Longitudinal changes of human milk oligosaccharides in Japan and their associations with maternal or infant characteristics.

Introduction: Human milk oligosaccharides (HMOs) are the third most abundant solid component in human milk and contribute to infant gut microbiota development, immune maturation, and neurodevelopment. Their composition varies according to genetic factors, particularly maternal Secretor and Lewis phenotypes, as well as lactation stage. However, comprehensive data on longitudinal HMO profiles and genetic phenotypes in Japanese mothers remain limited. This study aimed to characterize longitudinal HMO profiles in Japanese mothers at three lactation stages, classify samples into four Secretor/Lewis groups, and exploratorily evaluate differences associated with maternal and infant characteristics. Methods: Human milk samples and data were obtained from 270 mothers in the Chiba Study of Mother and Child Health (C-MACH). Samples were collected at colostrum, 1 month, and 4 months postpartum, resulting in 570 samples. Fifteen major HMOs were quantified, and mothers were classified into four milk groups based on Secretor (Se) and Lewis (Le) phenotypes (Se Results: The distribution of milk groups was Se Conclusions: This study provides the first comprehensive description of longitudinal HMO profiles in Japanese mothers stratified according to Secretor/Lewis groups. Distinct temporal patterns were identified across milk groups, and exploratory findings suggest potential group-specific associations between parity and certain HMOs. These results contribute to the understanding of interindividual variability in HMO synthesis and provide foundational data for future mechanistic and population-based studies.