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Classification, Structure, and Bioactive Functions of Oligosaccharides in Milk
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 Title & Authors
Classification, Structure, and Bioactive Functions of Oligosaccharides in Milk
Mijan, Mohammad Al; Lee, Yun-Kyung; Kwak, Hae-Soo;
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Milk oligosaccharides are the complex mixture of six monosaccharides namely, D-glucose, D-galactose, N-acetyl-glucosamine, N-acetyl-galactosamine, L-fucose, and N-acetyl-neuraminic acid. The mixture is categorized as neutral and acidic classes. Previously, 25 oligosaccharides in bovine milk and 115 oligosaccharides in human milk have been characterized. Because human intestine lacks the enzyme to hydrolyze the oligosaccharide structures, these substances can reach the colon without degradation and are known to have many health beneficial functions. It has been shown that this fraction of carbohydrate can increase the bifidobacterial population in the intestine and colon, resulting in a significant reduction of pathogenic bacteria. The role of milk oligosaccharides as a barrier against pathogens binding to the cell surface has recently been demonstrated. Milk oligosaccharides have the potential to produce immuno-modulation effects. It is also well known that oligosaccharides in milk have a significant influence on intestinal mineral absorption and in the formation of the brain and central nervous system. Due to its structural resemblance, bovine milk is considered to be the most potential source of oligosaccharides to produce the same effect of oligosaccharides present in human milk. This review describes the characteristics and potential health benefits of milk oligosaccharides as well as the prospects of oligosaccharides in bovine milk for use in functional foods.
oligosaccharide;bovine milk;bioactive function;classification;
 Cited by
Milk Inhibits the Biological Activity of Ricin, Journal of Biological Chemistry, 2012, 287, 33, 27924  crossref(new windwow)
Barile, D., Marotta, M., Chu, C., Mehra, R., Grimm, R., Lebrilla, C. B., and German, J. B. (2010) Neutral and acidic oligosacchrarides in Hostein-Friesian colostrums during the first 3 days of lactation measured by high performance liquid chromatography on a microfluidic chip and time-of-flight mass spectrometry. J. Dairy Sci. 93, 3940-3949. crossref(new window)

Barile, D., Tao, N., Lebrilla, C. B., Coisson. J-D., Arlorio, M., and German, J. B. (2009) Permeate from cheese whey ultrafiltration is a source of milk oligosaccharides. Int. Dairy J. 19, 524-530. crossref(new window)

Bode, L. (2006) Recent advances on structure, metabolism and function of human milk oligosaccharides. J. Nutr. 136, 2127-2130.

Bode, L., Kunz, C., Muhly-Reinholz, M., Mayer, K., Seeger, W., and Rudloff, S. (2004a) Inhibition of monocyte, lymphocyte and neutrophil adhesion to endothelial cells by human milk oligosaccharides. J. Throm. Haemost. 92, 1402-1410.

Bode, L., Rudloff, S., Kunz, C., Strobel, S., and Klein, N. (2004b) Human milk oligosaccharides reduce platelet-neutrophil complex formation leading to a decrease in neutrophil beta 2 integrin expression. J. Leukocyte Biol. 76, 820-826. crossref(new window)

Boehm, G. and Moro, G. (2008) Structural and functional aspects of prebiotics used in infant nutrition. J. Nutr. 138, 1818S-1828S.

Boehm, G. and Stahl, B. (2007) Oligosaccharides from milk. J. Nutr. 137, 847S-849S.

Boehm, G. and Stahl, B. (2003) Oligosachardes. In: Functional dairy products. Mattila-Sandholm, T. (ed) Woodhead publishers, Cambridge, UK, pp. 203-243.

Bogoch, S. (1977) Recognins and their chemoreciprocals. In: Behavioural neurochemistry. DeFeudis, F. V., and Delgado, J. M. (eds) Spectrum Publishers, New York, NY, USA, p. 270.

Carden, D. L. and Granger, D. N. (2000) Pathophysiology of ischaemia-reperfusion injury. J. Pathol. 190, 255-266. crossref(new window)

Chonan, O. and Watanuki, M. (1996) The effect of 6'-galactooligosaccharides on bone mineralization of rats adapted to different levels of dietary calcium. Int. J. Vitam. Nutr. 66, 244-249.

Coppa, G. V., Zampini, L., Galeazzi, T., and Gabrielli, O. (2006) Prebiotics in human milk: a review. Digest. Liver Dis. 38, S291-S294. crossref(new window)

Coppa, G. V., Pierani, P. Zampini, L., Bruni, S., Carloni, I., and Gabrielli O. (2001) Characterization of oligosaccharides in milk and feces of breast-fed infants by high performance anion-exchange chromatography. Adv. Med. Biol. 501, 307-314. crossref(new window)

Cumar, F. A., Ferchmin, P. A., and Caputto, R. (1965) Isolation and identification of a lactose phosphatase ester from cow colostrums. Biochem. Biophys. Res. Comm. 20, 60-62. crossref(new window)

Fergusson, D. M., Beautrais, A. L., and Silva, P. (1982) Breastfeeding and cognitive development in the first seven years of life. Soc. Sci. Med. 16, 1705-1708. crossref(new window)

Gibson, G. and Roberfroid, M. (1995) Dietary modulation of human colonic microbiota-introducing the concept of probiotics. J. Nutr. 125, 1401-1412.

Gopal, P. K. and Gill, H. S. (2000) Oligosaccharides and glycoconjugates in bovine milk and colostrums. Brit. J. Nutr. 84, 69-74.

Gronlund, M. M., Lehtonen, O. P., Eerola, E., and Kero, P. (1999) Fecal microflora in healthy infants born by different methods of delivery: permanent changes in intestinal flora after caesarean delivery. J. Pediat. Gastroenterol. Nutr. 28, 19-25. crossref(new window)

Gruber, C., van Stuijvenberg M., Mosca, F., Moro, G., Chirico, G., Braegger, C. P., Riedler, J., Boehm, G., and Wahn, U. (2010) Reduced occurrence of early atopic dermatitis because of immunoactive prebiotics among low-atopy-risk infants. J. Alergy Clin. Immunol. 126, 791-797. crossref(new window)

Hakkarainen, J., Toaiven, M., Leinonen, A., Frangsmyr, L., Stromberg, N., Lapinjoki, S., Nasssif, X., and Tikkanen-Kaukanen, C. (2005) Human and bovine milk oligosaccharides inhibit Neisseria meningitidis pili attachment in vitro. J. Nutr. 135, 2445-2448.

Heuvel van den E. G., Schoteraman, M. H., and Muijs, T. (2000) Transgalacto-oligosaccharides stimulate calcium absorption in postmenopausal women. J. Nutr. 130, 2938-2942.

Heuvel van den E. G., Schaafsma G., Muys T., and Dokkum van, W. (1998) Non digestible oligosaccharides do not interfere with calcium and nonhem-iron absorption in young, healthy men. Am. J. Clin. Nutr. 67, 445-451.

IUPAC/IUBMB (1997) Joint Commission on Biochemical Nomenclature (JCBN) Nomenclature of Carbohydrates, Recommendations 1996. Carbohydr. Res. 297, 1-90. crossref(new window)

Johansson, P., Nilsson, J., Angstrom, J., and Meller-Podraza, H. (2005) Interaction of Helicobacter pylori with sialylated carbohydrates: the dependence on different parts of the binding trisaccharides $Neu5Ac{\alpha}3Gal{\beta}4GlcNAc$. Glycobiol. 15, 625-636.

Jungi, T. W., Spycher, M. O., Nydegger, U. E., and Barandun, S. (1986) Platelet-leukocyte interaction: selective binding of thrombin-stimulated platelets to human monocytes, polymorphonuclear leukocyte, and related cell lines. Blood 67, 629-636.

Kimura, K., Watanabe, Y., Matsumoto, K., and Miyagi, A. (1997) Yakult Reports 17, 1-7.

Kuhn, R., and Gauhe, A. (1965) Bestimmung der bindungsstellen von sialinsaure-resten in oligosacchariden mit hilfe von perjodat. Chem. Ber. 98, 395-413. crossref(new window)

Kobata, A. (2010) Structures and application of oligosaccharides in human milk. Proc. Jpn. Acad., Ser. B. 86, 731-747. crossref(new window)

Kobata, A., Grollman, E. F., Torain, B. F., and Ginsburg, V. (1970) Blood and tissue antigens. Academic press, New York, USA, pp. 497.

Kunz, C. and Rudloff, S. (2006) Health promoting aspects of milk oligosaccharides. Int. Dairy J. 16, 1341-1346. crossref(new window)

Kunz, C., Rudloff, S., Baier, W., Klein, N., and Strobel, S. (2000) Oligosaccharides in human milk. Structural, functional, and metabolic aspects. Annu. Rev. Nutr. 20, 699-722. crossref(new window)

Lucas, A., Morley, R., Cole, T. J., Lister, G., and Leeson-Payne, C. (1992) Breast milk and subsequent intelligence quotient in children born preterm. Lancet 339, 261-264. crossref(new window)

Manning, T. S., and Gibson, G. R. (2004) Prebiotics. Best Prac. Res. Clin. Gastro. 18, 287-298. crossref(new window)

Martinez-Ferez, A., Rudloff, S., Guadix, A., Henkel, C. A., Phlents, G., Boza, J. J., Guadix, E. M., and Kunz, C. (2006) Goats' milk as a natural source of lactose-derived oligosaccharides: Isolation by membrane technology. Int. Dairy J. 16, 173-174. crossref(new window)

Martin, M. J., Martin-Sosa, S., and Hueso, P. (2002) Binding of milk oligosaccharides by several enterotoxigenic Eschecrichia coli strains isolated from calves. Glycoconj. J. 19, 5-11.

Martin, M. J., Marin-Sosa., S. Garcia-Pardo, L. A., and Hueso, P. (2001) Distribution of bovine sialoglycoconjugates during lactation. J. Dairy Sci. 84, 995-1000. crossref(new window)

Maslowski, K. M., Vieira, A. T., Ng, A., Kranich, J., Sierro, F., Yu, D., Schilter, H. C., Rolph, M. S., Mackay, F., Artis, D., Xavier, R. J., Teixeira, M. M., and Mackay, C. R. (2009) Regulation of inflammatory responses by gut microbiota and chemoattractant receptor GPR43. Nature 461, 1282-1286. crossref(new window)

McEver, R. P. (1997). Selectin-carbohydrate interactions during inflammation and metastasis. Glycoconj. J. 14, 585-591. crossref(new window)

Mehra, R., and Kelly, P. (2006) Milk oligosaccharides: structural and technological aspects. Int. Dairy J. 16, 1334-1340. crossref(new window)

Mills, S., Ross, R. P., Hill, C., Fitzgerald, G. F., and Stanton, C. (2011) Milk intelligence: Mining milk of bioactive substances associated with human health. Int. Dairy J. 21, 382-386.

Monchois, V., Willemot, R. M., and Monsan, P. (1999) Glucansucrases: Mechanism of action and structure-function relationships. FEMS Microbiol. Rev. 23, 131-151.

Mussatto, S. I., and Manchilha, I. M. (2007) Non-digestible oligosaccharides: A review. Carbohydr. Polymers 68, 587-597. crossref(new window)

Nakamura, T., Kawase, H., Kimura, K., Watanabe, Y., Ohtani, M., Arai, I., and Urashima, T. (2003) Concentrations of sialyloligosaccharides in bovine colostrums and milk during the prepartum and early lactation. J. Dairy Sci. 86, 1315-1320. crossref(new window)

Newburg, D. S. (1999) Human milk glycocnjugates that inhibit pathogens. Curr. Med. Chem. 6, 117-127.

Ngo, D.-N., Kim, M.-M., and Km, S.-K. (2008) Chitin oligosaccharides inhibit oxidative stress in live cells. Carbohyd. Polym. 74, 228-234. crossref(new window)

Niess, J. H., Brand, S., Gu, X., Landsman, L., Jung, S., McCormick, B. A., Vyas, J. M., Boes, M., Ploegh, H. L., Fox, J. G., Littman, D. R., and Reinecker, H. C. (2005) $CX_{3}CR1$-mediated dendritic cell access to the intestinal lumen and bacterial clearance. Science 307, 254-258. crossref(new window)

Ninonuevo, M. R., Park, Y., Yin, H., Zhang, J., Ward, R. E., Clowers, B. H., German, J. B., Freeman S. L., Killeen, K., Grimm, R., and Lebrilla, C. B. (2006) A strategy for annotating the human milk glycome. J. Agric. Food Chem. 54, 7471-7480. crossref(new window)

Parkkinen, J., and Finne, J. (1987) Isolation of sialyl oligosaccharides and sialyl oligosaccharide phosphates from bovine colostrums and human urine. In: Methods in Enzymology Ginsberg, V. (ed) Academic Press, New York. Vol. 138, pp. 289-300.

Peters, M. J., Dixon, G., Kotowicz, K. T., Hatch, D. J., Heyderman, R. S., and Klein, N. J. (1999) Circulating plateletneutrophil complexes represent a subpopulation of activated neutrophils primed for adhesion, phagocytosis and intracellular killing. Brit. J. Haematol. 106, 391-399. crossref(new window)

Qiang, X., YongLie, C., and QiaBing, W. (2009) Health benefit application of functional oligosaccharides. Carbohyd. Polym. 77, 435-441. crossref(new window)

Rescigno, M. and Di Sabatino, A. (2009) Dendritic cells in intestinal homeostasis and disease. J. Clin. Invest. 119, 2441-2450. crossref(new window)

Rivero-Urgell M., and Santamaria-Orleans, A. (2001) Oligosaccharides: application in infant food. Early Human Develop. 65, S43-S45. crossref(new window)

Rousseu, V., Lepargneur, J. P., Roques, C., Remaud-Simeon, M., and Paul, F. (2005) Prebiotic effects of oligosaccharides on selected vaginal lactobacilli and pathogenic microorganisms. Anaerobe 11, 145-153. crossref(new window)

Rudloff, S., Phlentz, G., Diekmann, L., Egge, H., and Kunz, C. (1996) Urinary excretion of lactose and oligosaccharides n preterm infants fed human milk or infant formula. Acta Paedeatr. 85, 598-603. crossref(new window)

Ruiz-Palacios, G. M., Cervantes, L. E., Ramos, P., Chavez- Munguia, B., and Newburg, D. S. (2003) Campylobacter jejuni binds intestinal H(O) antigen ($Fuc{\alpha}1,\;2\;Gal{\beta}1,4$ GlcNAc), and fucosyloligosaccharides of human milk inhibit its binding and infection. J. Biol. Chem. 278, 14112-14120. crossref(new window)

Sabharwal, H., Sjoblad, S., and Lundblad, A. (1991) Affinity chromatographic identification and quantification of blood group A-active oligosaccharides in human milk and feces of breast-fed infants. J. Pediatr. Gastroenterol. Nutr. 12, 474-479. crossref(new window)

Saito, T., Itoh, T., and Adachis, S. (1987) Chemical structure of three neutral trisaccharides isolated in free form from bovine colostrums. Carbohydr Res. 165, 43-51. crossref(new window)

Saito, T., Itoh, T., and Adachi, S. (1984) Presence of two neutral disaccharides containing N-acetylhexosamine in bovine colostrums as free forms. Biochem. Biophys. Acta 801, 147-150. crossref(new window)

Schaur, R., and Kamerling, J. P. (1997) Chemistry, biochemistry and biology of sialic acids. In: Glycoproteins II, Schachter, H., Montreuil, and Vilegenthart, J. F. G. (eds) Elsvier, Amsterdam, The Netherlands, pp. 243-372.

Scheneir, M. L. and Rafelson, M. E. (1996) Isolation of two structural isomers of N-acetylneuraminyllactose from bovine colostrum. Biochem. Biophys. Acta 130, 1-11.

Schimdt, R. (1989) Glycoproteins involved in long-lasting plasticity in the teleost brain. Forts. Zool. 37, 327-339.

Scholz-Ahrens, K., Schsafsma, G., Van Del Heuvel E. G. M. J., and Schrezenmeir J (2001) Effect of Prebiotics in mineral metabolism. Am. J. Clin. Nutr. 73, 459S-464S.

Schon, M. P., Krahn, T., Schon, M., Rodriquez, M. -L., Antonicek, H., Schultz, J. E., Ludwiq, R. J., Zollner, T. M., Bischoff, E., Bremm, K. D., Schramm, M., Henninger, K., Kaufmann, R., Gollnick, H. P. Parker, C. M., and Boenchke, W. H. (2002) Efomycine M, a new specific inhibitor of selectin, impairs leukocyte adhesion and alleviates cutaneous inflammation. Nature Med. 8, 366-372. crossref(new window)

Schumacher, G., Bendas, G., Stahl, B., and Beermann, C. (2006) Human milk oligosaccharides affect P-selectin binding capacities: in vitro investigation. Nutr. 22, 620-627. crossref(new window)

Schwertmann, A., Rudloff, S., and Kunz, C. (1996) Potential ligands for cell adhesion molecules in human milk. Ann. Nutr. Metab. 40, 252-262. crossref(new window)

Smith, M. M., Durkin, M., Hinton, V. J., Bellinger, D., and Kuhn, L. (2003) Influence of breastfeeding on cognitive outcomes at age 6-8 years: follow-up of very low birth weight infants. Am. J. Epidem. 158, 1075-1082. crossref(new window)

Tao, N., DePeters, E. J., Freeman, S. German, J. B., Grimm, R., and Lebrilla, C. B. (2009) Variations in bovine milk oligosaccharides during early and middle lactation stages analyzed by high-performance liquid chromatography-chip/mass spectrometry. J. Dairy Sci. 92, 2991-3001. crossref(new window)

Tao, N., DePeters, E. J., Freeman, S., German, J. B., Grimm, R., and Lebrilla, C. B. (2008) Bovine milk glycome. J. Dairy Sci. 91, 3768-3778. crossref(new window)

Urashima, T. and Taufik, T. (2010) Oligosaccharides in milk: Their benefits and future utilization. J. Anim. Sci. Technol. 33, 189-197. crossref(new window)

Urashima, T., Saito, T., Nakamura, T., and Messer, M. (2001) Oligosaccharides of milk and colostrums in non-human mammals. Glycoconj. J. 18, 357-371. crossref(new window)

Urashima, T., Saito, T., and Nakamura, T. (1997b) Structural determination of mono-sialyltrisaccharides obtained from caprine colostrum. Comp. Biochem. Physiol. 116, 431-435. crossref(new window)

Urashima, T., Bubb, W. A., Messer, M., Tsujii, Y., and Taneda, Y. (1994) Studies of the neutral trisaccharides of goat (Capra hircus) and of the one- and two-dimensional $^{1}H\;and\;^{13}C$ NMR spectra of 6'-N-acetylglucosaminyllactose. Carbhydr. Res. 269, 173-184.

Urashima, T., Saitu, T., and Kimura, T. (1991b) Structural determination of three neutral oligosaccharides in bovine (Holstein-Friesian) colostrum. Comp. Biochem. Biophys. Acta 1073, 225-229. crossref(new window)

Veh, R. W., Michalski, J. C., Corfield, A. P., Sander-Wewer, M., Gies, D., and Schauer, R. (1981) New chromatographic system for the rapid analysis and preparation of colostrum sialyloligosaccharides. J. Chromatogr. 212, 313-322. crossref(new window)

Viverge, D., Grimmonprez, L., and Solere, M. (1997) Chemical characterization of sialyl oligosaccharides isolated from goat (capra hircus) milk. Biochem. Biophys. Acta 1336, 157-164. crossref(new window)

Von Itzstein, M. and Thomson, R. J. (1997) Sialic acid and sialic acid-recognizing proteins: drug discovery targets and potential glycopharmaceuticals. Curr. Med. Chem. 4, 185-210.

Wang, B., Yu, B., Karim, M., Hu, H., Sun, Y., McGreevy, P., et al. (2007b) Dietary sialic acid supplementation improves learning and memory in piglets. Am. J. Clin. Nutr. 85, 561-569.

Wang, B. and Brand-Miller, J. (2003) The role and potential of sialic acid in human nutrition. Eur. J. Clin. Nutr. 57, 1351-1369. crossref(new window)

Zivkovic, A. M. and Barile, D. (2011) Bovine milk as a source of functional oligosaccharides for improving human health. Adv. Nutr. 2, 284-288. crossref(new window)