An equitable, community-engaged translational framework for science in human lactation and infant feeding—a report from “Breastmilk Ecology: Genesis of Infant Nutrition (BEGIN)” Working Group 5
“…Recently, the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) of the National Institutes of Health (NIH) initiated the “Breastmilk Ecology: Genesis of Infant Nutrition (BEGIN)” Project ( Raiten et al, 2023 ), which convened leaders in the field of lactation science to “explore factors influencing the synthesis, composition, and best use of human milk.” The BEGIN working groups conceptualized new approaches toward understanding human milk as a complex biological system ( Donovan et al, 2023 ; Krebs et al, 2023 ; Neville et al, 2023 ; Nommsen-Rivers et al, 2023 ; Smilowitz et al, 2023 ). Indeed, milk fat secretion is thought to be influenced by myriad factors within the context of the mother-milk-infant triad.…”
Introduction: Human milk delivers critical nutritional and immunological support to human infants. Milk fat globules (MFGs) and their associated membranes (MFGMs) contain the majority of milk lipids and many bioactive components that contribute to neonatal development and health, yet their compositions have not been fully defined, and the mechanisms responsible for formation of these structures remain incompletely understood.Methods: In this study, we used untargeted mass spectrometry to quantitatively profile the protein compositions of freshly obtained MFGs and their paired, physically separated MFGM fractions from 13 human milk samples. We also quantitatively profiled the MFG protein compositions of 9 pooled milk samples from 18 lactating mouse dams.Results: We identified 2,453 proteins and 2,795 proteins in the majority of human MFG and MFGM samples, respectively, and 1,577 proteins in mouse MFGs. Using paired analyses of protein abundance in MFGMs compared to MFGs (MFGM-MFG; 1% FDR), we identified 699 proteins that were more highly abundant in MFGMs (MFGM-enriched), and 201 proteins that were less abundant in MFGMs (cytoplasmic). MFGM-enriched proteins comprised membrane systems (apical plasma membrane and multiple vesicular membranes) hypothesized to be responsible for lipid and protein secretion and components of membrane transport and signaling systems. Cytoplasmic proteins included ribosomal and proteasomal systems. Comparing abundance between human and mouse MFGs, we found a positive correlation (R2 = 0.44, p < 0.0001) in the relative abundances of 1,279 proteins that were found in common across species.Discussion: Comparative pathway enrichment analyses between human and mouse samples reveal similarities in membrane trafficking and signaling pathways involved in milk fat secretion and identify potentially novel immunological components of MFGs. Our results advance knowledge of the composition and relative quantities of proteins in human and mouse MFGs in greater detail, provide a quantitative profile of specifically enriched human MFGM proteins, and identify core cellular systems involved in milk lipid secretion.
“…Recently, the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) of the National Institutes of Health (NIH) initiated the “Breastmilk Ecology: Genesis of Infant Nutrition (BEGIN)” Project ( Raiten et al, 2023 ), which convened leaders in the field of lactation science to “explore factors influencing the synthesis, composition, and best use of human milk.” The BEGIN working groups conceptualized new approaches toward understanding human milk as a complex biological system ( Donovan et al, 2023 ; Krebs et al, 2023 ; Neville et al, 2023 ; Nommsen-Rivers et al, 2023 ; Smilowitz et al, 2023 ). Indeed, milk fat secretion is thought to be influenced by myriad factors within the context of the mother-milk-infant triad.…”
Introduction: Human milk delivers critical nutritional and immunological support to human infants. Milk fat globules (MFGs) and their associated membranes (MFGMs) contain the majority of milk lipids and many bioactive components that contribute to neonatal development and health, yet their compositions have not been fully defined, and the mechanisms responsible for formation of these structures remain incompletely understood.Methods: In this study, we used untargeted mass spectrometry to quantitatively profile the protein compositions of freshly obtained MFGs and their paired, physically separated MFGM fractions from 13 human milk samples. We also quantitatively profiled the MFG protein compositions of 9 pooled milk samples from 18 lactating mouse dams.Results: We identified 2,453 proteins and 2,795 proteins in the majority of human MFG and MFGM samples, respectively, and 1,577 proteins in mouse MFGs. Using paired analyses of protein abundance in MFGMs compared to MFGs (MFGM-MFG; 1% FDR), we identified 699 proteins that were more highly abundant in MFGMs (MFGM-enriched), and 201 proteins that were less abundant in MFGMs (cytoplasmic). MFGM-enriched proteins comprised membrane systems (apical plasma membrane and multiple vesicular membranes) hypothesized to be responsible for lipid and protein secretion and components of membrane transport and signaling systems. Cytoplasmic proteins included ribosomal and proteasomal systems. Comparing abundance between human and mouse MFGs, we found a positive correlation (R2 = 0.44, p < 0.0001) in the relative abundances of 1,279 proteins that were found in common across species.Discussion: Comparative pathway enrichment analyses between human and mouse samples reveal similarities in membrane trafficking and signaling pathways involved in milk fat secretion and identify potentially novel immunological components of MFGs. Our results advance knowledge of the composition and relative quantities of proteins in human and mouse MFGs in greater detail, provide a quantitative profile of specifically enriched human MFGM proteins, and identify core cellular systems involved in milk lipid secretion.
“…The need for research in this area is illustrated by the finding that tetrahydrocannabinol and cannabidiol accumulate to significant concentrations in breastmilk relative to those in plasma [ 197 ]. The little that is known about their effects on lactation and the recipient infant are summarized by WG 3 [ 55 ], and research approaches are summarized by WG 5 [ 198 ]. Alcohol, particularly in disabling alcoholism, has mostly been studied for its transfer into breastmilk and its effects on the infant; this topic is well covered by WG 3 [ 55 ].…”
“…To address the need for a framework to describe the process of translating new human milk and lactation evidence to improved guidance, standards of care, and policy [ 11 ]. This framework must reflect the need for an equitable, nonlinear process that integrates the full continuum of efforts from basic, clinical, translational, and epidemiological research to implementation science; integrates those environmental factors (i.e., physical, social or behavioral, demographic, and structural) that impact message development and adaptation; and support context-specific programs, policies, and interventions.…”
Section: The Begin Projectmentioning
confidence: 99%
“…The components of the framework suggested by WG 5 are outlined in Text Box 6 [ 11 ]. Proposed framework for translational themes (T).…”
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