AimsWe previously generated Lactococcus lactis-expressed recombinant porcine epidermal growth factor (LL-pEGF), and demonstrated improved growth performance in early-weaned piglets. This study investigates the effect of LL-pEGF on the development and expression of genes that maintain the structural integrity and function of the small intestine in early-weaned piglets. Methods and ResultsThe mitogenic effect of porcine epidermal growth factor (pEGF) was tested invitro with the 5-Bromodeoxyuridine (BrdU) incorporation assay in fibroblast cells. In the invivo study, 40 weaned piglets were randomly allocated to control, antibiotic control, Lc.lactis-expressing empty vector (LL-EV) and LL-pEGF treatment groups. Cells treated with LL-pEGF had higher BrdU-positive stained cells than those in the control and the LL-EV treatments (P<005). Scanning electron microscope and histological examination demonstrated that the small intestinal villi treated with LL-pEGF were higher (P<005) than in the other treatments. LL-pEGF increased the messenger RNA (mRNA) expression levels of the intestinal structural integrity proteins trefoil factor 3, claudin 1 (CLDN1), occludin and zonula occludens 1 (ZO-1), the digestive enzymes sucrose, aminopeptidase A, and aminopeptidase N, and the nutrient transporters sodium/glucose cotransporter 1 (SGLT1), glucose transporter 2, and peptide transporter 1 (PEPT1) as compared with the control (P<005) in the small intestine. Meanwhile, the mRNA levels of CLDN1 in the jejunum and ZO-1 in the ileum were higher in the LL-EV group than in the control group (P<005). LL-EV and the antibiotic control increased SGLT1 mRNA in the jejunum and PEPT1 mRNA in the ileum compared with the control (P<005). ConclusionsRecombinant pEGF promotes cell mitosis. Oral administration of Lc.lactis-expressing pEGF stimulated intestinal development by upregulating the gene expression of the intestinal structural integrity proteins, the digestive enzymes and the nutrient transporters. Significance and Impact of the StudyThe combination of epidermal growth factor and genetically modified micro-organisms may be used as dietary supplements to reduce intestinal stress in animals and even humans.