Shared patterns of human milk composition link mammary gland function to infant growth
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.
Authors
- Donna Tracy Geddes (ORCID: https://orcid.org/0000-0002-0431-7078)
- Jennifer E. Van Eyk (ORCID: https://orcid.org/0000-0001-9050-148X)
- Melissa B. Manus (ORCID: https://orcid.org/0000-0003-3640-1781)
- Joann M. McDermid (ORCID: https://orcid.org/0000-0002-5829-1897)
- Andrew N. Mertens (ORCID: https://orcid.org/0000-0002-1050-6721)
- Alan Hubbard (ORCID: https://orcid.org/0000-0002-3769-0127)
- Lindsay Helen Allen (ORCID: https://orcid.org/0000-0002-8729-5213)
- Meghan B. Azad (ORCID: https://orcid.org/0000-0002-5942-4444)
- Yasir Shafiq (ORCID: https://orcid.org/0000-0003-1576-724X)
- Kim A. Lagerborg (ORCID: https://orcid.org/0000-0003-2490-2191)
- Theo J. Moraes (ORCID: https://orcid.org/0000-0001-9968-6601)
- Nima Aghaeepour (ORCID: https://orcid.org/0000-0002-6117-8764)
- Waqasuddin Khan (ORCID: https://orcid.org/0000-0001-7995-8163)
- Carl K. Lachat (ORCID: https://orcid.org/0000-0002-1389-8855)
- Setareh Shahab‐Ferdows (ORCID: https://orcid.org/0000-0002-5058-4935)
- April A. Jauhal (ORCID: https://orcid.org/0000-0003-3636-4765)
- Daniela Hampel (ORCID: https://orcid.org/0000-0003-0288-7680)
- Shelley McGuire (ORCID: https://orcid.org/0000-0001-8214-2229)
- Liat Shenhav (ORCID: https://orcid.org/0000-0003-1708-6050)
- Fyezah Jehan (ORCID: https://orcid.org/0000-0002-5874-4358)
- Trenton Dailey-Chwalibóg (ORCID: https://orcid.org/0000-0002-8204-4925)
- Padmaja Subbarao (ORCID: https://orcid.org/0000-0003-0394-1933)
- Aneela Pasha (ORCID: https://orcid.org/0000-0001-5866-8239)
- Natalie Rodriguez (ORCID: https://orcid.org/0000-0001-6669-8737)
- Laéticia Céline Toe (ORCID: https://orcid.org/0000-0002-4615-5388)
- Megan R. Beggs (ORCID: https://orcid.org/0000-0002-2690-1785)
- Lars Bode (ORCID: https://orcid.org/0000-0002-9914-9571)
- Ameer Muhammad (ORCID: https://orcid.org/0000-0001-8485-641X)
- Muhammad Imran Nisar (ORCID: https://orcid.org/0000-0002-2378-4720)
- Lishi Deng (ORCID: https://orcid.org/0000-0001-9802-5078)
- Mohit M. Jain
- Mark Daniel DeBoer (ORCID: https://orcid.org/0000-0003-1462-591X)
- Chi-Hung Shu (ORCID: https://orcid.org/0009-0009-3486-8856)
- Kelsey B. Fehr (ORCID: https://orcid.org/0000-0003-3551-8144)
- Daniel Sunko
- Pratima Niroula
- Naveed Iqbal (ORCID: https://orcid.org/0000-0001-8631-9191)
- Bianca Cordazzo Vargas (ORCID: https://orcid.org/0009-0001-9562-593X)
Institutions
- Aga Khan University (PK)
- University of British Columbia (CA)
- Balochistan University of Information Technology, Engineering and Management Sciences (PK)
- University of Antwerp (BE)
- University of Idaho (US)
- The University of Western Australia (AU)
- Hospital for Sick Children (CA)
- Aga Khan University Hospital (PK)
- Ghent University (BE)
- University of Saskatchewan (CA)
- Children's Hospital Research Institute of Manitoba (CA)
- Vital Pakistan Trust (PK)
- Stanford Medicine (US)
- Centre for Global Health Research (CA)
- Cedars-Sinai Smidt Heart Institute (US)
- AFRICSanté (BF)
- Mothers’ Milk Bank (US)
- Institut de Recherche en Sciences de la Santé (BF)
- The University of Texas at San Antonio (US)
- University of Manitoba (CA)
- University of Virginia (US)
- New York University (US)
- University of California, Davis (US)
- University of California, Berkeley (US)
- Stanford University (US)
Publication Details
- Journal
- Science
- Published
- 2026-10-08
- DOI
- https://doi.org/10.1126/science.aee7240
- Primary Topic
- Infant Nutrition and Health
- Type
- article
- Field-Weighted Citation Impact
- 0.00