Genetic and genomic influences on human milk composition and impacts on infant health

Human milk is recommended as the exclusive mode of feeding for infants, but the factors influencing the hundreds of nutritive and bioactive factors in milk and their functions in the infant remain mostly unexplored. A genomics approach enables investigation of human milk as a biological system and can identify the most important factors connecting human milk composition with infant health. One such approach is milk metabolomics, which reflects the biology of the lactating mammary gland and the bioactive and nutritive components of milk that shape its function in the infant. This proposal leverages metabolomics and other cutting edge technologies to comprehensively profile the composition of human milk and its impacts on infant development. The results will provide foundational data for advancing milk research and help advance our knowledge of human nutrition during the critical first 1000 days of life. Aim 1 will identify genetic variants influencing specific milk metabolites and the genes underlying these associations, and investigate connections between the milk metabolome and infant gut microbiome. In Aim 2, the effect of human cytomegalovirus (HCMV) reactivation in the mammary gland on the milk metabolome will be assessed. HCMV is a highly prevalent virus, and postnatal exposure to HCMV via breast milk often has serious clinical consequences for preterm infants. This aim will also test for impacts of mammary HCMV reactivation and the milk metabolome on infant serum markers of inflammation. The first two aims will occur primarily during the K99 period, and will be accompanied by training in virology, immunology, and computational methods for integration of multimodal datasets. Aim 3, during the R00 phase, will investigate the impacts of human milk composition on the systems-level development of the preterm infant immune system and gut microbiome, utilizing a new cohort of preterm infants. Longitudinal sample collection will enable disentangling of the connections across these dynamic biological systems. Training in the K99 period will take place at the University of Minnesota – Twin Cities, a major research institution, with state-of-the-art core facilities for genomics and clinical/translational research. The PI will receive training from an interdisciplinary team of mentors in the departments of Pediatrics, Epidemiology & Community Health, and Genetics, Cell Biology and Development. This training plan will result in the trainee acquiring the skills and a scientific foundation to launch an independent academic career.