OBJECTIVE:: Preterm infants often show intolerance to the first enteral feeds, and the structural and functional basis of this intolerance remains unclear. We hypothesized that preterm and term neonates show similar gut trophic responses to feeding, but different expression of intestinal functional proteins, thus helping to explain why preterm neonates are more susceptible to feeding-induced disorders such as necrotizing enterocolitis (NEC). METHODS:: Incidence of feeding-induced NEC, intestinal mass and brush-border enzyme activities, and the intestinal proteome in preterm caesarean-delivered pigs were compared with the corresponding values in pigs delivered spontaneously at term. RESULTS:: For both preterm and term pigs, mucosal mass and maltase activity increased (+50-100%), while lactase decreased (-50%), relative to values at birth. Only preterm pigs were highly NEC-sensitive (30 vs. 0% in term pigs, P¿