Skip to main content

Breast Milk Oligosaccharides

  • Chapter
  • First Online:
Breastfeeding and Metabolic Programming

Abstract

Oligosaccharides are polymeric molecules typically consisting of between three and around ten monosaccharide subunits. Human breast milk differs from that found in the majority of mammalian species by virtue of the rich mixture of oligosaccharides (at least 150 different types) that it contains at high levels. Human milk oligosaccharides (HMOs) in mature human milk are even more abundant than milk proteins. They are usually present at a concentration of 5–15 g/L, which means that, if the water content is disregarded, they are exceeded in amount only by disaccharide lactose and milk fats [1, 2].

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 119.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Bode L. Human milk oligosaccharides: structure and functions. Nestle Nutr Inst Workshop Ser. 2020;94:115–23. https://doi.org/10.1159/000505339. Epub 2020 Mar 11.

    Article  PubMed  Google Scholar 

  2. Bode L, Contractor N, Barile D, et al. Overcoming the limited availability of human milk oligosaccharides: challenges and opportunities for research and application. Nutr Rev. 2016;74:635–44.

    Article  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Azad MB, Robertson B, Atakora F, et al. Human milk oligosaccharide concentrations are associated with multiple fixed and modifiable maternal characteristics, environmental factors and feeding practices. J Nutr. 2018;148:1733–42.

    Article  PubMed  Google Scholar 

  5. Jantscher-Krenn E, Bode L. Structure-function relationships of human milk oligosaccharides. Adv Nutr. 2012;3:383S–91S.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Kumazaki T, Yoshida A. Biochemical evidence that secretor gene, Se, is a structural gene encoding a specific fucosyltransferase. Proc Natl Acad Sci U S A. 1984;81:4193–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Stahl B, Thurl S, Henker J, et al. Detection of four human milk groups with respect to Lewis-bloodgroup-dependent oligosaccharides by serologic and chromatographic analysis. Adv Exp Med Biol. 2001;501:299–306.

    Article  CAS  PubMed  Google Scholar 

  8. Ruhaak LR, Stroble C, Underwood MA, et al. Detection of milk oligosaccharides in plasma of infants. Anal Bioanal Chem. 2014;406:5775–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Rudloff S, Obermeier S, Borsch C, et al. Incorporation of orally applied (13)C-galactose into milk lactose and oligosaccharides. Glycobiology. 2006;16:477–87.

    Article  CAS  PubMed  Google Scholar 

  10. German JB, Freeman SL, Lebrilla CB, et al. Human milk oligosaccharides: evolution, structures and bioselectivity as substrates for intestinal bacteria. Nestlé Nutr Workshop Ser Pediatr Program. 2008;62:205–18; discussion 218–222.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Oftedahl OT. The evolution of milk secretion and its ancient origins. Animal. 2012;6:355–68.

    Article  Google Scholar 

  12. Lin AE, Autran CA, Szyszka A, et al. Human milk oligosaccharides inhibit growth of group B streptococcus. J Biol Chem. 2017;292:11,243–9.

    Article  CAS  Google Scholar 

  13. Ruiz-Palacios GM, Cervantes LE, Ramos P, et al. Campylobacter jejuni binds intestinal H (O) antigen (Fucα1,2Galβ1, 4GlcNAc), and fucosyloligosaccharides of human milk inhibit its binding and infection. J Biol Chem. 2003;278:1411214120.

    Article  Google Scholar 

  14. Morrow AL, Ruiz-Palacios GM, Altaye M, et al. Human milk oligosaccharides are associated with protection against diarrhea in breast-fed infants. J Pediatr. 2004;145:297–303.

    Article  CAS  PubMed  Google Scholar 

  15. Manthey CF, Autran CA, Eckmann L, Bode L. Human milk oligosaccharides protect against enteropathogenic E. coli attachment in vitro and colonization in suckling mice. J Pediatr Gastroenterol Nutr. 2014;58:167–70.

    Article  CAS  Google Scholar 

  16. LoCascio RG, Ninonuevo MR, Freeman SL, et al. Glycoprofiling of bifidobacterial consumption of human milk oligosaccharides demonstrates strain specific, preferential consumption of small chain glycans secreted in early human lactation. J Agric Food Chem. 2007;55:8914–9.

    Article  CAS  PubMed  Google Scholar 

  17. Ramani S, Stewart CJ, Laucirica DR, et al. Complex interplay between human milk oligosaccharides, milk microbiome and infant gut microbiome modulates neonatal rotavirus infection. Nat Commun. 2018;9:5010.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Alderete TL, Autran CA, Brekke BE, et al. Associations between human milk oligosaccharides and infant body composition in the first six months of life. Am J Clin Nutr. 2015;102:13811388.

    Article  Google Scholar 

  19. Larsson MW, Lind MV, Laursen RP, et al. Human milk oligosaccharide composition is associated with excessive weight gain during exclusive breastfeeding—an explorative study. Front Pediatr. 2019;7:297.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Jantscher-Krenn E, Aigner J, Reiter B, et al. Evidence of human milk oligosaccharides in maternal circulation already during pregnancy—a pilot study. Am J Physiol Endocrinol Metab. 2019;316:E347–57.

    Article  CAS  PubMed  Google Scholar 

  21. Donovan SM, Comstock SS. Human milk oligosaccharides influence neonatal mucosal and systemic immunity. Ann Nutr Metab. 2016;69(Suppl 2):42–51. https://doi.org/10.1159/000452818. Epub 2017 Jan 20.

    Article  PubMed  Google Scholar 

  22. Hester SN, Donovan SM. Individual and combined effects of nucleotides and human milk oligosaccharides on proliferation, apoptosisandnecrosis in a humanfetalintestinalcellline. Food Nutr Sci. 2012;3:1567–76.

    CAS  Google Scholar 

  23. Lane JA, O’Callaghan J, Carrington SD, Hickey RM. Transcriptional response of HT-29 intestinal epithelial cells to human and bovine milk oligosaccharides. Br J Nutr. 2013;110:2127–37.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  25. Bhatia S, Prabhu PN, Benefiel AC, Miller MJ, Chow J, Davis SR, Gaskins HR. Galacto-oligosaccharides may directly enhance intestinal barrier function through the modulation of goblet cells. Mol Nutr Food Res. 2015;59:566–73.

    Article  CAS  PubMed  Google Scholar 

  26. 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;65:33–46.

    Article  CAS  PubMed  Google Scholar 

  27. Mezoff EA, Hawkins JA, Ollberding NJ, Karns R, Morrow AL, Helmrath MA. The human milk oligosaccharide 2′-fucosyllactose augments the adaptive response to extensive intestinal resection. Am J Physiol Gastrointest Liver Physiol. 2016;310:G427–38.

    Article  PubMed  Google Scholar 

  28. Wise A, Robertson B, Choudhury B, et al. Infants are exposed to human milk oligosaccharides already in utero. Front Pediatr. 2018;6:270.

    Article  PubMed  PubMed Central  Google Scholar 

  29. 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 Microbiol. 2015;15:172.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Marcobal A, Sonnenburg JL. Human milk oligosaccharide consumption by intestinal microbiota. Clin Microbiol Infect. 2012;18(suppl 4):12–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Kavanaugh D, O’Callaghan J, Kilcoyne M, Kane M, Joshi L, Hickey RM. The intestinal glycome and its modulation by diet and nutrition. Nutr Rev. 2015;73:359–75.

    Article  PubMed  Google Scholar 

  32. Ewaschuk JB, Diaz H, Meddings L, Diederichs B, Dmytrash A, Backer J, Looijer-vanLangen M, Madsen KL. Secreted bioactive factors from Bifidobacterium infantis enhance epithelial cell barrier function. Am J Physiol Gastrointest Liver Physiol. 2008;295:1025–34.

    Article  Google Scholar 

  33. Macpherson AJ, Geuking MB, McCoy KD. Immune responses that adapt the intestinal mucosa to commensal intestinal bacteria. Immunology. 2005;115:153–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Comstock SS, Wang M, Hester SN, Li M, Donovan SM. Select human milk oligosaccharides directly modulate peripheral blood mononuclear cells isolated from 10-d-old pigs. Br J Nutr. 2014;111:819–28.

    Article  CAS  PubMed  Google Scholar 

  35. Goehring KC, Kennedy AD, Prieto PA, Buck RH. Direct evidence for the presence of human milk oligosaccharides in the circulation of breastfed infants. PLoS One. 2014;9:e101692.

    Article  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Ruhaak LR, Stroble C, Underwood MA, Le-brilla CB. Detection of milk oligosaccharides in plasma of infants. Anal Bioanal Chem. 2014;406:5775–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Bode L, Kunz C, Muhly-Reinholz M, Mayer K, Seeger W, Rudloff S. Inhibition of monocyte, lymphocyte, and neutrophil adhesion to endothelial cells by human milk oligosaccharides. Thromb Haemost. 2004;92:1402–10.

    Article  CAS  PubMed  Google Scholar 

  39. Bode L, Rudloff S, Kunz C, Strobel S, Klein N. Human milk oligosaccharides reduce platelet-neutrophil complex formation leading to a decrease in neutrophil beta 2 integrin expression. J Leukoc Biol. 2004;76:820–6.

    Article  CAS  PubMed  Google Scholar 

  40. Rabinovich GA, Croci DO. Regulatory circuits mediated by lectin-glycan interactions in autoimmunity and cancer. Immunity. 2012;36:322–35.

    Article  CAS  PubMed  Google Scholar 

  41. Schnaar RL. Glycans and glycan-binding proteins in immune regulation: a concise introduction to glycobiology for the allergist. J Allergy Clin Immunol. 2015;135:609–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Geijtenbeek TB, vanVliet SJ, Engering A, ‘tHart BA, van Kooyk Y. Self-and nonself-recognition by C-typel ectins on dendritic cells. Annu Rev Immunol. 2004;22:33–54.

    Article  CAS  PubMed  Google Scholar 

  43. Koning N, Kessen SF, Van Der Voorn JP, Appelmelk BJ, Jeurink PV, Knippels LM, Garssen J, Van Kooyk Y. Human milk blocks DC-SIGN-pathogen interaction via MUC1. Front Immunol. 2015;6:112.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Macauley MS, Crocker PR, Paulson JC. Si-glec-mediated regulation of immune cell function in disease. Nat Rev Immunol. 2014;14:653–66.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Stephenson HN, Mills DC, Jones H, Milioris E, Copland A, Dorrell N, Wren BW, Crocker PR, Escors D, Bajaj-Elliott M. Pseudaminic acid on Campylo bacterjejuni flagella modulates dendritic cell IL-10 expression via Si-glec-10 receptor: a novel flagellin-host interaction. J Infect Dis. 2014;210:1487–98.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Earl LA, Bi S, Baum LG. N-and O-glycans modulate galectin-1 binding, CD45 signaling, and T cell death. J BiolChem. 2010;285:2232–44.

    CAS  Google Scholar 

  47. Hester SN, Chen X, Li M, Monaco MH, Comstock SS, Kuhlenschmidt TB, Kuhlen-schmidt MS, Donovan SM. Human milk oligosaccharides inhibit rotavirus infectivity in vitro and in acutely infected piglets. Br J Nutr. 2013;110:1233–42.

    Article  CAS  PubMed  Google Scholar 

  48. Luhn K, Wild MK. Human deficiencies of fucosylation and sialylation affecting selectin ligands. Semin Immunopathol. 2012;34:383–99.

    Article  PubMed  Google Scholar 

  49. Castillo-Courtade L, Han S, Lee S, Mian FM, Buck R, Forsythe P. Attenuation of food allergy symptoms following treatment with human milk oligosaccharides in a mouse model. Allergy. 2015;70:1091–102.

    Article  CAS  PubMed  Google Scholar 

  50. Johnson PH, Watkins WM. Purification of the Lewis blood-group gene associated α-3/4fucosyltransferase from human milk: an enzyme transferring fucose primarily to type 1 and lactose-based oligosaccharide chains. Glycoconj J. 1992;9:241–9.

    Article  CAS  PubMed  Google Scholar 

  51. Seppo AE, Kukkonen AK, Kuitunen M, et al. Association of maternal probiotic supplementation with human milk oligosaccharide composition. JAMA Pediatr. 2019;173:286–8.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2023 The Author(s), under exclusive license to Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Şahin, Ö.N., Özpınar, A., Briana, D.D. (2023). Breast Milk Oligosaccharides. In: Şahin, Ö.N., Briana, D.D., Di Renzo, G.C. (eds) Breastfeeding and Metabolic Programming. Springer, Cham. https://doi.org/10.1007/978-3-031-33278-4_6

Download citation

  • DOI: https://doi.org/10.1007/978-3-031-33278-4_6

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-031-33277-7

  • Online ISBN: 978-3-031-33278-4

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics