Matching Donor Human Milk On Maternal Secretor Status (MMOMSS) Study

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Background: The gut microbiome is established early in life and plays an important role in developing the immune system and metabolism. Infants born prematurely (before 37-weeks gestation) account for 1 in 10 births worldwide and are especially vulnerable to serious microbiome-mediated illnesses suc...

Background: The gut microbiome is established early in life and plays an important role in developing the immune system and metabolism. Infants born prematurely (before 37-weeks gestation) account for 1 in 10 births worldwide and are especially vulnerable to serious microbiome-mediated illnesses such as necrotizing enterocolitis and metabolic diseases. Breastfeeding is the most important factor shaping the infant gut microbiome, providing human milk oligosaccharides (HMOs) that serve as prebiotics for beneficial gut bacteria. Donor human milk (DHM) is considered the best alternative when mothers own milk (MOM) is not available. HMO profiles are highly variable between mothers and there is currently no "matching" process to optimize pairing of DHM and recipient infants. The strongest factor influencing HMO composition is maternal secretor status, determined by the expression of a specific gene (?-1, 2-fucosyltransferase-2). About 20% of Caucasians are non-secretors and the impact of feeding DHM from secretor donors to infants of non-secretor mothers is unknown. The investigators aim to explore if matching DHM based on maternal secretor status impacts the development of the gut microbiome in preterm infants. Method: The investigators will use a pilot, randomized, controlled trial to compare two groups of very preterm infants (<32 weeks gestation): 1) infants receiving DHM matched to their mother's secretor status and 2) infants receiving standard issue (i.e. unmatched) DHM. Mothers <32 weeks gestation admitted to the antenatal unit at FMC or the antenatal community care program will be screened for eligibility. Enrolled mothers will be randomized to either the intervention (n=30; matched DHM) or control group (n=30; standard unmatched DHM). Infants of mothers assigned to the intervention group will receive "matched" DHM based on maternal secretor status, determined after randomization. Infant fecal samples will be collected weekly from soiled diapers until infants are transferred to a level II NICU or are no longer receiving donor milk. Samples of MOM and DHM will also be collected to analyse milk for HMO and nutrient content. Microbial DNA will be analyzed using 16S sequencing. Additionally, for a subset of samples selected based on 16S results, researchers will perform shotgun metagenomics to identify microbial population structures and functional capacity. Microbial composition from intervention (matched DHM), control (unmatched DHM) and reference (exclusive MOM) groups will be compared to determine differences in microbial diversity and taxonomy. Impact on healthcare: If promising, this intervention will be tested in a much larger cohort of preterm infants from NICUs across Canada. Our research could revolutionize how milk banks and neonatal intensive care units provide DHM to preterm infants. Finally, this research will expand on our understanding of the prebiotic effects of HMOs on infant microbiome and may inform future prebiotic/probiotic supplementation regimens.

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