Mother's own milk is the optimal first diet for preterm infants, but donor human milk (DM) or infant formula (IF) is used when supply is limited. We hypothesized that a gradual introduction of bovine colostrum (BC) or DM improves gut maturation, relative to IF during the first 11 days after preterm birth. Preterm pigs were fed gradually advancing doses of BC, DM, or IF (3–15 ml·kg⁻¹·3 h⁻¹, n = 14–18) before measurements of gut structure, function, microbiology, and immunology. The BC pigs showed higher body growth, intestinal hexose uptake, and transit time and reduced diarrhea and gut permeability, relative to DM and IF pigs ( P < 0.05). Relative to IF pigs, BC pigs also had lower density of mucosa-associated bacteria and of some putative pathogens in colon, together with higher intestinal villi, mucosal mass, brush-border enzyme activities, colonic short chain fatty acid levels, and bacterial diversity and an altered expression of immune-related genes (higher TNFα, IL17; lower IL8, TLR2, TFF, MUC1, MUC2) (all P < 0.05). Values in DM pigs were intermediate. Severe necrotizing enterocolitis (NEC) was observed in >50% of IF pigs, while only subclinical intestinal lesions were evident from DM and BC pigs. BC, and to some degree DM, are superior to preterm IF in stimulating gut maturation and body growth, using a gradual advancement of enteral feeding volume over the first 11 days after preterm birth in piglets. Whether the same is true in preterm infants remains to be tested.

Bioactive milk proteins may be important in protecting preterm infants from developing inflammation and necrotising enterocolitis (NEC). A preterm pig model was used to investigate the protective effects of enteral bovine lactoferrin (bLF) against NEC development and inflammation. Caesarean-delivered preterm pigs were fed parenteral and minimal enteral nutrition for the first 2 d followed by 2 d of total enteral nutrition before euthanasia. Pigs were stratified into two groups and fed with either a control formula (CON,n15) or a 10 g/l of bLF-enriched formula (LF,n13). NEC incidence, gut functions and inflammatory cytokines were analysed. NEC incidence and nutrient absorption were similar between the two groups. In pigs that developed NEC, disease outcome was more severe in the colon accompanied by increased intestinal permeability in LF pigs. In contrary, the LF pigs had a lowered IL-1β level in the proximal small intestine. Dose-dependent effects of bLF on cell proliferation, intracellular signalling and cytokine secretion were tested in porcine intestinal epithelial cells (PsIc1)in vitro.Low doses (0·1–1 g/l) increased cell proliferation via extracellular signal-regulated kinase (ERK), limited IL-8 secretion and prevented NF-κB and hypoxia-inducible factor-1α (HIF-1α) activation, suggesting anti-inflammatory effects. In contrast, at a higher dose (10 g/l), bLF exerted adverse effects by reducing cell proliferation, stimulating IL-8 release, inhibiting ERK activation and up-regulating NF-κB and HIF-1α activation. Overall, at a dose of 10 g/l, bLF exacerbated disease severity in pigs that developed NEC, while thein vitrostudies indicated the positive effects of bLF at low doses (0·1–1 g/l). Supplementation of infant formulas with bLF should therefore be optimised carefully.

Background: Holder pasteurization (HP) destroys multiple bioactive factors in donor human milk (DM), and UV-C irradiation (UVC) is potentially a gent