Dynamic Changes in the Human Milk Metabolome Over 25 Weeks of Lactation

Overview

Journal Front Nutr

Specialty Nutritional Sciences

Date 2022 Aug 1

PMID 35911093

Authors

Katrine Overgaard Poulsen

Fanyu Meng

Elisa Lanfranchi

Jette Feveile Young

Catherine Stanton

C Anthony Ryan

Alan L Kelly

Ulrik Kraemer Sundekilde

Affiliations

Soon will be listed here.

Abstract

Human milk (HM) provides essential nutrition for ensuring optimal infant growth and development postpartum. Metabolomics offers insight into the dynamic composition of HM. Studies have reported the impact of lactation stage, maternal genotype, and gestational age on HM metabolome. However, the majority of the studies have considered changes within the first month of lactation or sampled with large intervals. This leaves a gap in the knowledge of progressing variation in HM composition beyond the first month of lactation. The objective of this study was to investigate whether the HM metabolome from mothers with term deliveries varies beyond 1 month of lactation, during the period in which HM is considered fully mature. Human milk samples ( = 101) from 59 mothers were collected at weeks 1-2, 3-5, 7-9, and 20-25 postpartum and analyzed using H nuclear magnetic resonance spectroscopy. Several metabolites varied over lactation and exhibited dynamic changes between multiple time points. Higher levels of HM oligosaccharides, cis-aconitate, O-phosphocholine, O-acetylcarnitine, gluconate, and citric acid were observed in early lactation, whereas later in lactation, levels of lactose, 3-fucosyllactose, glutamine, glutamate, and short- and medium-chain fatty acids were increased. Notably, we demonstrate that the HM metabolome is dynamic during the period of maturity.

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References

Ozarda Ilcol Y, Ozbek R, Hamurtekin E, Ulus I . Choline status in newborns, infants, children, breast-feeding women, breast-fed infants and human breast milk. J Nutr Biochem. 2005; 16(8):489-99. DOI: 10.1016/j.jnutbio.2005.01.011. View

Schooneman M, Vaz F, Houten S, Soeters M . Acylcarnitines: reflecting or inflicting insulin resistance?. Diabetes. 2012; 62(1):1-8. PMC: 3526046. DOI: 10.2337/db12-0466. View

Sundekilde U, Downey E, OMahony J, OShea C, Ryan C, Kelly A . The Effect of Gestational and Lactational Age on the Human Milk Metabolome. Nutrients. 2016; 8(5). PMC: 4882716. DOI: 10.3390/nu8050304. View

Alexandre-Gouabau M, Moyon T, David-Sochard A, Fenaille F, Cholet S, Royer A . Comprehensive Preterm Breast Milk Metabotype Associated with Optimal Infant Early Growth Pattern. Nutrients. 2019; 11(3). PMC: 6470768. DOI: 10.3390/nu11030528. View

Sun H, Shi K, Wu X, Xue M, Wei Z, Liu J . Lactation-related metabolic mechanism investigated based on mammary gland metabolomics and 4 biofluids' metabolomics relationships in dairy cows. BMC Genomics. 2017; 18(1):936. PMC: 5712200. DOI: 10.1186/s12864-017-4314-1. View

Bode L . Human milk oligosaccharides: every baby needs a sugar mama. Glycobiology. 2012; 22(9):1147-62. PMC: 3406618. DOI: 10.1093/glycob/cws074. View

Patel D, Witt S . Ethanolamine and Phosphatidylethanolamine: Partners in Health and Disease. Oxid Med Cell Longev. 2017; 2017:4829180. PMC: 5529665. DOI: 10.1155/2017/4829180. View

Wu J, Domellof M, Zivkovic A, Larsson G, Ohman A, Nording M . NMR-based metabolite profiling of human milk: A pilot study of methods for investigating compositional changes during lactation. Biochem Biophys Res Commun. 2015; 469(3):626-32. DOI: 10.1016/j.bbrc.2015.11.114. View

Siziba L, Mank M, Stahl B, Gonsalves J, Blijenberg B, Rothenbacher D . Human Milk Oligosaccharide Profiles over 12 Months of Lactation: The Ulm SPATZ Health Study. Nutrients. 2021; 13(6). PMC: 8228739. DOI: 10.3390/nu13061973. View

10.

Gomez-Gallego C, Morales J, Monleon D, du Toit E, Kumar H, Linderborg K . Human Breast Milk NMR Metabolomic Profile across Specific Geographical Locations and Its Association with the Milk Microbiota. Nutrients. 2018; 10(10). PMC: 6213536. DOI: 10.3390/nu10101355. View

11.

van Sadelhoff J, van de Heijning B, Stahl B, Amodio S, Rings E, Mearin M . Longitudinal Variation of Amino Acid Levels in Human Milk and Their Associations with Infant Gender. Nutrients. 2018; 10(9). PMC: 6163519. DOI: 10.3390/nu10091233. View

12.

Cesare Marincola F, Dessi A, Corbu S, Reali A, Fanos V . Clinical impact of human breast milk metabolomics. Clin Chim Acta. 2015; 451(Pt A):103-6. DOI: 10.1016/j.cca.2015.02.021. View

13.

Dessi A, Briana D, Corbu S, Gavrili S, Cesare Marincola F, Georgantzi S . Metabolomics of Breast Milk: The Importance of Phenotypes. Metabolites. 2018; 8(4). PMC: 6315662. DOI: 10.3390/metabo8040079. View

14.

Turner M, Reynolds C, McMahon L, OMalley E, OConnell M, Sheehan S . Caesarean section rates in women in the Republic of Ireland who chose to attend their obstetrician privately: a retrospective observational study. BMC Pregnancy Childbirth. 2020; 20(1):548. PMC: 7504647. DOI: 10.1186/s12884-020-03199-x. View

15.

Meng X, Dunsmore G, Koleva P, Elloumi Y, Wu R, Sutton R . The Profile of Human Milk Metabolome, Cytokines, and Antibodies in Inflammatory Bowel Diseases Versus Healthy Mothers, and Potential Impact on the Newborn. J Crohns Colitis. 2018; 13(4):431-441. PMC: 6441305. DOI: 10.1093/ecco-jcc/jjy186. View

16.

Ojo-Okunola A, Cacciatore S, Nicol M, du Toit E . The Determinants of the Human Milk Metabolome and Its Role in Infant Health. Metabolites. 2020; 10(2). PMC: 7074355. DOI: 10.3390/metabo10020077. View

17.

Garwolinska D, Hewelt-Belka W, Kot-Wasik A, Sundekilde U . Nuclear Magnetic Resonance Metabolomics Reveals Qualitative and Quantitative Differences in the Composition of Human Breast Milk and Milk Formulas. Nutrients. 2020; 12(4). PMC: 7230615. DOI: 10.3390/nu12040921. View

18.

Zhang S, Zeng X, Ren M, Mao X, Qiao S . Novel metabolic and physiological functions of branched chain amino acids: a review. J Anim Sci Biotechnol. 2017; 8:10. PMC: 5260006. DOI: 10.1186/s40104-016-0139-z. View

19.

Gay M, Koleva P, Slupsky C, du Toit E, Eggesbo M, Johnson C . Worldwide Variation in Human Milk Metabolome: Indicators of Breast Physiology and Maternal Lifestyle?. Nutrients. 2018; 10(9). PMC: 6163258. DOI: 10.3390/nu10091151. View

20.

Dai X, Yuan T, Zhang X, Zhou Q, Bi H, Yu R . Short-chain fatty acid (SCFA) and medium-chain fatty acid (MCFA) concentrations in human milk consumed by infants born at different gestational ages and the variations in concentration during lactation stages. Food Funct. 2020; 11(2):1869-1880. DOI: 10.1039/c9fo02595b. View