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Individualized Reconstitution of Human Milk Microbiota: A Feasible Approach in Real-World Settings
Published on: February 7, 2025
A Targeted Analysis of the Donor Human Milk Metabolome and Implications for Preterm Infant Nutrition
Abigail M Galyon1, Nicole T Cacho2, Xuan He3
1Department of Nutrition, University of California, Davis, CA, United States.
Background:
Donor human milk (DHM) is widely used for preterm infants when mother's own milk (MOM) is unavailable, yet its metabolome is poorly described.
Objectives:
This study aimed to profile the metabolome of pooled, pasteurized DHM obtained from a single milk bank over a 1-y period and compare it with human milk (HM) from reference cohorts.
Methods:
Pooled DHM (n = 47) was collected weekly from the Mother's Milk Bank of Florida over 47 consecutive weeks from July 2022 to June 2023. Using 1H nuclear magnetic resonance spectroscopy, we quantified 59 polar metabolites in DHM and compared the metabolomic profile with previously published data on HM from mothers of preterm (n = 29) and term (n = 97) infants collected across the first 3 mo postpartum and analyzed using identical methods. Variability and group differences were assessed with regression, linear mixed-effects models, principal component analysis (PCA), and permutational multivariate analysis of variance (PERMANOVA); P values were false discovery rate (FDR)-adjusted.
Results:
DHM showed limited variability, as the coefficients of variation for nearly half of the metabolites were between 20% and 30%. Compared with both preterm and term colostrum and transitional milk, DHM had lower acetylcarnitine, myo-Inositol, 3'-sialyllactose, and 6'-sialyllactose (FDR-adjusted P value < 0.1). PCA separated HM by lactation stage and delivery type, with DHM clustering closest to term HM at 3 mo postpartum and farthest from preterm colostrum. PERMANOVA and dispersion testing indicated that DHM differed significantly from all HM groups (FDR-adjusted P value < 0.1), reflecting compositional differences related to lactation stage and reduced heterogeneity from pooling.
Conclusions:
Although DHM is the preferred alternative to MOM for preterm infants, it contains lower concentrations of several potentially important metabolites than preterm HM, which may be further diluted by fortification. Future studies should evaluate how these differences and fortification may affect infant growth, development, and long-term outcomes.

