Evidence for human milk as a biological system and recommendations for study design—a report from breastmilk ecology and the genesis of infant nutrition (BEGIN) working group 4

Authors: DONOVAN, SHARON - University Of Illinois; AGHAEEPOU, NIMA - Stanford University School Of Medicine; ANDRES, ALINE - Arkansas Children'S Nutrition Research Center (ACNC); AZAD, MEGHAN - University Of Manitoba; BECKER, MARTIN - Stanford University School Of Medicine; CARLSON, SUSAN - University Of Kansas Medical School; JARVINEN, KIRSI - University Of Rochester; LIN, WEILI - University Of North Carolina; LÖNNERDAL, BO - University Of California, Davis; SLUPSKY, CAROLYN - University Of California, Davis; STEIBER, ALISON - Academy Of Nutrition And Dietetics; RAITEN, DANIEL - National Institutes Of Health (NIH)

Submitted to: The American Journal of Clinical Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/8/2022
Publication Date: 12/8/2023
Citation: Donovan, S., Aghaeepou, N., Andres, A., Azad, M.B., Becker, M., Carlson, S.E., Jarvinen, K.M., Lin, W., Lönnerdal, B., Slupsky, C.M., Steiber, A.L., Raiten, D.J. 2023. Evidence for human milk as a biological system and recommendations for study design—a report from breastmilk ecology and the genesis of infant nutrition (BEGIN) working group 4. The American Journal of Clinical Nutrition. 117(1):S61-S86. https://doi.org/10.1016/j.ajcnut.2022.12.021.
DOI: https://doi.org/10.1016/j.ajcnut.2022.12.021

Interpretive Summary: Human milk contains all of the essential nutrients required by the infant and is a source of bioactive components, living cells and microbes that facilitate the transition to life outside the womb. Designing and interpreting studies to address its complexity depends on the availability of new tools and technologies. Past efforts have often compared human milk to infant formula, which has provided some insight. However, this experimental approach cannot capture the contributions of the individual components to the human milk as a whole or the interaction between these components within the human milk. This paper presents approaches to explore human milk as a biological system and the functional implications of that system and its components.

Technical Abstract: Human milk (HM) contains all of the essential nutrients required by the infant within a complex matrix that enhances the bioavailability of many of those nutrients. In addition, HM is a source of bioactive components, living cells and microbes that facilitate the transition to life outside the womb. Our ability to fully appreciate the importance of this matrix relies on the recognition of short- and long-term health benefits and, as highlighted in previous sections of this supplement, its ecology (i.e., interactions among the lactating parent and breastfed infant as well as within the context of the HM matrix itself). Designing and interpreting studies to address this complexity depends on the availability of new tools and technologies that account for such complexity. Past efforts have often compared HM to infant formula, which has provided some insight into the bioactivity of HM, as a whole, or of individual milk components supplemented to formula. However, this experimental approach cannot capture the contributions of the individual components to the HM ecology, the interaction between these components within the HM matrix, or the significance of the matrix itself to enhance HM bioactivity on outcomes of interest. This paper presents approaches to explore HM as a biological system and the functional implications of that system and its components. Specifically, we discuss study design and data collection considerations, and how emerging analytical technologies, bioinformatics, and systems biology approaches could be applied to advance our understanding of this critical aspect of human biology.