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Human Milk Oligosaccharides: the unique Components of Human Milk

Breast milk is nature’s most perfect source of nutrition, due to its unique composition.(1) Aside from nutrients for babies’ healthy growth and development, it offers various health benefits including protection against diarrhoea and respiratory infections.(2-5)

Human milk contains a wide range of immunologically bioactive components, such as human milk oligosaccharides (HMOs), immunoglobulins, antibodies and Living cells,which have the potential to protect against disease.(6-8)

HMOs are the third largest component of human milk, after lactose and lipids.(9-11) Their mean levels range between 10 to 15 g/L in mature human milk.(9, 11)

Naturally, human milk oligosaccharides are synthesised in the mammary gland (7, 12), and about 150 structures of HMOs have been so far clearly identified.(13) The structure of HMOs is unique to human milk and determines their biological functions.(14, 15) All HMOs contain a basic lactose (milk sugar) as the common backbone to which further specific building blocks are added in many different combinations, namely galactose, N-acetylglucosamine, fucose and sialic acid.(6, 11) As such, HMOs can be classified into fucosylated, non-fucosylated and sialylated oligosaccharides.(11, 16) 2’fucosyllactose (2’FL) and lacto-N-neotetraose (LNnT) are two among the known, most abundant human milk oligosaccharides.(9, 10, 17)

These unique complex oligosaccharides in human milk are either absent or in very low amounts in cow’s milk or any other farmed animal milk, and their variety is much lower.(18) The difference in oligosaccharide content and variety in human milk and cow milk, and thus, cow milk-based infant formulae, is likely to explain, at least in part, the differences in health outcomes between formula-fed and breastfed infants.(19)

 Professor Clemens Kunz, University Giessen, Germany

 In the last decade, remarkable and exciting research on HMOs has led to many new functions proposed for HMOs, but most of them still await to be proven in humans. These HMOs are unique to human milk.   Common prebiotics such as galacto-oligosaccharides (GOS) and fructo-oligosaccharides (FOS) are often claimed to be similar or even identical with HMOs, even though there is no structural similarity. Future   clinical studies comparing GOS/FOS and HMOs would help identify the clinical implications of such structural dissimilarities.



References

1. Agostoni C, Braegger C, Decsi T, Kolacek S, Koletzko B, Michaelsen KF, et al. Breast-feeding: a commentary by the ESPGHAN Committee on Nutrition. J Pediatr Gastroenterol Nutr. 2009;49(1):112-25.
2. Horta BL, Victora CG. Short-term effects of breastfeeding: a systematic review on the benefits of breastfeeding on diarrhoea and pneumonia mortality. World Health Organisation; 2013.
3. Bachrach VR, Schwarz E, Bachrach LR. Breastfeeding and the risk of hospitalization for respiratory disease in infancy: a meta-analysis. Arch Pediatr Adolesc Med. 2003;157(3):237-43.
4. Kramer MS, Kakuma R. Optimal duration of exclusive breastfeeding. Cochrane Database Syst Rev. 2012(8):CD003517.
5. Duijts L, Jaddoe VW, Hofman A, Moll HA. Prolonged and exclusive breastfeeding reduces the risk of infectious diseases in infancy. Pediatrics. 2010;126(1):e18-25.
6. Kunz C, Rudloff S, Baier W, Klein N, Strobel S. Oligosaccharides in human milk: structural, functional, and metabolic aspects. Annu Rev Nutr. 2000;20:699-722.
7. Rudloff S, Kunz C. Milk oligosaccharides and metabolism in infants. Adv Nutr. 2012;3(3):398S-405S.
8. Ballard O, Morrow AL. Human milk composition: nutrients and bioactive factors. Pediatr Clin North Am. 2013;60(1):49-74.
9. Zivkovic AM, German JB, Lebrilla CB, Mills DA. Human milk glycobiome and its impact on the infant gastrointestinal microbiota. Proc Natl Acad Sci U S A. 2011;108 (Suppl 1):4653-8.
10.Austin S, De Castro CA, Benet T, Hou Y, Sun H, Thakkar SK, et al. Temporal change of the content of 10 oligosaccharides in the milk of Chinese urban mothers. Nutrients. 2016;8(6).
11.Bode L. Human milk oligosaccharides: every baby needs a sugar mama. Glycobiology. 2012;22(9):1147-62.
12.Bode L. Human milk oligosaccharides: prebiotics and beyond. Nutr Rev. 2009;67 (Suppl 2):S183-91.
13.Urashima T, Hirabayashi J, Sato S, Kobata A. Human milk oligosaccharides as essential tools for basic and application studies on galectins. Trends Glycosci Glycotechnol. 2018;30(172):SJ11-SJ24.
14.Sela DA, Mills DA. Nursing our microbiota: molecular linkages between bifidobacteria and milk oligosaccharides. Trends Microbiol. 2010;18(7):298-307.
15.Bode L, Jantscher-Krenn E. Structure-function relationships of human milk oligosaccharides. Adv Nutr. 2012;3(3):383S-91S.
16.Smilowitz JT, Lebrilla CB, Mills DA, German JB, Freeman SL. Breast milk oligosaccharides: structure-function relationships in the neonate. Annu Rev Nutr. 2014;34:143-69.
17.Kunz C, Meyer C, Collado MC, Geiger L, Garcia-Mantrana I, Bertua-Rios B, et al. Influence of gestational age, secretor, and Lewis blood group status on the oligosaccharide content of human milk. J Pediatr Gastroenterol Nutr. 2017;64(5):789-98.
18.Urashima T, Taufik E, Fukuda K, Asakuma S. Recent advances in studies on milk oligosaccharides of cows and other domestic farm animals. Biosci Biotechnol Biochem. 2013;77(3):455-66.
19.Vandenplas Y, Berger B, Carnielli VP, Ksiazyk J, Lagstrom H, Sanchez Luna M, et al. Human milk oligosaccharides: 2'-fucosyllactose (2'-FL) and lacto-N-neotetraose (LNnT) in infant formula. Nutrients. 2018;10(9).

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