The major cause of newborn intestinal failure is still short bowel syndrome (SBS). Milk fat globule epidermal growth factor-8 (MFG-E8), which is found in human milk, is related to epidermal growth factor (EGF), which is known to improve adaptability in SBS. The role of oral MFG-E8 therapy in newborn pigs with SBS was investigated in this pilot research. Piglets were subjected to a 75% intestine resection, either distal or proximal. Piglets were randomly assigned to receive either MFG-E8 or saline intragastrically, and they were kept on parenteral and enteral feeding for 7 days. Intestinal length and weight, histology, fecal fat analysis, and RT-qPCR analysis of mucosal transcripts, including growth factors, were used to measure adaptation. JI piglets exhibited intestinal lengthening, which was 2-fold larger in the ileum than in the jejunum, while MFG-E8 therapy enhanced lengthening. Regardless of therapy, JC piglets did not show jejunal lengthening. Fat absorption was higher in JI pigs, regardless of treatment. Egf expression was elevated in the ileum of JI pigs, while MFG-E8 therapy enhanced Egfr expression.

Only with JI anatomy did MF-EG8 show site-specific trophic effects. Except for rare patients with residual ileum, this may restrict the treatment’s usefulness for SBS. However, the mechanisms behind these site-specific effects, as well as the function of MFG-E8 in newborn gut development and illnesses such as necrotizing enterocolitis, which often target the ileum, need additional investigation.