Maternal diet and genetics shape the human milk metabolome
- 11. Center for Genetic Epidemiology, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles
Abstract
Human milk contains a diverse array of metabolites that contribute to infant nutrition, immune development, and microbial colonization. The maternal factors shaping the milk metabolome, and the relative contribution of genetics or diet vs. other factors, remain poorly understood. Here, we profiled 458 milk metabolites in 349 one-month postpartum human milk samples and integrated metabolomic data with maternal diet, clinical, transcriptomic, and genomic measurements. Maternal diet was broadly associated with milk metabolite composition, with significant correlations identified between dietary features and 323 metabolites. Coffee consumption strongly predicted milk quinic acid and 1,3-dimethyluric acid abundance, while high-fiber dietary patterns were associated with metabolites including proline-betaine and N-acetylornithine. Integration of milk transcriptomic and metabolomic data via machine learning identified biologically plausible gene-metabolite pairs, including associations between QPRT expression and quinolinic acid, and DPEP1 and cysteine-glycine dipeptide. Genome-wide association analyses identified nine study-wide significant metabolite quantitative trait loci, including novel milk-specific associations near PDE6A affecting purine metabolites and near GNE affecting free sialic acid. Comparison with plasma metabolite studies demonstrated both shared and milk-specific genetic regulation of metabolites. Finally, we found that of all tested maternal features, diet explained the largest proportion of variation in the milk metabolome. Together, these findings demonstrate that the human milk metabolome reflects both maternal exposures and mammary gland-specific biology. This work establishes a framework for understanding how genetic and environmental factors shape milk composition.
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BibTeX
@misc{johnson2026maternal,
title = {{Maternal diet and genetics shape the human milk metabolome}},
author = {K. E. Johnson and Y. Duan and A. Youssef and J. J. Aristizabal-Henao and A. Johnson and M. A. Kiebish and E. M. Nagel and K. Palmsten and S. Pierce and S. Wernimont and L. Bode and E. F. Lock and E. M. Isganaitis and D. A. Fields and F. W. Albert and R. Blekhman and E. W. Demerath},
howpublished = {bioRxiv},
year = {2026},
month = aug,
doi = {10.64898/2026.08.11.744248},
url = {https://www.biorxiv.org/content/10.64898/2026.08.11.744248v2},
note = {CC BY},
}
RIS
TY - UNPB
TI - Maternal diet and genetics shape the human milk metabolome
AU - K. E. Johnson
AU - Y. Duan
AU - A. Youssef
AU - J. J. Aristizabal-Henao
AU - A. Johnson
AU - M. A. Kiebish
AU - E. M. Nagel
AU - K. Palmsten
AU - S. Pierce
AU - S. Wernimont
AU - L. Bode
AU - E. F. Lock
AU - E. M. Isganaitis
AU - D. A. Fields
AU - F. W. Albert
AU - R. Blekhman
AU - E. W. Demerath
PY - 2026
DA - 2026/08/11
PB - bioRxiv
DO - 10.64898/2026.08.11.744248
UR - https://www.biorxiv.org/content/10.64898/2026.08.11.744248v2
AB - Human milk contains a diverse array of metabolites that contribute to infant nutrition, immune development, and microbial colonization. The maternal factors shaping the milk metabolome, and the relative contribution of genetics or diet vs. other factors, remain poorly understood. Here, we profiled 458 milk metabolites in 349 one-month postpartum human milk samples and integrated metabolomic data with maternal diet, clinical, transcriptomic, and genomic measurements. Maternal diet was broadly associated with milk metabolite composition, with significant correlations identified between dietary features and 323 metabolites. Coffee consumption strongly predicted milk quinic acid and 1,3-dimethyluric acid abundance, while high-fiber dietary patterns were associated with metabolites including proline-betaine and N-acetylornithine. Integration of milk transcriptomic and metabolomic data via machine learning identified biologically plausible gene-metabolite pairs, including associations between QPRT expression and quinolinic acid, and DPEP1 and cysteine-glycine dipeptide. Genome-wide association analyses identified nine study-wide significant metabolite quantitative trait loci, including novel milk-specific associations near PDE6A affecting purine metabolites and near GNE affecting free sialic acid. Comparison with plasma metabolite studies demonstrated both shared and milk-specific genetic regulation of metabolites. Finally, we found that of all tested maternal features, diet explained the largest proportion of variation in the milk metabolome. Together, these findings demonstrate that the human milk metabolome reflects both maternal exposures and mammary gland-specific biology. This work establishes a framework for understanding how genetic and environmental factors shape milk composition.
ER -