Human milk variation is shaped by maternal genetics and impacts the infant gut microbiome

Kelsey E Johnson; Timothy Heisel; Mattea Allert; Annalee Fürst; Nikhila Yerabandi; Dan Knights; Katherine M Jacobs; Eric F Lock; Lars Bode; David A Fields; Michael C Rudolph; Cheryl A Gale; Frank W Albert; Ellen W Demerath; Ran Blekhman

doi:10.1101/2023.01.24.525211

Human milk variation is shaped by maternal genetics and impacts the infant gut microbiome

bioRxiv [Preprint]. 2023 Jan 25:2023.01.24.525211. doi: 10.1101/2023.01.24.525211.

Authors

Kelsey E Johnson¹, Timothy Heisel², Mattea Allert¹, Annalee Fürst³, Nikhila Yerabandi³, Dan Knights^{4

5}, Katherine M Jacobs⁶, Eric F Lock⁷, Lars Bode^{3

8}, David A Fields⁹, Michael C Rudolph¹⁰, Cheryl A Gale², Frank W Albert¹, Ellen W Demerath¹¹, Ran Blekhman¹²

Affiliations

¹ Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, USA.
² Division of Neonatology, Department of Pediatrics, University of Minnesota Medical School, Minneapolis, MN, USA.
³ Department of Pediatrics, University of California, San Diego, La Jolla, CA, USA.
⁴ BioTechnology Institute, College of Biological Sciences, University of Minnesota, Minneapolis, MN, USA.
⁵ Department of Computer Science and Engineering, University of Minnesota, Minneapolis, MN, USA.
⁶ Department of Obstetrics, Gynecology and Women's Health, Division of Maternal-Fetal Medicine, University of Minnesota Medical School, Minneapolis, MN, USA.
⁷ Division of Biostatistics, University of Minnesota School of Public Health, Minneapolis, MN, USA.
⁸ Human Milk Institute (HMI) and Mother-Milk-Infant Center of Research Excellence (MOMI CORE), University of California, San Diego, La Jolla, CA, USA.
⁹ Department of Pediatrics, the University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
¹⁰ Harold Hamm Diabetes Center, Department of Physiology, the University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
¹¹ Division of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis, MN, USA.
¹² Section of Genetic Medicine, Division of Biological Sciences, University of Chicago, Chicago, IL, USA.

Abstract

Human milk is a complex mix of nutritional and bioactive components that provide complete nutrition for the infant. However, we lack a systematic knowledge of the factors shaping milk composition and how milk variation influences infant health. Here, we used multi-omic profiling to characterize interactions between maternal genetics, milk gene expression, milk composition, and the infant fecal microbiome in 242 exclusively breastfeeding mother-infant pairs. We identified 487 genetic loci associated with milk gene expression unique to the lactating mammary gland, including loci that impacted breast cancer risk and human milk oligosaccharide concentration. Integrative analyses uncovered connections between milk gene expression and infant gut microbiome, including an association between the expression of inflammation-related genes with IL-6 concentration in milk and the abundance of Bifidobacteria in the infant gut. Our results show how an improved understanding of the genetics and genomics of human milk connects lactation biology with maternal and infant health.

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Abstract

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