Quantitative Profiling of Human Milk Oligosaccharides Across Asian Countries Reveals Secretor-Dependent Variations and Implications for Infant Nutrition

Human milk oligosaccharides (HMOs) exhibit substantial inter-individual and secretor-dependent variation, yet comprehensive quantitative data across diverse maternal phenotypes remain limited. In this study, we analyzed 578 human milk samples from four Asian populations using a dual mass spectrometry approach, combining quadrupole time-of-flight (Q-TOF) for structural profiling and triple quadrupole (QQQ) mass spectrometry for absolute quantitation of 15 major HMOs. Samples were classified into Secretor (76.7%) and Non-Secretor (23.3%) groups based on α-1,2-fucosylated HMO profiles. Secretor milk was enriched in α-1,2-fucosylated HMOs, whereas Non-Secretor milk showed markedly reduced levels of these structures. However, Non-Secretor retained substantial total fucosylated HMOs (65-76% of Secretor levels), accompanied by increased α-1,3/4-fucosylated structures, including up to 3.2-fold higher levels of 3-fucosyllactose (3-FL). Sensitive QQQ quantitation further revealed trace levels of α-1,2-fucosylated HMOs in Non-Secretor at concentrations 10-100-fold lower than in Secretor. Correlation analysis indicated an inverse relationship between α-1,2- and α-1,3-fucosylation patterns, consistent with redistribution of fucosylation pathways. These findings suggest that the Non-Secretor phenotype represents a distinct compositional state rather than a simple loss of α-1,2-fucosylation and provide a quantitative framework for phenotype-informed nutritional strategies.