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Objectives: Infectious diarrhea, a leading cause of morbidity and deaths, is less prevalent in breastfed infants compared with infants fed infant formula. The dominant human milk oligosaccharide (HMO), α-1,2-fucosyllactose (2'-FL), has structural homology to bacterial adhesion sites in the intestine and may in part explain the protective effects of human milk. We hypothesized that 2'-FL prevents diarrhea via competitive inhibition of pathogen adhesion in a pig model for sensitive newborn infants., Methods: Intestinal cell studies were coupled with studies on cesarean-delivered newborn pigs (n = 24) without (control) or with inoculation of enterotoxigenic Escherichia coli F18 (7.5 × 10/day for 8 days) fed either no (F18) or 10 g/L 2'-FL (2FL-F18)., Results: In vitro studies revealed decreased pathogen adhesion to intestinal epithelial cells with 2'-FL (5 g/L; P < 0.001). F18 pigs showed more diarrhea than control pigs (P < 0.01). Administration of 2'-FL to F18 pigs failed to prevent diarrhea, although the relative weight loss tended to be reduced (-19 vs -124 g/kg, P = 0.12), higher villi were observed in the distal small intestine (P < 0.05), and a trend toward increased proportion of mucosa and activities of some brush border enzymes in the proximal small intestine. In situ abundance of α-1,2-fucose and E coli was similar between groups, whereas sequencing showed higher abundance of Enterobacteriaceae in F18, Enterococcus in control and Lachnospiraceae in 2FL-F18 pigs., Conclusions: 2'-FL inhibited in vitro adhesion of E coli F18 to epithelial cells, but had limited effects on diarrhea and mucosal health in newborn pigs challenged with E coli F18.

Objectives: 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., Methods: 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., Results: 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., Conclusions: 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.