Maternal adiposity alters the human milk metabolome: Associations between non-glucose monosaccharides and infant adiposity

Authors: SABEN, JESSICA - University Arkansas For Medical Sciences (UAMS); SIMS, CLARK - Arkansas Children'S Nutrition Research Center (ACNC); PICCOLO, BRIAN - Arkansas Children'S Nutrition Research Center (ACNC); ANDRES, ALINE - Arkansas Children'S Nutrition Research Center (ACNC)

Submitted to: The American Journal of Clinical Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/6/2020
Publication Date: 8/25/2020
Citation: Saben, J.L., Sims, C.R., Piccolo, B.D., Andres, A. 2020. Maternal adiposity alters the human milk metabolome: Associations between non-glucose monosaccharides and infant adiposity. American Journal of Clinical Nutrition. 112(5):1228-1239. https://doi.org/10.1093/ajcn/nqaa216.
DOI: https://doi.org/10.1093/ajcn/nqaa216

Interpretive Summary: The association between small components of human milk, known as metabolites, and outcomes for infants has not been thoroughly investigated. The objective of this study was to measure any differences in human milk metabolites due to maternal obesity and to determine if any individual metabolites are associated with infant obesity during the first 6 months of life. Maternal were assessed before week 14 of pregnancy. Human milk samples were collected at age 0.5 months (159 mother-child pairs), 2 months (131 mother-child pairs), and 6 months (94 mother-child pairs) from normal weight and obese mothers. Modeling identify 23, 17, and 10 metabolites that described maternal adiposity indices at age 0.5, 2, and 6 months, respectively. Monosaccharides and sugar alcohols were the most representative annotated metabolite classes that were increased in milk of obese women. Mannose, lyxitol, and shikimic acid predicted higher infant adiposity over the first 6 months of life. This study reports on one of the largest groups to date examining the metabolic profiles in human milk comparing normal weight and obese women. Maternal obesity was associated with increased amounts of milk non-glucose monosaccharides. Human milk metabolomics may be useful in predicting infant adiposity.

Technical Abstract: Human milk composition is altered by maternal obesity. The association between milk metabolites and infant outcomes has not been thoroughly investigated. This study aimed to quantify maternal adiposity-related differences in the human milk metabolome and to identify metabolites associated with infant adiposity during the first 6 months postpartum using untargeted metabolomics. Maternal anthropometrics were assessed <= week 14 of gestation. Human milk samples were collected at 0.5 months (0.5M; n=159), 2 months (2M; n=131), and 6 months (6M; n=94) postpartum from normal weight (NW, BMI=18.5 – 24.9 kg/m2) and obese (OB, BMI>30 kg/m2) mothers. Gas chromatography time-of-flight-mass spectrometry was used to identify metabolic signatures that discriminate NW and OB women. Partial least squared (PLS)-discriminant analysis, and PLS-regression models were assessed to examine relationships between metabolites and maternal BMI and fat mass. Metabolites altered by maternal obesity were used in linear mixed effect models to predict infant adiposity. Multivariate modeling identified 23, 17, and 10 metabolites that described maternal adiposity indices at 0.5M, 2M, and 6M postpartum, respectively. Monosaccharides and sugar alcohols were the most representative annotated metabolite classes that were increased in milk from OB women and included: mannose, ribose, lyxose, lyxitol (0.5M); mannose, ribitol, glycerol, isothreonic acid, lyxitol (2M); lyxitol and isothreonic acid (6M). Other discriminant metabolites included: 1-monostearin, xylonolactone, shikimic acid, pseudouridine, and dodecanol (0.5M); N-acetyl-D-hexosamine, fumaric acid (2M); uric acid, and tyrosine (6M). Mannose, lyxitol, and shikimic acid predicted higher infant adiposity over the first 6 months of life. This study reports on one of the largest cohorts to date examining the metabolic profiles in human milk comparing NW and OB women. Maternal adiposity was associated with increased amounts of milk non-glucose monosaccharides. Human milk metabolomics may be useful in predicting infant adiposity.