Skip to main content
Log in

Metabolic fate of milk glycosaminoglycans in breastfed and formula fed newborns

  • Original Article
  • Published:
Glycoconjugate Journal Aims and scope Submit manuscript

Abstract

In this study, the content, structure and residual percentages of glycosaminoglycans (GAGs) in the feces of seven breastfed newborns after ingesting a known amount of milk were studied. A comparison was made with five newborns fed with formula milk. Characterization of GAGs from milk and feces samples was performed according to previous methodology. Compared to the ingested GAGs present in milk, residual feces GAGs of breastfed newborns were <0.4 %, contrary to formula milk fed children, where the residues were ~4 %. As a consequence, >99 % of human milk GAGs are utilized as opposed to ~96 % of formula milk. Hyaluronic acid utilization was found to be fairly similar contrary to chondroitin sulfate/dermatan sulfate and heparan sulfate, which were found to be ~10–18 times lower in formula milk fed children. Our new results further demonstrate that the elevated content of human milk GAGs passes undigested through the entire digestive system of newborns, possibly protecting the infant from infections. In the distal gastrointestinal tract, these complex macromolecules are catabolized by a cohort of bacterial enzymes and constituent monosaccharides/oligosaccharides utilized for further metabolic purposes potentially useful for bacteria metabolism or internalized by intestinal cells. Thanks to their elevated structural heterogeneity, milk GAGs are used differently depending on their distinct primary structure. Finally, a different utilization and availability was observed for human milk GAGs compared to formula milk due to their various composition and structural heterogeneity.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Hamosh M.: Bioactive factors in human milk. Pediatr. Clin. N. Am. 48, 69–86 (2001)

    Article  CAS  Google Scholar 

  2. Morrow A.L., Ruiz-Palacios, Jiang X.: Newburg DS. Human milk glycans that inhibit pathogen binding protect breast-fed infants against infectious diarrhea. J. Nutr. 135, 1304–1307 (2005)

    CAS  PubMed  Google Scholar 

  3. Hanson L.A.: Feeding and infant development breast-feeding and immune function. Proc. Nutr. Soc. 66, 384–396 (2007)

    Article  CAS  PubMed  Google Scholar 

  4. Newburg D.S.: Neonatal protection by an innate immune system of human milk consisting of oligosaccharides and glycans. J. Anim. Sci. 87, 26–34 (2009)

    Article  CAS  PubMed  Google Scholar 

  5. Newburg D.S., Linhardt R.J., Ampofo S.A., Yolken R.H.: Human milk glycosaminoglycans inhibit HIV glycoprotein gp120 binding to its host cell CD4 receptor. J Nutrition. 125, 419–424 (1995)

    CAS  Google Scholar 

  6. Coppa G.V., Gabrielli O., Buzzega D., Zampini L., Galeazzi T., Maccari F., Bertino E., Volpi N.: Composition and structure elucidation of human milk glycosaminoglycans. Glycobiology. 21, 295–303 (2011)

    Article  CAS  PubMed  Google Scholar 

  7. Coppa G.V., Gabrielli O., Zampini L., Galeazzi T., Maccari F., Buzzega D., Galeotti F., Bertino E., Volpi N.: Glycosaminoglycan content in term and preterm milk during the first month of lactation. Neonatology. 101, 74–76 (2012)

    Article  CAS  PubMed  Google Scholar 

  8. Coppa G.V., Gabrielli O., Zampini L., Bertino E., Volpi N.: Human milk glycosaminoglycans as possible bioactive substances for the breastfed newborn. Breastfeed. Med. 8, 227 (2013)

    Article  PubMed  Google Scholar 

  9. Coscia A., Peila C., Bertino E., Coppa G.V., Moro G.E., Gabrielli O., Zampini L., Galeazzi T., Maccari F., Volpi N.: Effect of holder pasteurisation on human milk glycosaminoglycans. J. Pediatr. Gastroenterol. Nutr. 60, 127–130 (2015)

    Article  CAS  PubMed  Google Scholar 

  10. Jackson R.J., Busch S.J., Cardin A.D.: Glycosaminoglycans: molecular properties, protein interactions, and role in physiological processes. Physiol. Rev. 71, 481–539 (1991)

    CAS  PubMed  Google Scholar 

  11. Gesslbauer B., Theuer M., Schweiger D., Adage T., Kungl A.J.: New targets for glycosaminoglycans and glycosaminoglycans as novel targets. Expert Rev Proteomics. 10, 77–95 (2013)

    Article  CAS  PubMed  Google Scholar 

  12. Gandhi N.S., Mancera R.L.: Heparin/heparan sulphate-based drugs. Drug Discov. Today. 15, 1058–1069 (2010)

    Article  CAS  PubMed  Google Scholar 

  13. Coppa GV, Facinelli B, Magi G, Marini E, Zampini L, Mantovani V, Galeazzi T, Padella L, Marchesiello RL, Santoro L, Coscia A, Peila C, Volpi N, Gabrielli O. Human Milk Glycosaminoglycans Inhibit in vitro the Adhesion of Escherichia coli and Salmonella fyris to Human Intestinal Cells. Ped Res In Press (2016).

  14. Hill D.R., Rho H.K., Kessler S.P., Amin R., Homer C.R., McDonald C., Cowman M.K., de la Motte C.A.: Human milk hyaluronan enhances innate defense of the intestinal epithelium. J. Biolumin. Chemilumin. 288, 29090–29104 (2013)

    CAS  Google Scholar 

  15. Volpi N.: High-performance liquid chromatography and on-line mass spectrometry detection for the analysis of chondroitin sulfates/hyaluronan disaccharides derivatized with 2-aminoacridone. Anal. Biochem. 397, 12–23 (2010)

    Article  CAS  PubMed  Google Scholar 

  16. Volpi N., Galeotti F., Yang B., Linhardt R.J.: Analysis of glycosaminoglycan-derived, precolumn, 2-aminoacridone-labeled disaccharides with LC-fluorescence and LC-MS detection. Nat. Protoc. 9, 541–558 (2014)

    Article  CAS  PubMed  Google Scholar 

  17. Galeotti F., Volpi N.: Online reverse phase-high-performance liquid chromatography-fluorescence detection-electrospray ionization-mass spectrometry separation and characterization of heparan sulfate, heparin, and low-molecular weight-heparin disaccharides derivatized with 2-aminoacridone. Anal. Chem. 83, 6770–6777 (2011)

    Article  CAS  PubMed  Google Scholar 

  18. Barthe L., Woodley J., Lavit M., Przybylski C., Philibert C., Houin G.: In vitro intestinal degradation and absorption of chondroitin sulfate, a glycosaminoglycan drug. Arzneimittelforschung. 54, 286–292 (2004)

    CAS  PubMed  Google Scholar 

  19. Larsen A.K., Lund D.P., Langer R., Folkman J.: Oral heparin results in the appearance of heparin fragments in the plasma of rats. Proc. Natl. Acad. Sci. U. S. A. 83, 2964–2968 (1986)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Dawes J., Hodson B.A., Pepper D.S.: The absorption, clearance and metabolic fate of dermatan sulphate administered to man. Studies using a radioiodinated derivative. Thromb Haemost. 62, 945–949 (1989)

    CAS  PubMed  Google Scholar 

  21. Volpi N.: Oral bioavailability of chondroitin sulfate (Condrosulf) and its constituents in healthy male volunteers. Osteoarthr. Cartil. 10, 768–777 (2002)

    Article  CAS  PubMed  Google Scholar 

  22. Volpi N.: Oral absorption and bioavailability of ichthyic origin chondroitin sulfate in healthy male volunteers. Osteoarthr. Cartil. 11, 433–441 (2003)

    Article  CAS  PubMed  Google Scholar 

  23. Du J., White N., Eddington N.D.: The bioavailability and pharmacokinetics of glucosamine hydrochloride and chondroitin sulfate after oral and intravenous single dose administration in the horse. Biopharm. Drug Dispos. 25, 109–116 (2004)

    Article  CAS  PubMed  Google Scholar 

  24. Ahn M.Y., Shin K.H., Kim D.H., Jung E.A., Toida T., Linhardt R.J., Kim Y.S.: Characterization of a Bacteroides species from human intestine that degrades glycosaminoglycans. Can. J. Microbiol. 44, 423–429 (1998)

    Article  CAS  PubMed  Google Scholar 

  25. Hong S.W., Kim B.T., Shin H.Y., Kim W.S., Lee K.S., Kim Y.S., Kim D.H.: Purification and characterization of novel chondroitin ABC and AC lyases from Bacteroides stercoris HJ-15, a human intestinal anaerobic bacterium. Eur. J. Biochem. 269, 2934–2940 (2002)

    Article  CAS  PubMed  Google Scholar 

  26. Shaya D., Hahn B.S., Park N.Y., Sim J.S., Kim Y.S., Cygler M.: Characterization of chondroitin sulfate lyase ABC from Bacteroides thetaiotaomicron WAL2926. Biochemistry. 47, 6650–6661 (2008)

    Article  CAS  PubMed  Google Scholar 

  27. Hyun Y.J., Lee K.S., Kim D.H.: Cloning, expression and characterization of acharan sulfate-degrading heparin lyase II from Bacteroides stercoris HJ-15. J. Appl. Microbiol. 108, 226–235 (2010)

    Article  CAS  PubMed  Google Scholar 

  28. Hyun Y.J., Lee J.H., Kim D.H.: Cloning, overexpression, and characterization of recombinant heparinase III from Bacteroides stercoris HJ-15. Appl. Microbiol. Biotechnol. 86, 879–890 (2010)

    Article  CAS  PubMed  Google Scholar 

  29. Hyun Y.J., Jung I.H., Kim D.H.: Expression of heparinase I of Bacteroides stercoris HJ-15 and its degradation tendency toward heparin-like glycosaminoglycans. Carbohydr. Res. 359, 37–43 (2012)

    Article  CAS  PubMed  Google Scholar 

  30. Ulmer J.E., Vilén E.M., Namburi R.B., Benjdia A., Beneteau J., Malleron A., Bonnaffé D., Driguez P.A., Descroix K., Lassalle G., Le Narvor C., Sandström C., Spillmann D., Berteau O.: Characterization of Glycosaminoglycan (GAG) Sulfatases from the Human Gut Symbiont Bacteroides thetaiotaomicron Reveals the First GAG-specific Bacterial Endosulfatase. J. Biolumin. Chemilumin. 289, 24289–24303 (2014)

    CAS  Google Scholar 

  31. Benno Y., Sawada K., Mitsuoka T.: The intestinal microflora of infants: composition of fecal flora in breast-fed and bottle-fed infants. Microbiol. Immunol. 28, 975–986 (1984)

    Article  CAS  PubMed  Google Scholar 

  32. Balmer S.E., Wharton B.A.: Diet and faecal flora in the newborn: breast milk and infant formula. Arch. Dis. Child. 64, 1672–1677 (1989)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Volpi N., Gabrielli O., Carlucci A., Zampini L., Santoro L., Padella L., Marchesello R.L., Maccari F., Coppa G.V.: Human milk glycosaminoglycans in feces of breastfed newborns: preliminary structural elucidation and possible biological role. Breastfeed. Med. 9, 105–106 (2014)

    Article  PubMed  Google Scholar 

  34. Simon-Assmann P., Kedinger M., De Arcangelis A., Rousseau V., Simo P.: Extracellular matrix components in intestinal development. Experientia. 51, 883–900 (1995)

    Article  CAS  PubMed  Google Scholar 

  35. Jandik K.A., Kruep D., Cartier M., Linhardt R.J.: Accelerated stability studies of heparin. J. Pharm. Sci. 85, 45–51 (1996)

    Article  CAS  PubMed  Google Scholar 

  36. Volpi N., Mucci A., Schenetti L.: Stability studies of chondroitin sulfate. Carbohydr. Res. 315, 345–349 (1999)

    Article  CAS  PubMed  Google Scholar 

Download references

Contributors

N.V. developed the applied methodologies. F.M., V.M., L.Z., T.G. and F.G. performed the experimental procedures and analyses. A.C. collected the feces samples. N.V., G.V.C. and O.G. designed and developed the experimental design, performed data analysis and wrote the manuscript.

All authors reviewed and approved the study.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Nicola Volpi.

Ethics declarations

Conflicts of interest

We declare that we have no conflicts of interest.

Grant support

None.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Maccari, F., Mantovani, V., Gabrielli, O. et al. Metabolic fate of milk glycosaminoglycans in breastfed and formula fed newborns. Glycoconj J 33, 181–188 (2016). https://doi.org/10.1007/s10719-016-9655-5

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10719-016-9655-5

Keywords

Navigation