Early infant formula feeding impacts urinary metabolite profile at 3 months of age

Authors: ROSA, FERNANDA - Arkansas Children'S Nutrition Research Center (ACNC); MERCER, KELLY - Arkansas Children'S Nutrition Research Center (ACNC); LIN, HAIXIA - Arkansas Children'S Nutrition Research Center (ACNC); SIMS, CLARK - Arkansas Children'S Nutrition Research Center (ACNC); PACK, LINDSAY - Arkansas Children'S Nutrition Research Center (ACNC); GOOD, GRACE - Arkansas Children'S Nutrition Research Center (ACNC); Badger, Thomas; ANDRES, ALINE - University Arkansas For Medical Sciences (UAMS); YERUVA, LAXMI - University Arkansas For Medical Sciences (UAMS)

Submitted to: Nutrients
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/18/2020
Publication Date: 11/20/2020
Citation: Rosa, F., Mercer, K., Lin, H., Sims, C.R., Pack, L.M., Good, G., Badger, T.M., Andres, A., Yeruva, L. 2020. Early infant formula feeding impacts urinary metabolite profile at 3 months of age. Nutrients. 12(11):3552. https://doi.org/10.3390/nu12113552.
DOI: https://doi.org/10.3390/nu12113552

Interpretive Summary: Exclusive breastfeeding is recommended to newborns during the first 6 months of life by the World Health Organization and American Academy of Pediatrics, however the Center for Disease Control and Prevention (CDC) in 2016 reported that approximately 35% of infants national wide are fed human milk (HM) alternatives, infant formulas from birth to 12 months of age. It has been shown that breastfeeding reduces the mortality rate in preterm babies and decreases the incidence of infections including respiratory tract infections and necrotizing enterocolitis in full term babies. However, the mechanisms involved in health outcomes during neonatal feeding remain to be fully characterized. Also, knowledge of the urinary metabolites profile of infants consuming HM and infant formula is limited. Urine, as a biospecimen is less invasive to collect than blood and offers higher volumes for multiple downstream analyses. Therefore, we evaluated the urine samples from healthy 3 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] and analyzed the metabolite profile upon neonatal diet using untargeted metabolomics approach. Based on discriminant analysis, the main divergence in the metabolic profiling was caused by HM relative to both formula diet groups, while the differences in urinary metabolites between the formula groups were noted. The dietary-specific pattern of urinary metabolites of amino acids and monosaccharides were found in HM-fed infants aged 3 months, which might be linked to the microbial catabolism of proteins and carbohydrates. The SF diet enhanced the excretion of metabolites from polyphenols microbial catabolism. Overall, our findings indicate that urinary metabolites may mirror the infant's metabolism as noninvasive biomarkers and a potential tool to evaluate the impact of infant diets in early life.

Technical 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 3 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 were significantly different among the feeding groups. Dietary-specific pattern of urinary metabolites includes sugars, sugar alcohols, amino acids and polyphenols among the infant diet groups at 3 months of age. 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.