Comparing Parent's Own Milk and Donor Milk: Differences in Viable Microbiota and Human Milk Oligosaccharide Composition and Their Influence on the Very Preterm Infant

/ABSTRACT Infants born preterm do not grow as well as their term counterparts. Poor growth during the neonatal intensive care unit admission is associated with worse neurobehavioral outcomes. Furthermore, poor infant growth and neurodevelopment have been linked with gut microbial changes. One protective driver of the infant gut microbiome is the consumption of parent’s own milk (POM). POM contains its own microbiome and human milk oligosaccharides (HMOs) unique to each parent-infant dyad. HMOs and the milk microbiome contribute to the infant gut microbiome. However, many preterm-delivering lactating parents do not have sufficient POM, requiring supplementation with donor human milk (DHM). DHM is pasteurized and pooled from multiple, mostly term donors, which likely alters HMO composition and decreases live bacteria. We hypothesize that these differences between POM and DHM likely alter the preterm infant gut microbiome and reduce the infant’s growth from birth to 36 weeks corrected gestational age. To test this hypothesis, we will leverage ongoing sampling from a funded cohort of parent-infant dyads born between 24 to 32 weeks gestation of age to examine milk microbiome (live and nonviable), HMO composition, and how these relate to infant gut microbiome and infant growth. The Specific Aims are to: 1) determine the milk microbial and HMO composition of preterm POM collected at weeks 1, 4, and 8 postpartum compared to DHM; 2) evaluate which HMO and milk microbiota (live and nonviable) are associated with infant gut microbial diversity and composition at weeks 1, 4, and 8 of age; and 3) evaluate which HMO, milk microbiota, and stool microbiota are associated with anthropometric z-score changes from birth to 36 weeks corrected gestational age. We will utilize high performance liquid chromatography for HMO analysis, metagenomic sequencing to characterize milk and stool microbiome, and propidium monoazide to distinguish live versus nonviable bacteria in milk. Growth will be measured by changes in weight, length, and head circumference z-scores from birth to 36 weeks corrected gestational age. Career Development Objectives are to 1) acquire essential knowledge in milk as a bioactive system by gaining advanced skills in systems biology and experimental design, 2) develop core competencies in multi-omic clinical- translational trial design and bioinformatic analysis, and 3) attain sophisticated skills in ethical and equitable study management, scientific writing, presentation, and grant preparation. After completion of the career development objectives and the research specific aims, the applicant will be well-positioned to obtain external funding and conduct clinical-translational studies on nutrition and growth in vulnerable parent-infant dyads. Study Impact: This study will identify critical differences between POM and DHM and their impact on the preterm infant gut microbiome and growth. The data will inform potential pre-biotic and pro-biotic supplementation for DHM in future randomized, placebo-controlled trials. Project Number: 1K23HD116933-01A1 | Fiscal Year: 2025 | NIH Institute/Center: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) | Principal Investigator: Katie Strobel | Institution: UNIVERSITY OF WASHINGTON, SEATTLE, WA | Award Amount: $161,892 | Activity Code: K23 | Study Section: Pediatrics Study Section[CHHD-A] View on NIH RePORTER: https://reporter.nih.gov/project-details/1K23HD11693301A1