MILK-Omics: Systems Biology of Human Milk and Its Links to Maternal and Infant Health

The primary objective of the project is to generate a systems-level view of human milk in the context of healthy mothers and their term infants. The study uses biospecimens and clinical data from the Mothers and Infants LinKed for Healthy Growth Study (MILk Study), a prospective observational cohort of approximately 500 exclusively breastfeeding women and their infants who are followed to 6 months of age. The project focuses on mature milk samples collected at 1 month postpartum and infant gut microbiome samples collected at 1 and 6 months of age. Specific Aim 1 is to identify maternal genetic and clinical factors that shape human milk gene expression. Using bulk and single-cell RNA sequencing of the milk cell pellet and genotypes from maternal DNA, we will identify novel genetic determinants of the milk transcriptome and assess potential modification of these genetic associations by gestational weight gain, diet, and other clinical factors. Specific Aim 2 is to describe key features of the normative human milk biosystem and their interactions with one another. Specifically, machine learning techniques will be used to characterize interaction networks and correlational structures among the following features of human milk: transcriptomics, microbiomes, oligosaccharides, metabolomics, lipidomics, and milk macronutrient composition. Specific Aim 3 is to establish how the milk biosystem is related to variation in infant gut microbiomes and health. dbGaP will house the maternal genotype and milk transcriptomics data.

The infant microbiome sequence data are associated with BioProject PRJNA1019702.

• Study Weblinks:
  • MILk Study
• Study Design:
  • Prospective Longitudinal Cohort
• Study Type:
  • Cohort
  • Dyads
  • eQTL
  • Genotype
  • Genotype/Expression
  • Individual-Level Genomic Data
  • Longitudinal Cohort
  • Mother-Child Pairs
  • Prospective
  • RNA Sequencing
• dbGaP estimated ancestry using GRAF-pop
• Total number of consented subjects: 346
• Subject Sample Telemetry Report (SSTR)

• Sequence Read Archive
• BioSample

Inclusion Criteria:

• BMI 18.5-45 kg/m² at first prenatal visit
• Pregnant women in their second or third trimester
• Maternal age 21-45 years at time of delivery
• Report during enrollment procedures of social support for and intention to exclusively breastfeed for at least 1 month
• Singleton pregnancy

Exclusion Criteria:

• Alcohol consumption >1 drink per week during pregnancy/lactation
• Tobacco consumption during pregnancy/lactation
• Inability to speak/understand English
• Known congenital metabolic, endocrine disease (other than GDM), or congenital illness affecting infant feeding
• History of type I or Type II Diabetes
• Preterm or post-term birth (gestational age <37 or >42 weeks)
• Small for gestational age birth weight (SGA, defined as <10th on CDC birth weight for gestational age charts)
• Congenital or other defect or medical condition that would affect the mother's ability to produce milk, or the infant's growth or ability to breastfeed
• Introduction of more than 8 ounces of formula, water or any other liquid other than breast milk in the first two weeks, and any liquid other than breast milk in the two weeks prior to the study visit

• Primary Phenotype: Human Milk

• Principal Investigators
  • Ellen Demerath. University of Minnesota, Minneapolis, MN USA.
  • Ran Blekhman. University of Chicago, Chicago, IL, USA.
  • Cheryl Gale. University of Minnesota, Minneapolis, MN USA.
• Co-Investigators
  • Frank Albert. University of Minnesota, Minneapolis, MN USA.
  • Eric Lock. University of Minnesota, Minneapolis, MN USA.
  • Lars Bode. University of California-San Diego, San Diego, CA USA.
  • Elvira Isganaitis. Joslin Diabetes Center, Boston, MA USA.