Human Milk Reveals Molecular Clues Linking Maternal Nutrition to Infant Growth

Human milk has long been celebrated as the perfect first food, but a new study suggests it is far more than a delivery system for nutrients. Research led by scientists at NYU Grossman School of Medicine, published online October 8 in the journal Science, shows that the molecular patterns circulating in milk can serve as a real-time readout of the lactating mammary gland itself, connecting maternal nutrition, gland biology, and infant growth in ways that have never been captured before. By analyzing thousands of molecular measurements from mothers in three nutritionally distinct populations, the team identified shared signatures in milk composition that track both a mother’s nutritional status and her baby’s early development.

The central insight of the work is deceptively simple: because milk is produced by the mammary gland, its composition should carry information about the functional state of the organ that makes it. To test this idea, the researchers framed mammary gland function as three interconnected biological processes. The first is milk synthesis and secretion, the cellular machinery that manufactures milk components and releases them into the ductal system. The second involves the epithelial barrier and tissue remodeling, which govern what passes between the bloodstream and the milk while continuously reshaping the milk-producing tissue. The third encompasses immune and repair activity, which protects the gland from stress and restores tissue after injury. By mapping molecular patterns in milk onto these processes, the team asked not merely what is present in milk, but what that composition reveals about the gland producing it.

“Human milk gives us a rare, non-invasive window into the biology of the lactating mammary gland,” said Liat Shenhav, PhD, senior author of the study and an assistant professor at NYU Grossman School of Medicine with appointments in the Institute for Systems Genetics, the Department of Microbiology, and the Department of Obstetrics and Gynecology. “By looking at molecular patterns across diverse populations, we can begin to identify shared features of mammary function and understand how maternal nutritional and metabolic state relates to milk composition and infant growth.”

Despite the mammary gland’s central role in early life, how its functional state shapes milk composition, and how that variation relates to infant growth, has remained poorly understood. Human milk contains thousands of nutrients, metabolites, proteins, immune factors, and other molecules, but research has often examined these components one at a time rather than as an integrated biological system. The new study took a different approach. Across 1,543 human milk samples drawn from three cohorts in Canada, Pakistan, and Burkina Faso, the researchers combined multiple molecular layers, including metabolites, proteins, micronutrients such as vitamins, macronutrients such as carbohydrates, and human milk oligosaccharides, together with infant growth data and computational approaches including machine learning, a form of artificial intelligence.

The analysis drew on two randomized nutritional trials in which maternal supplementation promoted recovery or stability among infants at higher risk for poor growth. Multi-omic analyses, which integrate information across several molecule types such as proteins and metabolites to provide a complete picture of a biological system, revealed a shared pattern of milk composition associated with both maternal supplementation and infant growth. In other words, the same molecular signatures that shifted when mothers received nutritional support also tracked how well their infants were growing, suggesting a measurable molecular bridge between what mothers consume and how their babies develop.

The researchers then examined which molecules most consistently contributed to these shared nutrition-growth patterns. Their analysis identified seven candidate biomarkers linked to maternal nutritional status, infant growth, and biological programs related to mammary gland function. Four of the markers, C2, C3, C4, and C5, were short-chain acylcarnitines, molecules that help cells process nutrients for energy. The remaining three were lysine, an amino acid; 6′-sialyllactose, a human milk oligosaccharide; and selenium, a mineral. Together, the seven biomarkers captured complementary aspects of mammary biology, including milk synthesis, tissue remodeling, and immune response activity, and extended beyond established measures of blood-milk barrier permeability.

Short-chain acylcarnitines showed the strongest links across mammary functional domains, with C5 emerging as a particularly prominent signal. Higher C5 levels were associated with reduced milk synthesis signatures and with biological patterns related to tissue remodeling and immune activity. Because C5 stood out as a central metabolic signal, the researchers investigated which nutritional factors might explain variation in acylcarnitine levels. Acylcarnitine metabolism depends on coenzyme A, or CoA, a central molecule in energy and lipid metabolism that is synthesized from pantothenic acid, better known as vitamin B5. Drawing on associations across cohorts and established metabolic biology, the researchers propose that low vitamin B5 availability may constrain CoA-dependent metabolism and contribute to altered acylcarnitine profiles, including the accumulation of C5.

“Our findings demonstrate the intimate link between maternal nutrition, metabolic health and mammary function, highlighting the importance of an integrative approach to supporting maternal and infant health,” said first author Dr. April Jauhal of the Shenhav lab at NYU Grossman School of Medicine. “One plausible route linking maternal nutrition to mammary metabolism in our data is via the pantothenic-CoA-C5 metabolic pathway, and we are currently investigating the functional role of this pathway in mammary biology and lactation.”

The framing of milk as a biological window also places lactation within a broader continuum of maternal physiology that begins during pregnancy. During gestation, the mammary gland undergoes extensive hormonal differentiation, tissue and immune remodeling, and metabolic programming, while its major functional phenotype, lactation, becomes apparent only after delivery. In this sense, the mammary gland can be viewed as a postnatal maternal-infant interface: an organ programmed during pregnancy that subsequently connects maternal biology and nutrition with the developing infant. Like the placenta during pregnancy, it sits at a critical interface between mother and child, but human milk offers something the placenta cannot, a way to study that interface repeatedly and non-invasively after birth. Because milk samples can be collected over time, researchers can track how mammary function evolves across lactation without invasive procedures.

Building on this work, the Shenhav Lab is developing an integrated computational and experimental framework to test potential nutritional bottlenecks that may constrain mammary metabolism and milk production, including the vitamin B5-coenzyme A-C5 pathway. The lab is also studying colostrum and transitional milk to understand how mammary functional states emerge during the shift from pregnancy to mature lactation, and whether early molecular changes in milk reflect the emergence of mammary metabolic, barrier, and secretory function. The study is one of two complementary papers published in Science arising from the International Milk Composition, or IMiC, Consortium, an international research effort conducted in collaboration with Meghan Azad of the University of Manitoba and funded by the Gates Foundation.

The IMiC Consortium brought together more than 1,000 mother-infant pairs and profiled more than 25,000 molecular features in human milk. While the NYU Grossman-led study asked what milk composition can reveal about mammary gland function and its relationship with infant growth, the companion study asked a complementary question: which components of human milk can be changed through maternal nutrition? That companion study found that supplementation during lactation increased several B vitamins in milk, while many other milk components remained comparatively stable. Together, the two papers aim to determine how maternal nutritional and metabolic state during pregnancy and postpartum shapes mammary function, how that state is reflected in milk, and how these processes relate to infant development.

“The studies show that human milk is neither fixed nor simply a reflection of what a mother eats,” said Dr. Shenhav. “Some components respond to maternal nutrition, while others remain stable or appear to reflect broader biological states within the mammary gland. Understanding that distinction is essential if we want to design interventions that meaningfully support maternal and infant health.” The distinction matters practically as well as scientifically: if certain milk components are responsive to diet while others are buffered by gland biology, nutritional interventions can be targeted at the molecules most likely to change, rather than applied indiscriminately.

“Ultimately, we want to understand milk in the context of the biology that produces it,” said Dr. Shenhav. “The mammary gland sits at a critical interface between maternal physiology and the developing infant. By understanding how maternal metabolism influences mammary function and milk composition, we can begin to uncover the biological pathways linking maternal nutritional status with infant growth.” The work was funded by the Gates Foundation, the National Institutes of Health, the Canadian Institutes of Health Research, and a range of additional public and private supporters. For a field that has often treated milk as a static list of ingredients, the study marks a conceptual shift toward viewing it as a dynamic, system-level readout of one of the most remarkable organs in human physiology.

Subject of Research: Molecular patterns in human milk linking maternal nutrition, mammary gland function, and infant growth

Article Title: Human milk offers a window into mammary gland function—and its links to infant growth

Article References: Human milk offers a window into mammary gland function—and its links to infant growth. (n.d.). Original publication

Image Credits: AI Generated

DOI: Not provided

Keywords: human milk, mammary gland, lactation, maternal nutrition, infant growth, acylcarnitines, vitamin B5, coenzyme A, multi-omics, human milk oligosaccharides, machine learning, biomarkers