title: NMR-based metabolite profiling of human milk: A pilot study of methods for investigating compositional changes during lactation.
abstract: Low-molecular-weight metabolites in human milk are gaining increasing interest in studies of infant nutrition. In the present study, the milk metabolome from a single mother was explored at different stages of lactation. Metabolites were extracted from sample aliquots using either methanol/water (MeOH/H2O) extraction or ultrafiltration. Nuclear magnetic resonance (NMR) spectroscopy was used for metabolite identification and quantification, and multi- and univariate statistical data analyses were used to detect changes over time of lactation. Compared to MeOH/H2O extraction, ultrafiltration more efficiently reduced the interference from lipid and protein resonances, thereby enabling the identification and quantification of 36 metabolites. The human milk metabolomes at the early (9-24 days after delivery) and late (31-87 days after delivery) stages of lactation were distinctly different according to multi- and univariate statistics. The late lactation stage was characterized by significantly elevated concentrations of lactose, choline, alanine, glutamate, and glutamine, as well as by reduced levels of citrate, phosphocholine, glycerophosphocholine, and N-acetylglucosamine. Our results indicate that there are significant compositional changes of the human milk metabolome also in different phases of the matured lactation stage. These findings complement temporal studies on the colostrum and transitional metabolome in providing a better understanding of the nutritional variations received by an infant.
authors.affiliation: Department of Chemistry, Umeå University, Sweden.
authors.forename: Junfang
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Clinical Sciences, Pediatrics, Umeå University, Sweden.
authors.forename: Magnus
authors.initials: M
authors.lastname: Domellöf
authors.affiliation: Foods for Health Institute, University of California, Davis, CA, USA; Department of Nutrition, University of California, Davis, CA, USA.
authors.forename: Angela M
authors.initials: AM
authors.lastname: Zivkovic
authors.affiliation: Department of Medical Biochemistry and Biophysics, Unit of Research, Education and Development-Östersund, Umeå University, Sweden.
authors.forename: Göran
authors.initials: G
authors.lastname: Larsson
authors.affiliation: Department of Pharmacology and Clinical Neuroscience, Umeå University, Sweden. Electronic address: anders.ohman01@umu.se.
authors.forename: Anders
authors.initials: A
authors.lastname: Öhman
authors.affiliation: Department of Chemistry, Umeå University, Sweden. Electronic address: malin.nording@umu.se.
authors.forename: Malin L
authors.initials: ML
authors.lastname: Nording
mesh_terms: D000328:Adult; D005260:Female; D005504:Food Analysis / Q000379:methods; D006801:Humans; D007774:Lactation / Q000502:physiology*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D055442:Metabolome / Q000502:physiology*; D008895:Milk, Human / Q000378:metabolism*; D010865:Pilot Projects; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014462:Ultrafiltration / Q000379:methods
keywords: Human milk; Lactation; Metabolomics; Metabonomics; NMR