Effects of Skim Milk Whey-Derived Proteins on Plasma, Urine, and Gut Metabolites in Preterm Piglets as a Model for Infants

ABSTRACT This study investigates the metabolic impact of skim milk whey-derived protein concentrate (SPC) for infant formula, including its heat-treated (HT-SPC) and stored (HTS-SPC) variants, on the plasma, urine, and gut metabolites of newborn piglets, compared to conventional whey protein concentrate (WPC). Preterm piglets were fed formula containing WPC, SPC, HT-SPC, or HT-SPC, HTS-SPC for 5 days. Metabolomic analysis of plasma, urine, and colon content was performed using 1H NMR. Relative to WPC, SPC mainly affected colon content metabolites, increasing 19 metabolites in the colon and tyrosine in plasma, while decreasing pyruvate in colon content and glycine in plasma. Heat-treatment and storage of SPC led to increased metabolite concentrations in colon contents and urine. Notably, significant correlations between gut metabolites and abundant gut bacteria genes were observed only in the SPC-fed pigs. SPC induced higher branched chain amino acid concentrations in the gut, but had minimal effects on plasma and urinary metabolites, likely due to differences in dietary proteins and in microbiota metabolism. While the clinical effects of SPC-induced gut branched chain amino acids remain unclear, the results from our study suggest that SPC-based infant formula is metabolically safe for sensitive newborns, comparable to WPC-based formulas.