TY - JOUR

T1 - A Gently Processed Skim Milk-Derived Whey Protein Concentrate for Infant Formula

T2 - Effects on Gut Development and Immunity in Preterm Pigs

AU - Aasmul-Olsen, Karoline

AU - Akıllıoğlu, Halise Gül

AU - Christiansen, Line Iadsatian

AU - Engholm-Keller, Kasper

AU - Brunse, Anders

AU - Stefanova, Denitsa Vladimirova

AU - Bjørnshave, Ann

AU - Bechshøft, Mie Rostved

AU - Skovgaard, Kerstin

AU - Thymann, Thomas

AU - Sangild, Per Torp

AU - Lund, Marianne Nissen

AU - Bering, Stine Brandt

N1 - Publisher Copyright: © 2024 The Authors. Molecular Nutrition & Food Research published by Wiley-VCH GmbH.

PY - 2024

Y1 - 2024

N2 - Scope: Processing of whey protein concentrate (WPC) for infant formulas may induce protein modifications with severe consequences for preterm newborn development. The study investigates how conventional WPC and a gently processed skim milk-derived WPC (SPC) affect gut and immune development after birth. Methods and results: Newborn, preterm pigs used as a model of preterm infants were fed formula containing WPC, SPC, extra heat-treated SPC (HT-SPC), or stored HT-SPC (HTS-SPC) for 5 days. SPC contained no protein aggregates and more native lactoferrin, and despite higher Maillard reaction product (MRP) formation, the clinical response and most gut and immune parameters are similar to WPC pigs. SPC feeding negatively impacts intestinal MRP accumulation, mucosa, and bacterial diversity. In contrast, circulating T-cells are decreased and oxidative stress- and inflammation-related genes are upregulated in WPC pigs. Protein aggregation and MRP formation increase in HTS-SPC, leading to reduced antibacterial activity, lactase/maltase ratio, circulating neutrophils, and cytotoxic T-cells besides increased gut MRP accumulation and expression of TNFAIP3. Conclusion: The gently processed SPC has more native protein, but higher MRP levels than WPC, resulting in similar tolerability but subclinical adverse gut effects in preterm pigs. Additional heat treatment and storage further induce MRP formation, gut inflammation, and intestinal mucosal damage.

AB - Scope: Processing of whey protein concentrate (WPC) for infant formulas may induce protein modifications with severe consequences for preterm newborn development. The study investigates how conventional WPC and a gently processed skim milk-derived WPC (SPC) affect gut and immune development after birth. Methods and results: Newborn, preterm pigs used as a model of preterm infants were fed formula containing WPC, SPC, extra heat-treated SPC (HT-SPC), or stored HT-SPC (HTS-SPC) for 5 days. SPC contained no protein aggregates and more native lactoferrin, and despite higher Maillard reaction product (MRP) formation, the clinical response and most gut and immune parameters are similar to WPC pigs. SPC feeding negatively impacts intestinal MRP accumulation, mucosa, and bacterial diversity. In contrast, circulating T-cells are decreased and oxidative stress- and inflammation-related genes are upregulated in WPC pigs. Protein aggregation and MRP formation increase in HTS-SPC, leading to reduced antibacterial activity, lactase/maltase ratio, circulating neutrophils, and cytotoxic T-cells besides increased gut MRP accumulation and expression of TNFAIP3. Conclusion: The gently processed SPC has more native protein, but higher MRP levels than WPC, resulting in similar tolerability but subclinical adverse gut effects in preterm pigs. Additional heat treatment and storage further induce MRP formation, gut inflammation, and intestinal mucosal damage.

KW - bioactive whey protein

KW - gut maturation

KW - infant formula

KW - Maillard reaction products

KW - preterm neonates

U2 - 10.1002/mnfr.202300458

DO - 10.1002/mnfr.202300458

M3 - Journal article

C2 - 38389157

AN - SCOPUS:85185475168

VL - 68

JO - Molecular Nutrition and Food Research

JF - Molecular Nutrition and Food Research

SN - 1613-4125

IS - 6

M1 - 2300458

ER -