Shared patterns of human milk composition link mammary gland function to infant growth
Abstract
The mammary gland produces nutrient-rich human milk (HM), yet how mammary functional state shapes HM composition and infant outcomes remains poorly understood. We used HM multi-omics - metabolomics, proteomics, micronutrients, macronutrients, and HM oligosaccharides - across 1,543 samples from three cohorts, including two randomized trials, as a noninvasive readout of mammary functional state. Trajectory modeling and multi-omic integration showed that maternal supplementation improved recovery from early growth faltering and revealed a shared HM compositional axis linking maternal nutrition to infant growth. Machine learning, with Human Protein Atlas–informed proteomics, identified seven HM biomarkers reflecting variation across key mammary domains, indexing milk synthesis, barrier integrity, and immune/repair activity. Elevated valerylcarnitine and low pantothenic acid emerged as metabolic signals linking mammary functional state to infant growth.
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Authors: April A. Jauhal, Bianca Cordazzo Vargas, Daniel Sunko, Pratima Niroula, Lishi Deng, Laéticia Céline Toe, Ameer Muhammad, Aneela Pasha, Yasir Shafiq, Naveed Iqbal, Waqasuddin Khan, Andrew N. Mertens, Kelsey B. Fehr, Joann M. McDermid, Melissa B. Manus, Chi-Hung Shu, Daniela Hampel, Setareh Shahab‐Ferdows, Megan R. Beggs, Kim A. Lagerborg, Mohit M. Jain, Carl K. Lachat, Mark Daniel DeBoer, Jennifer E. Van Eyk, Natalie Rodriguez, Theo J. Moraes, Padmaja Subbarao, Alan Hubbard, Muhammad Imran Nisar, Lars Bode, Lindsay Helen Allen, Donna Tracy Geddes, Shelley McGuire, Nima Aghaeepour, Trenton Dailey-Chwalibóg, Fyezah Jehan, Meghan B. Azad, Liat Shenhav
Institutions: University of British Columbia, University of Virginia, University of Antwerp, Ghent University, Stanford University, New York University, The University of Texas at San Antonio, Stanford Medicine, The University of Western Australia, University of California, Berkeley, Hospital for Sick Children, University of Manitoba, University of California, Davis, University of Saskatchewan, Institut de Recherche en Sciences de la Santé, University of Idaho, Centre for Global Health Research, Children's Hospital Research Institute of Manitoba, Balochistan University of Information Technology, Engineering and Management Sciences, Aga Khan University, Mothers’ Milk Bank, Aga Khan University Hospital, Cedars-Sinai Smidt Heart Institute, Vital Pakistan Trust, AFRICSanté