Background/Objectives: This study systematically analyzed the concentration dynamics of human milk oligosaccharides (HMOs) and the distribution characteristics of secretory (Se) and Lewis (Le) phenotypes in China. Methods: A total of 1462 breast milk samples were collected from lactating mothers in six major regions of China, including Changchun, Lanzhou, Chengdu, Tianjin, Guangzhou, and Shanghai. We quantified 17 major HMOs by high-performance anion exchange chromatography-pulsed amperometric detection (HPAEC-PAD), and Se/Le phenotypes were determined to evaluate regional differences and distribution patterns. Results: Total HMO concentration in breast milk showed a significant downward trend within 200 days postpartum and stabilized after 200 to 400 days. Fucosylated HMOs accounted for the highest proportion $60.0–83.0\%$, among which 2′-FL had the largest concentration $903.4–2832.7 \mathrm{m}\mathrm{g}/\mathrm{L}$; acetylated HMOs $8.4–17.6\%$ and sialylated HMOs $8.2–25.3\%$ accounted for relatively lower proportions. This study further divided breast milk into four phenotypes based on HMO characteristics: 72.49% of the samples were Se+/Le+, 6.145% were Se+/Le−, 20.12% were Se−/Le+, and 1.24% were double negative (Se−/Le−). Se+ and Le+ phenotypes accounted for 78.7% and 92.6% of the total population, respectively. The total concentration of HMOs in breast milk of different phenotypes was significantly different, with the average total HMO concentration of Se+/Le+ breast milk being the highest (8342 mg/L), while that of Se−/Le− breast milk being the lowest (4532 mg/L). Se+ phenotype was associated with higher levels of fucosylated HMOs, including 2′-fucosyllactose (2′-FL) and lacto-N-fucopentaose I (LNFP I), and lower levels of lacto-N-tetraose (LNT) and sialyl-lacto-N-tetraose b (LST b) compared to other phenotypes. Most HMOs reached their highest concentrations during the colostrum (CM) and transitional milk (TM) stages, followed by a progressive decline with lactation, with phenotype-specific variations evident across all HMOs. Notably, certain HMOs, such as 3-FL, 3′-SL, DFL, and LNDFH II, exhibited distinct temporal patterns. Conclusions: This study revealed the Se/Le phenotype distribution and dynamic characteristics of HMOs in the Chinese mother-infant population, offering a valuable reference for global breast milk composition databases and infant nutrition research.

Background: Based on our extensive cohort study, the Maternal Nutrition and Infant Investigation (MUAI), this research investigated the associations between human milk oligosaccharide (HMO) intake during the postnatal period and allergic disease development and gut microbiome composition in early childhood through long-term follow-up. Methods: Human breast milk (HBM) samples at five lactation stages and fecal samples of infants and young children were collected. Children aged 5 years included in this study were categorized into allergic and non-allergic groups via standardized allergen testing. Results: The findings indicated that higher HMO intake levels across five distinct lactation periods may be linked to a reduced incidence of allergies in children. The consumption of six major structurally representative HMOs was significantly associated with alterations in the gut microbiota profiles of young children. Moreover, there were notable differences in gut microbiota composition between allergic and non-allergic children. Specifically, beneficial bacteria such as Bifidobacterium, Akkermansia, and Ruminococcus were significantly enriched, in addition to the levels of metabolite propionic acid, a beneficial short-chain fatty acid, which were notably higher in the non-allergic group. To further validate the relationship between Bifidobacterium abundance and early HMO intake, the analysis revealed that a differential strain biomarker, Bifidobacterium adolescentis (B. adolescentis), exhibited significant correlations with specific HMOs at different lactation stages, particularly showing a strong positive correlation with 2′-fucosyllactose (2′-FL) content. Conclusions: These findings suggest that early-life HMO intake is associated with long-term differences in allergic outcomes, potentially through modulation of gut microbiota composition, particularly the enrichment of B. adolescentis.