An exploratory analysis of the associations of human milk oligosaccharides and N-/O-glycans with infectious and allergic outcomes in the first year of life: the Japanese Human Milk Study Cohort.

PURPOSE: This exploratory study examined the associations of human milk oligosaccharides (HMOs) and N-/O-glycans in human milk with infectious and allergic outcomes during infancy. METHODS: This prospective cohort study included 200 Japanese mother-infant dyads selected from the Japanese Human Milk Study Cohort. Human milk samples were collected at 1-2 months postpartum, and 11 HMOs and 28 N-/O-glycans were measured. HMOs were measured as absolute concentrations, whereas N-/O-glycans were expressed as relative abundances based on normalized LC-MS signal intensity. Infant histories of infections and allergies during the first year of life were assessed using self-administered questionnaires. Associations between milk glycan components and infant health outcomes were evaluated using Firth's penalized likelihood logistic regression. To aid interpretation of multiple glycan-outcome comparisons, q values were calculated within each outcome at each step of the hierarchical analysis using the Benjamini-Hochberg procedure for controlling the false discovery rate. RESULTS: In Firth logistic regression analyses, several milk glycans showed nominal associations with infectious or allergic outcomes. Total sialic acid, disialylated N-glycans (N51 and N57), and 6'-sialyllactose showed nominal associations with lower odds of bronchitis, whereas total HMO showed a nominal association with higher odds of otitis media. However, no individual HMO showed a nominal association with this outcome. For food allergy, 3-fucosyllactose, lacto-N-fucopentaose II, and fucosyl-sialyl O-glycan (O24) showed nominal associations with lower odds, whereas 2'-fucosyllactose showed a nominal association with higher odds in the overall analysis. However, all infants who developed food allergy were born to secretor mothers, and several food allergy findings were attenuated in the analysis restricted to secretor mothers. For atopic dermatitis, high-mannose-type N-glycans, particularly N12 and N33, showed nominal associations with higher odds. No glycan-outcome association had a q value below 0.05 within each outcome and step of the hierarchical analysis. CONCLUSION: Several human milk glycans showed nominal associations with infectious or allergic outcomes during infancy. However, none had a q value below 0.05 after false discovery rate correction. These findings should be interpreted as exploratory and hypothesis-generating and require validation in larger independent cohorts.