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Title: Alpha-lactalbumin enriched whey protein concentrate to improve gut, immunity and brain development in preterm pigs

item NIELSEN, CHARLOTTE - University Of Copenhagen
item HUI, YAN - University Of Copenhagen
item NGUYEN, DUC - University Of Copenhagen
item AHNFELDT, AGNETHE - University Of Copenhagen
item Burrin, Douglas - Doug
item HARTMANN, BOLETTE - University Of Copenhagen
item HECKMANN, ANNE - Arla Foods Ingredients Group P/s
item SANGILD, PER - University Of Copenhagen
item THYMANN, THOMAS - University Of Copenhagen
item BERINF, STINE - University Of Copenhagen

Submitted to: Nutrients
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/14/2020
Publication Date: 1/17/2020
Citation: Nielsen, C., Hui, Y., Nguyen, D., Ahnfeldt, A., Burrin, D.G., Hartmann, B., Heckmann, A., Sangild, P., Thymann, T., Berinf, S. 2020. Alpha-lactalbumin enriched whey protein concentrate to improve gut, immunity and brain development in preterm pigs. Nutrients. 12(1):245.

Interpretive Summary: Premature birth is a worldwide problem and leads to growth failure and neurodevelopmental delay in children. The underlying reason for poor growth in premature infants is poorly understood. There is continued interest in developing infant formulas for premature infants that are optimized to match the nutrient profile of human breast milk. Alpha-lactalbumin is a dominant protein component in human breast milk, but is relative lower in bovine milk. Alpha-lactalbumin is also a rich source of tryptophan, an essential amino acid necessary for protein synthesis and production of neurotransmitters, like serotonin. The aim of this study was to use premature piglets as a model for human premature infants, to test whether feeding a bovine milk-based formula enrich with different amounts of supplemental alpha-lactalbumin would improve growth and neurodevelopment. The results show that feeding bovine-based formulas enrich with alpha-lactalbumin for 19 days were well tolerated but had limited effects on multiple endpoints of growth, organ development, gut function, and brain development and behavior. The results suggest that supplementing bovine milk-based formulas with alpha-lactalbumin for premature infants may be safe and well tolerated.

Technical Abstract: Human milk is rich in nutritional factors, such as alpha-lactalbumin (a-Lac), and important for neonatal development, but nutrient supplementation may be required for optimal growth. Using a pig model, we hypothesized that a-Lac-enriched whey protein concentrate (WPC) supplementation improves neonatal development. Cesarean-delivered preterm pigs were fed either dilute bovine milk (REF) or REF milk supplemented with WPC with normal (STANDARD-ALPHA) or high (HIGH-ALPHA) a-Lac. Clinical, gut, immune and cognitive endpoints (open field, T-maze) were assessed and tissues collected at Day 19. The growth of STANDARD-ALPHA and HIGH-ALPHA were higher than REF (31 vs. 19 g/kg/d). Most organ weights, gut, immunity and brain variables were similar between WPC groups. HIGH-ALPHA had a higher bone mineral content, colon microbial diversity and an abundance of specific bacteria and microbial metabolites, and tended to show a faster food transit time (p=0.07). Relative to REF, WPC pigs showed higher relative organ weights, blood amino acids, blood neutrophil function, and microbial metabolites, but lower brush-border enzyme activities and plasma cortisol. Cognition outcomes did not differ among the groups. In conclusion, WPC supplementation of milk improved some growth, gut and immunity parameters in preterm pigs. However, increasing the a-Lac content beyond human milk levels had limited effects on the immature gut and developing brain.