Neonatal Gut and Immune Responses to ß-Casein Enriched Formula in Piglets.

ABSTRACT

BACKGROUND: ß-casein is the main casein constituent in human milk (HM) and a source of bioactive peptides for the developing gastrointestinal tract and immune system. Infant formulas contain less ß-casein than HM, but whether different concentrations of ß-casein affect tolerability and gut and immune maturation in newborns is unknown. OBJECTIVES: Using near-term piglets as a model for newborn infants, we investigated whether increasing the ß-casein fraction in bovine-based formula is clinically safe and may improve gut and immune maturation. METHODS: Three groups of near-term pigs (96% gestation) were fed formula with bovine casein and whey protein (ratio 4060) 1) standard skim milk casein (BCN-standard, 35% ß-casein of total casein, n = 18); 2) ß-casein enrichment to HM concentrations (BCN-medium, 65%, n = 19); and 3) high ß-casein enrichment (BCN-high, 91%, n = 19). A reference group was fed 100% whey protein concentrate (WPC) as protein (WPC, n = 18). Intestinal and immune parameters were assessed before and after euthanasia on day 5. RESULTS: Clinical variables (mortality, activity, body growth, and diarrhea) were similar among the groups, and no differences in intestinal or biochemical parameters were observed between BCN-standard and BCN-medium pigs. However, pigs receiving high amounts of ß-casein (BCN-high) had lower small intestine weight and tended to have more intestinal complications (highest gut pathology score, permeability, and interleukin-8) than the other groups, particularly those receiving no casein (WPC pigs). Blood lymphocyte, thrombocyte, and reticulocyte counts were increased with higher ß-casein, whereas eosinophil counts were reduced. In vitro blood immune cell responses were similar among groups. CONCLUSIONS: ß-casein enrichment of bovine-based formula to HM concentrations is clinically safe, as judged from newborn, near-term pigs, whereas no additional benefits to gut maturation were observed. However, excessive ß-casein supplementation, beyond concentrations in HM, may potentially induce gut inflammation together with increased blood cell populations relative to natural ß-casein concentrations or pure whey-based formula.