Neonatal gut and immune responses to beta-casein enriched formula in piglets

Background β-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 β-casein than HM, but whether different levels of β-casein affect tolerability and gut and immune maturation in newborns is unknown. Objective Using near-term piglets as a model for newborn infants, we investigate whether increasing the β-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 40:60): 1) Standard skim milk casein (BCN-standard, 35% β-casein of total casein, n=18), 2) β-casein enrichment to HM levels (BCN-medium, 65%, n=19), and 3) high β-casein enrichment (BCN-high, 91%, n=19). A reference group was fed 100% whey protein concentrate 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, 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 β-casein (BCN-high) had lower small intestine weight, and tended to have more intestinal complications (highest gut pathology score, permeability, IL-8) than the other groups, particularly those receiving no casein (WPC pigs). Blood lymphocyte, thrombocyte and reticulocyte counts were increased with higher β-casein, while eosinophil counts were reduced. In vitro blood immune cell responses were similar among groups. Conclusions β-casein enrichment of bovine-based formula to HM levels is clinically safe, as judged from newborn, near-term pigs, while no additional benefits to gut maturation were observed. However, excessive β-casein supplementation, beyond levels in HM, may potentially induce gut inflammation together with increased blood cell populations relative to natural β-casein levels or pure whey-based formula.