Early Infant Formula Feeding Impacts Urinary Metabolite Profile at 3 Months of Age

Abstract

There is a growing consensus that nutritional programming may persist and influence risk for several chronic diseases in adulthood. In the present study, we used urinary metabolic analysis in assessing diet effects on early-life metabolism. Urine samples from healthy three-month-old infants fed human milk (HM; n = 93), cow’s milk-based infant formula [MF; n = 80], or soy protein-based infant formula (SF; n = 76) were analyzed with an untargeted metabolomics approach using GC-TOF MS. PLS-DA and ANOVA analyses were performed using MetaboAnalyst (v4.0). A total of 150 metabolites differed significantly among the feeding groups, including dietary-specific patterns of urinary metabolites of sugars, sugar alcohols, amino acids, and polyphenols. Urinary metabolites may mirror the infant’s overall metabolism and serve as a noninvasive tool to examine the neonatal effects of diet on early-infant metabolism.

Metabolic impact of infant formulas in young infants. An outlook from the urine metabolome

“…Our results are in line with previously reported evidence from other metabolomics approaches suggesting energetic metabolism changes between breast-fed and formula-fed infants [ 14 , 17 ]. Although some studies report increased ketogenesis and fat oxidation, our results showed mainly changes in gluconeogenesis.…”

“…In addition, less signals are evident in the area of carbohydrates in the urinary H 1 -NMR profile of this group, which may reflect the less oligosaccharide content of infant formulas since they are made with bovine milk [ 49 ]. Similar results have been reported previously [ 17 , 50 ].…”

“…In general, our results show several differences in the metabolic profiles observed by H 1 -NMR and GC-MS analyses between infants receiving infant formula compared to breast fed infants ( Table 1 , Figure 1 ). In fact, metabolic pathway analysis using the obtained results evidenced changes in urinary excretion patterns of metabolites mainly associated to amino acid metabolism, which may be related to the higher protein content of infant formulas and that coincides with previous studies [ 14 , 17 ] ( Figure 3 ). In addition, effects of formula lipidic and carbohydrate components were also observed.…”

“…In terms of infant formula impact on OA levels in infants, previous studies have reported changes in dicarboxylic acids, ketone bodies, fatty acids, amino acid derivates and phenolic compounds between formula-fed and breast-fed infants [ 14 , 15 , 16 , 17 ]. Such findings have been observed using different samples (urine, plasma, serum, dried blood spots and faeces) and technical approximations including LC-MS, NMR, GC-MS among others [ 15 , 16 ].…”

“…Up to now several studies have been conducted exploring the effect of infant formula based nutrition on newborn intestinal function [7], immunological system development [11], association to allergies and infectious diseases, duration of breastfeeding [12,13], and newborn metabolism [11,[14][15][16][17]. In terms of latter, metabolomics approaches are heterogeneous including targeted and non-targeted [15,16].…”