Enteral feeding induces diet-dependent mucosal dysfunction, bacterial proliferation, and necrotizing enterocolitis in preterm pigs on parenteral nutrition.

Preterm neonates have an immature gut and metabolism and may benefit from total parenteral nutrition (TPN) before enteral food is introduced. Conversely, delayed enteral feeding may inhibit gut maturation and sensitize to necrotizing enterocolitis (NEC). Intestinal mass and NEC lesions were first recorded in preterm pigs fed enterally (porcine colostrum, bovine colostrum, or formula for 20-40 h), with or without a preceding 2- to 3-day TPN period (n = 435). Mucosal mass increased during TPN and further after enteral feeding to reach an intestinal mass similar to that in enterally fed pigs without TPN (+60-80% relative to birth). NEC developed only after enteral feeding but more often after a preceding TPN period for both sow's colostrum (26 vs. 5%) and formula (62 vs. 39%, both P < 0.001, n = 43-170). Further studies in 3-day-old TPN pigs fed enterally showed that formula feeding decreased villus height and nutrient digestive capacity and increased luminal lactic acid and NEC lesions, compared with colostrum (bovine or porcine, P < 0.05). Mucosal microbial diversity increased with enteral feeding, and Clostridium perfringens density was related to NEC severity. Formula feeding decreased plasma arginine, citrulline, ornithine, and tissue antioxidants, whereas tissue nitric oxide synthetase and gut permeability increased, relative to colostrum (all P < 0.05). In conclusion, enteral feeding is associated with gut dysfunction, microbial imbalance, and NEC in preterm pigs, especially in pigs fed formula after TPN. Conversely, colostrum milk diets improve gut maturation and NEC resistance in preterm pigs subjected to a few days of TPN after birth.

Formula-feeding reduces lactose digestive capacity in neonatal pigs.

The intestine of newborn pigs develops rapidly during the first days postpartum. We investigated if feeding milk replacer (infant formula) as an alternative to colostrum has compromising effects on nutrient digestive function in the neonatal period. Nineteen piglets born at term were assigned to one of four treatments: (1) newborn controls; (2) natural suckling for 24 h; (3) tube-fed formula for 24 h; (4) tube-fed porcine colostrum for 24 h. All three fed groups showed significant increases in small-intestinal and colonic weights, villous heights and widths, maltase and aminopeptidase A activities, and decreases in dipeptidylpeptidase IV activity, relative to newborn pigs. Following oral boluses of mannitol, lactose or galactose, formula-fed pigs showed significantly reduced plasma levels of mannitol and galactose compared with colostrum-fed pigs. Activity of intestinal inducible NO synthase and plasma levels of cortisol were significantly increased, whereas intestinal constitutive NO synthase and alpha-tocopherol were decreased in formula-fed pigs compared with colostrum-fed pigs. Although formula-fed pigs only showed minor clinical signs of intestinal dysfunction and showed similar intestinal trophic responses just after birth, as those fed colostrum, lactose digestive capacity was markedly reduced. We conclude that formula-feeding may exert detrimental effects on intestinal function in neonates. Formula-induced subclinical malfunction of the gut in pigs born at term was associated with altered NO synthase activity and antioxidative capacity.

Diet- and colonization-dependent intestinal dysfunction predisposes to necrotizing enterocolitis in preterm pigs.

BACKGROUND & AIMS: Preterm birth and formula feeding are key risk factors associated with necrotizing enterocolitis (NEC) in infants, but little is known about intestinal conditions that predispose to disease. Thus, structural, functional, and microbiologic indices were used to investigate the etiology of spontaneous NEC development in preterm pigs. METHODS: Piglets were delivered by cesarean section at 92% gestation, reared in infant incubators, and fed infant formula or colostrum every 3 hours (n = 120) until tissue collection at 1-2 days of age. RESULTS: Clinical and histopathologic signs of NEC were observed in 57% of pigs fed FORMULA (26/46) and in 5% of pigs fed COLOSTRUM (2/38) (P < .05). Relative to COLOSTRUM, both healthy and sick FORMULA pigs had reduced intestinal villous heights, enzyme activities, nutrient absorption, and antioxidant levels and higher inducible nitric oxide synthetase activity (P < .05). In healthy pigs, mucosal microbial diversity remained low and diet independent. NEC pigs showed bacterial overgrowth, and a high mucosal density of Clostridium perfringens was detected in some but not all pigs. Germ-free conditions and antiserum against Clostridium perfringens toxin prevented intestinal dysfunction and NEC in formula-fed pigs, whereas the gut trophic factors, epidermal growth factor, and glucagon-like peptide 2 had limited effects. CONCLUSIONS: A subclinical, formula-induced mucosal atrophy and dysfunction predispose to NEC and bacterial overgrowth. The adverse feeding effects are colonization dependent and may be reduced by factors in colostrum that include antibodies against aggressive toxins such as those of Clostridium perfringens.