Objectives: Extensive variability in human milk (HM) bioactive composition exists between women, even with similar diets, highlighting the complexity of factors modulating HM bioactive profiles. The objective of this study was to carry out a secondary analysis to explore relationships between maternal FUT2 secretor phenotype, diet and HM bioactive profiles (oligosaccharides [HMOs] and polyphenol metabolites) within the context of a Mediterranean dietary intervention. Methods: In this pilot study, 16 exclusively breastfeeding women with obesity (body mass index (BMI) ≥ 30 kg/m2) enrolled between 4 and 5 mo postpartum and were provided a 4-wk meal plan modeled on the Mediterranean diet. HM was collected for 24 hr at baseline and post-intervention. 13 mother-infant dyads completed the study. Maternal FUT2 secretor phenotype was determined by 2'-fucosyllactose concentration in HM (< 100 nmol/ml, non-secretor). Concentrations of 19 HMOs and 16 polyphenol metabolites were determined by HPLC and UPLC-MS/MS, respectively. Results: The change in human milk content of HMOs lacto-N-tetraose (LNT, p = 0.008), lacto-N-fucopentaose II (LNFP II, p = 0.05), LNFP III (p = 0.07), difucosyllacto-N-tetraose (DFLNT, p = 0.10), disialyllacto-N-tetraose (DSLNT, p = 0.01), and microbial-derived polyphenol metabolites 4-hydroxybenzoic acid (4-HBA, p = 0.10), ferulic acid (FA, p = 0.09), and hydroxyphenylpropionic acids (OH-PPAs, p = 0.04) over the intervention time frame was differentially associated with maternal secretor status. An interaction between time and maternal secretor status was observed for LNT (p = 0.01), LNFP II (p = 0.01), DSLNT (p = 0.004), and FA (p = 0.09). Increased concentrations of LNT, DSLNT, 4-HBA, and FA for secretors as well as decreased concentrations of LNT, LNFP II, LNFP III, DFLNT, and OH-PPAs for non-secretors were observed over the 4-week intervention. Conclusions: The influence of maternal diet on HM bioactive composition differs based on maternal secretor status. Consideration of non-dietary factors is needed to link maternal diet to modification of HM bioactive composition. Funding Sources: USDA ARS #6026-51000-010-05S and #6026-51000-012-06S, NIH/NIDDK R01DK107516, Arkansas Children's Research Institute/Arkansas Biosciences Institute GR037121.
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