Optimizing the prebiotic profile of donor human milk for preterm infants: a protocol for the Matching Donor Human Milk On Maternal Secretor Status (MMOMSS) pilot randomized controlled trial

Abstract

Background: Breastfeeding is the most important factor shaping the infant gut microbiome, providing human milk oligosaccharides (HMOs) that serve as prebiotics for commensal gut bacteria. Donor human milk (DHM) is considered the best alternative when mothers own milk is not available. HMO profiles are highly variable among mothers and there is currently no "matching" process to optimize provision of DHM to recipient infants. The strongest factor influencing HMO composition is maternal secretor status, determined by the expression of a specific gene (α-1, 2-fucosyltransferase-2, FUT2). About 20% of the population are non-secretors and the impact of feeding DHM from secretor donors to infants of non-secretor mothers is not well understood. We aim to explore if matching DHM based on maternal secretor status impacts the development of the gut microbiome in preterm infants. Methods: This is a pilot, randomized, controlled trial of 60 mother-infant dyads, comparing microbial composition of preterm infants (<34 weeks gestation) who receive DHM matched to their mother’s secretor status to infants who receive standard issue (non-matched) DHM. Enrolled mothers will be randomized to either the intervention (n=30) or control group (n=30). Infants of mothers assigned to the intervention group will receive "matched" DHM based on maternal secretor status. Infant fecal samples will be collected weekly until discontinuation of DHM or discharge/transfer from the unit. Samples of mother’s own milk and DHM will also be collected to analyze HMO and nutrient content. Microbial DNA will be analyzed using shallow shotgun sequencing to identify microbial population structures and functional capacity. Microbial composition from intervention and control groups will be compared to determine differences in diversity and taxonomy. The Consolidated Framework for Implementation Research will be used to assess clinical feasibility of the trial in the NICU environment. Discussion: This research could better inform how milk banks and neonatal intensive care units provide DHM to preterm infants. Additionally, it will expand our understanding of the prebiotic effects of HMOs on the infant microbiome and may inform future prebiotic/probiotic supplementation regimens. Trial Registration: Registration on ClinicalTrials.gov was completed on October 17, 2019, and updated on February 11, 2022, with the Identifier: NCT04130165