Long-Term Associations of Early-Life Human Milk Oligosaccharide Intake with Allergic Disease Development and Gut Microbiota Profiles in 5-Year-Old Children

<b>Background</b>: 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. <b>Methods</b>: 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. <b>Results</b>: 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 <i>Bifidobacterium</i>, <i>Akkermansia</i>, and <i>Ruminococcus</i> 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 <i>Bifidobacterium</i> abundance and early HMO intake, the analysis revealed that a differential strain biomarker, <i>Bifidobacterium adolescentis</i> (<i>B. adolescentis</i>), exhibited significant correlations with specific HMOs at different lactation stages, particularly showing a strong positive correlation with 2'-fucosyllactose (2'-FL) content. <b>Conclusions</b>: 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 <i>B. adolescentis</i>.