Preterm Birth Reduces Nutrient Absorption With Limited Effect on Immune Gene Expression and Gut Colonization in Pigs.

Abstract

The primary risk factors for necrotizing enterocolitis (NEC) are preterm birth, enteral feeding, and gut colonization. It is unclear whether feeding and colonization induce excessive expression of immune genes that lead to NEC. Using a pig model, we hypothesized that reduced gestational age would upregulate immune-related genes and cause bacterial imbalance after birth. Preterm (85%-92% gestation, n = 53) and near-term (95%-99% gestation, n = 69) pigs were delivered by cesarean section and euthanized at birth or after 2 days of infant formula or bovine colostrum feeding. At birth, preterm delivery reduced 5 of 30 intestinal genes related to nutrient absorption and innate immunity, relative to near-term pigs, whereas 2 genes were upregulated. Preterm birth also reduced ex vivo intestinal glucose and leucine uptake (40%-50%), but failed to increase cytokine secretions from intestinal explants relative to near-term birth. After 2 days of formula feeding, NEC incidence was increased in preterm versus near-term pigs (47% vs 0%-13%). A total of 6 of the 30 genes related to immunity (TLR2, IL1B, and IL8), permeability (CLDN3, and OCLN), and absorption (SGLT) decreased in preterm pigs without affecting Gram-negative bacteria-related responses (TLR4, IKBA, NFkB1, TNFAIP3, and PAFA). Bacterial abundance tended to be higher in preterm versus near-term pigs (P = 0.09), whereas the composition was unaffected. Preterm birth predisposes to NEC and reduces nutrient absorption but does not induce upregulation of immune-related genes or cause bacterial dyscolonization in the neonatal period. Excessive inflammation and bacterial overgrowth may occur relatively late in NEC progression in preterm neonates.