Milk oligosaccharide structure

Human milk contains a high concentration of soluble oligosaccharides, which somewhat surprisingly exceeds the protein content  (Coppa et al., 1993). The concentration of milk oligosaccharides vary by individual and declines over the course of lactation, but it is generally understood to be present at  ≥ 4 g/L in milk with higher levels observed in colostrums (Asakuma et al., 2008; Chaturvedi et al., 2001). Milk oligosaccharides incorporate D-glucose, D-galactose, N-acetylglucosamine, L-fucose and sialic acid monosaccharides assembled in various configurations. Lactose (Galß1-4Glc) is predominately found at the reducing end and is elongated from a ß1-3 linkage (an additional ß 1-6 linkage is found in some branched forms) with several repeating N-acetyllactosamine units (Galß1-3/4GlcNAc). Further complexity is provided by terminal fucosylation via α1-2/3/4 linkages and/or α2-3/6 sialylation. Almost 200 distinct molecular species have been identified in pooled breast milk samples to date (Ninonuevo et al., 2006). When considering the immense combinatorial potential for these molecules, the identification of relatively few structures suggest that their biosynthesis within the mammary epithelia has been constrained by a functional imperative.  Accordingly, HMO structures vary among maternal genotypes, with the particular complement of oligosaccharides present in mother’s milk dependant on Lewis and secretor status (Kunz et al., 2000). Further information on HMO structure and function is provided by recent reviews on the topic (Bode, 2006; German et al., 2008).

 

A cartoon depicting HMOs combinatorial potential

 

References

Asakuma, S., et al., 2008. Variation of major neutral oligosaccharides levels in human colostrum. Eur J Clin Nutr. 62, 488-94. PMID: 17375110

Bode, L., 2006. Recent advances on structure, metabolism, and function of human milk oligosaccharides. J Nutr. 136, 2127-30. PMID: 16857829

Chaturvedi, P., et al., 2001. Fucosylated human milk oligosaccharides vary between individuals and over the course of lactation. Glycobiology. 11, 365-72. PMID: 11425797

Coppa, G. V., et al., 1993. Changes in carbohydrate composition in human milk over 4 months of lactation. Pediatrics. 91, 637-41. PMID: 8441573

German, J. B., et al., 2008. Human milk oligosaccharides: evolution, structures and bioselectivity as substrates for intestinal bacteria. Nestle Nutr Workshop Ser Pediatr Program. 62, 205-18; discussion 218-22. PMID: 18626202

Kunz, C., et al., 2000. Oligosaccharides in human milk: structural, functional, and metabolic aspects. Annu Rev Nutr. 20, 699-722. PMID: 10940350

Ninonuevo, M. R., et al., 2006. A strategy for annotating the human milk glycome. J Agric Food Chem. 54, 7471-80. PMID: 17002410