Epidermal growth factor containing culture supernatant enhances intestine development of early-weaned pigs in vivo: Potential mechanisms involved

• We previously demonstrated that epidermal growth factor (EGF) containing supernatant, from the culture of a genetically modified EGF expressing Lactococcus lactis, enhance growth performance of early-weaned pigs. The current study aimed to further understand the physiological and molecular mechanisms behind this improved performance.
• The EGF supernatant increased the expression intestine function genes such as glucose cotransporter sodium-glucose linked transporter 1 (SGLT1), and glucagon-like peptide-2 (GLP2), mucin2, goblet cell numbers, and thus intestine development.
• The EGF supernatant suppresses early-weaned associate intestine inflammation as reflected by decreased lamina propria width, and higher expression of anti-inflammatory cytokine, IL-13.

We have previously generated epidermal factor expressing Lactococcus lactis (EGF-LL) using a bioengineering approach, and shown that EGF-LL fermentation supernatant enhanced newly weaned pigs growth. The objective of the current study was to further understand the mechanisms behind this improved performance. Sixty-four piglets were weaned at 3 weeks of age and then fed ad libitum according to a 2-phase feeding program. Four pens with 8 pigs per pen were assigned to each of two treatments for 3 weeks: (1) EGF containing supernatant from EGF-LL culture (SuperEGF) or (2) blank M17GE media (Control). Consistent with previous findings, SuperEGF pigs had an increased average daily gain during week 3 post-weaning (433.4 ± 10.86 vs 388.7 ± 7.76 g; P < 0.05) and overall gain:feed ratio (0.757 ± 0.03 vs 0.677 ± 0.01 kg/kg, P < 0.05). Moreover, jejunal structure development was enhanced, and inflammation index was minimized in SuperEGF pigs as indicated by increased villi height (P < 0.05), decreased lamina propria width (P < 0.05), and higher expression of anti-inflammatory cytokine, IL-13 (P < 0.05). Further, goblet cell numbers and Muc2 levels were increased in SuperEGF pigs. Interestingly, the weaning-induced decrease of glucose cotransporter sodium-glucose linked transporter 1 (SGLT1) and glucagon-like peptide-2 (GLP2) levels was reversed by SuperEGF supplementation. Our findings add to our understanding of the mechanisms behind enhancing piglet performance by EGF containing fermentation product.