Transition from parenteral to enteral nutrition induces immediate diet-dependent gut histological and immunological responses in preterm neonates

Abstract

Necrotizing enterocolitis (NEC) in preterm infants develops very rapidly from a mild intolerance to enteral feeding into intestinal mucosal hemorrhage, inflammation, and necrosis. We hypothesized that immediate feeding-induced gut responses precede later clinical NEC symptoms in preterm pigs. Fifty-six preterm pigs were fed total parenteral nutrition (TPN) for 48 h followed by enteral feeding for 0, 8, 17, or 34 h with either colostrum (Colos, n = 20) or formula (Form, n = 31). Macroscopic NEC lesions were detected in Form pigs throughout the enteral feeding period (20/31, 65%), whereas most Colos pigs remained protected (1/20, 5%). Just 8 h of formula feeding induced histopathological lesions, as evidenced by capillary stasis and necrosis, epithelial degeneration, edema, and mucosal hemorrhage. These immediate formula-induced changes were paralleled by decreased digestive enzyme activities (lactase and dipeptidylpeptidase IV), increased nutrient fermentation, and altered expression of innate immune defense genes such as interleukins (IL-1α, IL-6, IL-18), nitric oxide synthetase, tight junction proteins (claudins), Toll-like receptors (TLR-4), and TNF-α. In contrast, the first hours of colostrum feeding induced no histopathological lesions, increased maltase activity, and induced changes in gene expressions related to tissue development. Total bacterial density was high after 2 days of parenteral feeding and was not significantly affected by diet (colostrum, formula) or length of enteral feeding (8-34 h), except that a few bacterial groups (Clostridium, Enterococcus, Streptococcus species) increased with time. We conclude that a switch from parenteral to enteral nutrition rapidly induces diet-dependent histopathological, functional, and proinflammatory insults to the immature intestine. Great care is required when introducing enteral feeds to TPN-fed preterm infants, particularly when using formula, because early feeding-induced insults may predispose to NEC lesions that are difficult to revert by later dietary or medical interventions.

Spray Dried, Pasteurised Bovine Colostrum Protects Against Gut Dysfunction and Inflammation in Preterm Pigs

“…However, the mucosa regained its hexose absorptive capacity when the pigs subsequently were fed BC products, while the value remained low after continued formula feeding. Contrary to our earlier studies, all pigs in this study were fed a few boluses of formula after the TPN period and this initiates an intestinal inflammatory response, as shown previously (32). It was therefore not surprising that we observed signs of inflammation in all three BC groups and higher NEC score/severity than in preterm pigs transitioned to colostrum products from birth or immediately after the TPN period (6,18,31).…”

Physical activity level is impaired and diet dependent in preterm newborn pigs

“…It is noteworthy in this study that IF remained inferior to BC and HM, even using a relatively slow (27). Furthermore, IF products are clearly inferior to intact milk products in stimulating immunity and mucosal defense mechanisms (28)(29)(30). This study demonstrates that preterm pigs display lower physical activity level relative to term pigs over the first week of life and that a slow increase in enteral nutrition stimulates GIT growth as well as physical activity level.…”

Neonatal piglet survival: impact of sow nutrition around parturition on fetal glycogen deposition and production and composition of colostrum and transient milk

“…Birth is associated with several distinct and coordinated physiological events in both piglets and sows. For piglets, birth marks a sudden decrease in body temperature (Kammersgaard et al, 2011) and the abrupt transition from parenteral (via placenta) to enteral supply of nutrients (Siggers et al, 2011). Consequently, thermoregulation becomes extremely important and it must be met by oxidation of nutrients (Noblet et al, 1997).…”