Human breast milk (HBM) is recognized by the World Health Organization as a gold standard and ideal source of nutrition for an infant’s first 6 months of life. The nutrients in HBM can be categorized into three major components: fats, proteins and carbohydrates. A unique subset of carbohydrates found in the HBM are called Human milk Oligosaccharides (HMOs). HMOs are the third most abundant solid component in human breast milk, consisting of hundreds of unique structures. HMOs are indigestible by the infant but have shown to be very beneficial to the infant’s development, making them an intriguing constituent. However, due to the lack of standards, reliable methods for quantitation, and complexity of performing large scale analysis, there are limits to our general knowledge of their abundances and functions. We developed a comprehensive library and a high-throughput method that allows for accurate quantitation of HMOs using high resolution mass spectrometry. This method was applied to over 3000 mothers from 19 geographically diverse sites, where phenotypic variations in the mother’s milk and secretor status were observed globally.<br/><br/>The results reveal geographic variations in the milk type (as judged by representation of a(1,2)-fucosylated carbohydrate structures) as well as accompanying differences in the representation of other fucosylated and sialylated structures. Furthermore, influences based on lactation month, infant gender, and mother’s age were also investigated. Our results highlight the need for studies in mother-infant dyads to further explore the relationships between maternal health status, breastmilk HMO composition, early gut community development, the products of microbial metabolism of these HMOs, and features of infant health status.

Global variations of human milk oligosaccharides: A high-throughput LC-MS based method

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ACS Fall 2022

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