What Are Human Milk Oligosaccharides?A Healthcare Professional Backgrounder

What Are Human Milk Oligosaccharides (HMO)?

Human Milk Oligosaccharides (HMOs) are the 3rd most abundant solid component in human milk.1 These unique prebiotics, that resist digestion by human intestinal enzymes,2 support the developing immune system3 and are associated with reduced risk of gastrointestinal and respiratory illness.4

HMOs and Immune Development

Aside from prebiotic effects, research has identified several potential modes of action for HMOs:

• Modulation of cytokine expression to decrease inflammation5,6,7

• Modulation of signaling pathways involved in the innate immune system5,6,8

• Modulation of gut epithelial cell differentiation and maturation9,10

70% of immune cells reside in the digestive tract, and may interact directly with HMOs consumed by infants.11 About 1% of HMOs consumed are absorbed systemically into the body,3 opening up the possibility that they could have effects beyond the gut lumen.

Human Milk Oligosaccharides – third most abundant solid component in breast milk

Infection,Inflammation

FoodAllergies

NEC,Sepsis

MicrobiotaGutHealth

EMERGING RESEARCH SHOWS MULTIPLE AREAS

MAY BE POSITIVELY IMPACTED BY HUMAN MILK

OLIGOSACCHARIDES

HMO

What is 2’-Fucosyllactose?

2’-fucosyllactose (2’-FL) is a trisaccharide consisting of glucose, galactose, and fucose. It is the most abundant HMO in a majority of mothers’ milk.12 Approximately 80% of women have the enzyme (FUT2) that enables them to make and secrete 2’-FL in their breast milk.13

Preclinical Research of 2’-FL

In addition to prebiotic effects14,15 and inhibition of pathogenic bacteria,15,16 preclinical research has shown 2’-FL beneficially impacted synaptic plasticity,17 learning and memory,17,18 and gut motility.19 2’-FL has been shown to block binding of several gut pathogens by acting as a receptor decoy14,20 and to reduce necrotizing enterocolitis.21 2’-FL has also been shown to attenuate inflammation through modulation of CD14 expression in human enterocytes.6

Clinical Research of 2’-FL

Commercially produced 2’-FL, which is structurally identical to 2’-FL in human milk,22 has now been evaluated in human clinical studies.23,24,25 Clinical studies have shown that infant formula containing 2’-FL is safe and well tolerated.23, 24 2’-FL in formula was absorbed and excreted similar to 2'-FL in human milk.23 In addition, in a clinical study,25 2'-FL HMO was shown to lower levels of multiple inflammatory cytokines to be more like levels in breastfed infants.25

2’-Fucosyllactose – a multifunctional prebiotic found in human milk

Chemical structure of 2’-fucosyllactose

24

Glucose

Galactose

Fucose

1. Chen X. Human milk oligosaccharides (HMOs): structure, function, and enzyme-catalyzed synthesis. Adv Carbohydr Chem Biochem. 2015;72:113-90.

2. Engfer MB, Stahl B, Finke B, Sawatzki G, Daniel H. Human milk oligosaccharides are resistant to enzymatic hydrolysis in the upper gastrointestinal tract. Am J Clin Nutr. 2000;71(6):1589-96.

3. Bode L. Human milk oligosaccharides: every baby needs a sugar mama. Glycobiology. 2012; 22(9):1147-62.

4. Stepans MB, Wilhelm SL, Hertzog M, Rodehorst TK, Blaney S, Clemens B, Polak JJ, Newburg DS. Early consumption of human milk oligosaccharides is inversely related to subsequent risk of respiratory and enteric disease in infants. Breastfeed Med. 2006;1:207-215.

5. He Y, Lawlor NT, Newburg DS. Human milk components modulate toll-like receptor-mediated inflammation. Adv Nutr. 2016;7:102-111.

6. He Y, Liu S, Kling DE, Leone S, Lawlor NT, Huang Y, Feinberg SB, Hill DR, Newburg DS. The human milk oligosaccharide 2'-fucosyllactose modulates CD14 expression in human enterocytes, thereby attenuating LPS-induced inflammation. Gut. 2016; 65(1):33-46.

7. Wickramasinghe S, Pacheco AR, LeMay DG, Mills DA. Bifidobacteria grown on human milk oligosaccharides downregulate the expression of inflammation-related genes in Caco-2 cells. BMC Microbiology. 2015;15:172.

8. Kulinich A, Liu L. Human milk oligosaccharides: The role in the fine-tuning of innate immune responses. Carbohydrate Research. 2016;432:62-70.

9. Holscher HD, Davis SR, Tappenden KA. Human milk oligosaccharides influence maturation of human intestinal Caco-2Bbe and HT-29 cell lines. J Nutr. 2014;144(5):586-91.

10. Kuntz S, Rudloff S, Kunz C. Oligosaccharides from human milk influence growth-related characteristics of intestinally transformed and non-transformed intestinal cells. Br J Nutr. 2008; 99:462–71.

11. Furness JB, Kunze WA, Clerc N. Nutrient tasting and signaling mechanisms in the gut II: the intestine as a sensory organ: neural, endocrine and immune responses. Am J Physiol Gastrointest Liver Physiol. 1999; 277:G922-G928.

12. Erney RM, Malone WT, Skelding MB, Marcon AA, Kleman-Leyer KM, O'Ryan ML, Ruiz-Palacios G, Hilty MD, Pickering LK, Prieto PA. Variability of human milk neutral oligosaccharides in a diverse population. J Pediatr Gastroenterol Nutr. 2000; 30(2):181-92.

13. Daniels, Geoff. Human Blood Groups, Second Edition. Malden: Blackwell Science Ltd., 2002. Print.

14. Newburg DS. Neonatal protection by an innate immune system of human milk consisting of oligosaccharides and glycans. J Anim Sci. 2009; 87 (13 Suppl):26-34.

15. Yu ZT, Chen C, Kling DE, Liu B, McCoy JM, Merighi M, Heidtman M, Newburg DS. The principal fucosylated oligosaccharides of human milk exhibit prebiotic properties on cultured infant microbiota. Glycobiology. 2013;23(2):169-77.

16. Hoeflinger JL, Davis SR, Chow J, Miller MJ. In vitro impact of human milk oligosaccharides on Enterobacteriaceae growth. J Agric Food Chem. 2015;63(12):3295-302.

17. Vázquez E, Barranco A, Ramírez M, Gruart A, Delgado-García JM, Martínez-Lara E, Blanco S, Martín MJ, Castanys E, Buck R, Prieto P, Rueda R. Effects of a human milk oligosaccharide, 2'-fucosyllactose, on hippocampal long-term potentiation and learning capabilities in rodents. J Nutr Biochem. 2015;26(5):455-65.

18. Oliveros E, Ramirez M, Vazquez E, Barranco A, Gruart A, Delgado-Garcia JM, Buck R4, Rueda R, Martin MJ. Oral supplementation of 2'-fucosyllactose during lactation improves memory and learning in rats. J Nutr Biochem. 2016; 31:20-7.

19. Bienenstock J, Buck RH, Linke H, Forsythe P, Stanisz AM, Kunze WA. Fucosylated but not sialylated milk oligosaccharides diminish colon motor contractions. PLoS One. 2013; 2;8(10):e76236.

20. Weichert S, Koromyslova A, Singh BK, Hansman S, Jennewein S, Schroten H, Hansman GS. Structural basis for norovirus inhibition by human milk oligosaccharides. J Virol. 2016;14;90(9):4843-8.

21. Autran CA, Schoterman MH, Jantscher-Krenn E, Kamerling JP, Bode L. Sialylated galacto-oligosaccharides and 2'-fucosyllactose reduce necrotising enterocolitis in neonatal rats. Br J Nutr. 2016;116(2):294-9.

22. Weichert S, Jennewein S, Hüfner E, Weiss C, Borkowski J, Putze J, Schroten H. Bioengineered 2'-fucosyllactose and 3-fucosyllactose inhibit the adhesion of Pseudomonas aeruginosa and enteric pathogens to human intestinal and respiratory cell lines. Nutr Res. 2013;33(10):831-8.

23. Marriage BJ, Buck RH, Goehring KC, Oliver JS, Williams JA. Infants fed a lower calorie formula with 2’FL show growth and 2’FL uptake like breast-fed infants. J Pediatr Gastroenterol Nutr. 2015;61(6):649-58.

24. Kajzer J, Oliver J, Marriage B. Gastrointestinal tolerance of formula supplemented with oligosaccharides. FASEB J. 2016; 30(1Supp):671.4.

25. Buck R, Goehring K, Marriage B, Oliver J, Wilder J, Barrett E. Novel approaches to the elucidation of HMO biological effects. Abstract presented at FASEB SRC 2015.

©2016 Abbott Laboratories 161586/August 2016 LITHO IN USA

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