animal and Poultry Science, University of Guelph, Guelph N1G 2W1, Ontario, Canada. E-mail: jli{at}uoguelph.ca.

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.




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