Oral administration of Lactococcus lactis-expressed recombinant porcine epidermal growth factor stimulates the development and promotes the health of small intestines in early-weaned piglets.

Aims: We 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 Results: The mitogenic effect of porcine epidermal growth factor (pEGF) was tested in vitro with the 5-Bromodeoxyuridine (BrdU) incorporation assay in fibroblast cells. In the in vivo 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 < 0·05). Scanning electron microscope and histological examination demonstrated that the small intestinal villi treated with LL-pEGF were higher (P < 0·05) 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 < 0·05) 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 < 0·05). LL-EV and the antibiotic control increased SGLT1 mRNA in the jejunum and PEPT1 mRNA in the ileum compared with the control (P < 0·05).

Conclusions: Recombinant 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 Study: The 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.