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Seven molecules in human milk linked to infant growth and maternal nutrition
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Science

Seven molecules in human milk linked to infant growth and maternal nutrition

An international study of over 1,500 milk samples identifies biomarkers that connect maternal nutrition to a baby's development.

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Researchers have identified seven molecules in human milk that could help explain how a mother's nutritional status connects to her baby's growth.

The study, published in the journal Science, analyzed 1,543 milk samples from three geographically and nutritionally diverse cohorts in Canada, Pakistan and Burkina Faso.

"Human milk gives us a rare, non-invasive window into the biology of the lactating mammary gland," said Liat Shenhav, PhD, the study’s senior author and an assistant professor at NYU Grossman School of Medicine.

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"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."

The research is one of two complementary papers published in Science from the International Milk Composition Consortium.

Conducted in collaboration with Meghan Azad of the University of Manitoba and funded by the Gates Foundation, the international effort brought together more than 1,000 mother-infant pairs and profiled more than 25,000 molecular features in human milk.

For the NYU-led analysis, researchers integrated measurements of metabolites, proteins, micronutrients such as vitamins, macronutrients such as carbohydrates, and human milk oligosaccharides, a group of complex sugars.

This multi-omics approach examined several types of molecules together to build a fuller picture of a biological system.

The team analyzed these measurements alongside infant growth data using computational tools, including machine learning, a form of artificial intelligence.

They identified seven candidate biomarkers associated with maternal nutritional status, infant growth, and biological processes within the mammary gland.

Four were short-chain acylcarnitines, called C2, C3, C4, and C5, which help cells process nutrients for energy.

The remaining three were the amino acid lysine, the complex sugar 6′ sialyllactose, a human milk oligosaccharide, and the mineral selenium.

Together, these candidate biomarkers captured complementary aspects of mammary function, extending beyond established measures of blood-milk barrier permeability.

The acylcarnitines showed the strongest links across the gland’s different functions, particularly C5.

Higher C5 levels were associated with molecular signatures of reduced milk synthesis and with patterns related to tissue remodeling and immune activity.

Drawing on established biology, the researchers proposed that too little available vitamin B5 may restrict CoA-dependent metabolism and alter acylcarnitine profiles, potentially allowing C5 to accumulate.

"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."

In two randomized nutritional trials, maternal supplementation promoted recovery or stability in growth among infants at higher risk of poor growth.

The molecular analyses also revealed a shared pattern in milk composition associated with both supplementation and infant growth.

The companion study examined which milk components could be changed through maternal nutrition.

It found that supplementation during lactation increased several B vitamins in milk, while many other components remained comparatively stable.

"The studies show that human milk is neither fixed nor simply a reflection of what a mother eats," said 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 Shenhav Lab is developing a framework that combines computational and experimental work to test potential nutritional bottlenecks that may constrain mammary metabolism and milk production.

"Ultimately, we want to understand milk in the context of the biology that produces it," said 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."

With files from SciTechDaily