Human Milk Oligosaccharide Compositions Illustrate Global Variations in Early Nutrition

Background Human milk oligosaccharides (HMOs) are an abundant class of compounds found in human milk and have been linked to the development of the infant, and specifically the brain, immune system, and gut microbiome. Objectives Advanced analytical methods were used to obtain relative quantitation of many structures in approximately 2000 samples from over 1000 mothers in urban, semirural, and rural sites across geographically diverse countries. Methods LC-MS-based analytical methods were used to profile the compounds with broad structural coverage and quantitative information. The profiles revealed their structural heterogeneity and their potential biological roles. Comparisons of HMO compositions were made between mothers of different age groups, lactation periods, infant sexes, and residing geographical locations. Results A common behavior found among all sites was a decrease in HMO abundances during lactation until approximately postnatal month 6, where they remained relatively constant. The greatest variations in structural abundances were associated with the presence of alpha(1,2)-fucosylated species. Genomic analyses of the mothers were not performed; instead, milk was phenotyped according to the abundances of alpha(1,2)-fucosylated structures. Mothers from the South American sites tended to have higher proportions of phenotypic secretors [mothers with relatively high concentrations of alpha(1,2)-fucosylated structures] in their populations compared to the rest of the globe, with Bolivia at similar to 100% secretors, Peru at similar to 97%, Brazil at similar to 90%, and Argentina at similar to 85%. Conversely, the cohort sampled in Africa manifested the lowest proportion of secretors (South Africa similar to 63%, the Gambia similar to 64%, and Malawi similar to 75%). Furthermore, we compared total abundances of HMOs in secretors compared with nonsecretors and found that nonsecretors have lower abundances of HMOs compared to secretors, regardless of geographical location. We also observed compositional differences of the 50+ most abundant HMOs between milk types and geographical locations. Conclusions This study represents the largest structural HMO study to date and reveals the general behavior of HMOs during lactation among different populations.