Galacto-oligosaccharides and Other Products Derived from Lactose

  • M.J. Playne
  • R.G. Crittenden


Lactose is the precursor for a number of compounds derived by chemical, physical or enzymatic conversion that have an established and expanding place in the health and food industries. These include lactulose and galacto-oligosaccharides both of which are manufactured in large tonnages worldwide. Lactitol and lactosucrose are produced commercially, but in much smaller amounts, while lactobionic acid is produced for limited industrial and medical applications and for research use. The only other lactose derivative of commercial interest is an isomer of galactose called tagatose in which there is an emerging interest as a sweetener.


Dietary Fibre Hepatic Encephalopathy Intestinal Microbiota Glycaemic Index Basidiomycetous Yeast 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Ms Janet Werkmeister and staff of the Information Resource Centre, Dairy Australia, Melbourne and Ms Bee Thia of the CSIRO Ian Wark Laboratory are thanked for their bibliographic assistance.


  1. 3A Business Consulting. 2005. Global market analysis of whey and lactose products 2004–2009 (report published November 2005) J.M. Morks Gade 1, DK-8100 Aarhus C, Denmark.Google Scholar
  2. AACC. 2001. The definition of dietary fiber. Report of the Dietary Fiber Definition Committee to the Board of Directors of the American Association of Cereal Chemists. Cereal Foods World 46, 112–126.Google Scholar
  3. AACC. 2002. Method 32-33. Determination of trans-galacto-oligosaccharides in selected food products by ion- exchange chromatographic method. In: Approved Methods of the American Association of Cereal Chemists, 10th edition, p. 8.Google Scholar
  4. Abbadi, A., Gotlieb, K.F., Meiberg, J.B.M., Peters, J.A., Van Bekkum, H. 1999. New Ca-sequestering materials based on the oxidation of the hydrolysis products of lactose. Green Chem. 1, 231–235.CrossRefGoogle Scholar
  5. Adlerberth, I. 1999. Establishment of a normal intestinal microflora in the newborn infant. In: Probiotics, Other Nutritional Factors and Intestinal Microflora (L.A. Hansen, R.H. Yolken, eds.), pp. 63–78, Nestle Nutrition Workshop Series, Vol. 42, Nestec Ltd, Vevey. Lippincott-Raven, Philadelphia.Google Scholar
  6. Akiyama, K., Takase, M., Horikoshi, K., Okonogi, S. 2001. Production of galactooligosaccharides from lactose using a β-glucosidase from Thermus sp. Z-1 – recombinant production of thermostable β-glucosidase, purification, and use in galacto-oligosaccharide preparation, Biosci. Biotechnol. Biochem. 65, 438–441.CrossRefGoogle Scholar
  7. Alander, M., Matto, J., Kneifel, W., Johansson, M., Kogler, B., Crittenden, R., Mattila-Sandholm, T., Saarela, M. 2001. Effect of galacto-oligosaccharide supplementation on human faecal microflora and on survival and persistence of Bifidobacterium lactis Bb-12 in the gastrointestinal tract. Int. Dairy J. 11, 817–825.CrossRefGoogle Scholar
  8. Anon. 1997. Lactulose. Brochure of Morinaga Milk Industry Co., Ltd., Tokyo, Japan.Google Scholar
  9. Anon. 2003. Material Safety Data Sheet for Lactulose Concentrate, rev. 2, dated 18 Sept. 2003, Canlac Division of Solvay Pharma, Quebec, Canada.Google Scholar
  10. Asp, N.G., Burval, A., Dahlquist, A., Hallgren, P., Lundblad, A. 1980. Oligosaccharide formation during hydrolysis of lactose with Saccharomyces lactis lactase (Maxilact ®). II. Oligosaccharide structures. Food Chem. 5, 147–153.CrossRefGoogle Scholar
  11. AOAC International. 2006. Official Methods of Analysis, 18th edition revised. Method 2001.02.Google Scholar
  12. Bailey, R. (2008). Japan: An established market for nutraceuticals. Nutraceuticals World Nov. 2008.Google Scholar
  13. Bailey, R.W. 1965. Oligosaccharides, Pergamon Press, Oxford.Google Scholar
  14. Bakker-Zierikzee, A.M., Alles, M.S., Knol, J., Kok, F.J., Tolboom, J.J.M., Bindels, J.G. 2005. Effects of infant formula containing a mixture of galacto- and fructo-oligosaccharides or viable Bifidobacterium animalis on the intestinal microflora during the first 4 months of life. Br. J. Nutr. 94, 783–790.CrossRefGoogle Scholar
  15. Ballongue, J. 1998. Bifidobacteria and probiotic action. In: Lactic Acid Bacteria- Microbiology and Functional Aspects (S. Salminen, A. Von Wright, eds.), 2nd edition, Marcel Dekker, New York, pp. 519–587.Google Scholar
  16. Ballongue, J., Schumann, C., Quignon, P. 1997. Effects of lactulose and lactitol on colonic microflora and enzymatic activity. Scand. J. Gastroenterol. 32 Suppl. 222, 41–44.Google Scholar
  17. Beadle, J.R., Saunders, J. P., Wadja Jr., T.J. 1991. Process for manufacturing tagatose, US Patent 5,002,612. March 26, 1991. Assigned to Biospherics Inc.Google Scholar
  18. Beadle, J.R., Saunders, J.P., Wadja Jr., T.J. 1992. Process for manufacturing tagatose, US Patent 5,078,796. 7 January 1992. Assigned to Biospherics Inc.Google Scholar
  19. Benson, F.R. 1978. Sugar alcohols. In: Kirk-Othmer Encyclopaedia of Chemical Technology (E. Ecteroth, ed.), Vol. 1, 3rd Edition, pp. 754–778, Wiley, New York.Google Scholar
  20. Bertelsen, H., Andersen, H., Tvede, M. (2001). Fermentation of D-tagatose by human intestinal bacteria and dairy lactic acid bacteria. Microbial Ecol. Health Dis. 13, 87–95.CrossRefGoogle Scholar
  21. Bertelsen, H., Eriknauer, K., Bottcher, K., Christensen, J.S., Stougaard, P., Hansen, O.C., Jorgensen, F. 2006. Process for manufacturing of tagatose. US Patent 6,991,923 B2, issued Jan 31, 2006, assigned to Arla Foods Amba.Google Scholar
  22. Bertlesen, H., Jensen, B.B., Buemann, B. 1999. D-tagatose – a novel low-calorie bulk sweetener with prebiotic properties. World Rev. Nutr. Dietetics 85, 98–109.CrossRefGoogle Scholar
  23. Blum, S., Schiffrin, E. J. 2003. Intestinal microflora and homeostasis of the mucosal immune response: Implications for probiotic bacteria? Curr. Iss. Intest. Microbiol. 4, 53–60.Google Scholar
  24. Boehm, G., Stahl, B. 2003. Oligosaccharides. In: Functional Dairy Products (T. Mattila-Sandholm, M. Saarela, eds.), pp. 203– 243, Woodhead Publishing/CRC Press.Google Scholar
  25. Boehm, G., Stahl, B. 2007 Oligosaccharides from milk . J. Nutr., 137, Suppl 847S–849S.Google Scholar
  26. Boehm, G., Stahl, B., Jelinek, J., Knol, J., Miniello, V., Moro, G.E. 2005. Prebiotic carbohydrates in human milk and formulas. Acta Paed. 94 Suppl., 18–21.CrossRefGoogle Scholar
  27. Bolotin, A., et al. 2004. Complete sequence and comparative genome analysis of the dairy bacterium Streptococcus thermophilus. Nature Biotechnol. 22, 1554–1558.CrossRefGoogle Scholar
  28. Bongaerts, G., Severijnen, R., Timmerman, H. 2005. Effect of antibiotics, prebiotics and probiotics in treatment for hepatic encephalopathy. Med. Hypotheses 64, 64–68.CrossRefGoogle Scholar
  29. Booy, C.J. 1987. Lactitol – a New Food Ingredient. Bulletin 212, International Dairy Federation, Brussels, pp. 62–68.Google Scholar
  30. Bouhnik, Y., Raskine, L., Simoneau, G., Vicaut, E., Neut, C., Flourié, B., Brouns, F., Bornet, F. R. 2004a. The capacity of nondigestible carbohydrates to stimulate fecal bifidobacteria in healthy humans: a double-blind, randomized, placebo-controlled, parallel-group, dose-response relation study. Am. J. Clin. Nutr. 80, 1658–1664.Google Scholar
  31. Bouhnik, Y., Attar, A., Joly, F.A., Riottot, M., Dyard, F., Flourie B. 2004b. Lactulose ingestion increases faecal bifidobacterial counts: a randomised double-blind study in healthy humans. Eur. J. Clin. Nutr. 58, 462–466.CrossRefGoogle Scholar
  32. Bourlioux, P., Koletzko, B., Guarner, F., Braesco, V. 2003. The intestine and its microflora are partners for the protection of the host: report on the Danone Symposium “The Intelligent Intestine,” held in Paris, June 14, 2002. Am. J. Clin. Nutr. 78, 675–683.Google Scholar
  33. Bovee-Oudenhoven, I.M.J., Termont, D.M.S.L., Heidt, P.J., Van der Meer, R. 1997. Increasing the intestinal resistance of rats to the invasive pathogen Salmonella enteritidis: additive effects of dietary lactulose and calcium. Gut 40, 497–504.Google Scholar
  34. Brighenti, F., Benini, L., Del Rio, D., Casiraghi, C., Pellegrini, N., Scazzina, F., Jenkins, D.J.A., Vantini, I. 2006. Colonic fermentation of indigestible carbohydrates contributes to the second-meal effect. Am. J. Clin. Nutr. 83, 817–822.Google Scholar
  35. Bruzzese, E., Volpicelli, M., Squaglia, M., Tartaglione, A., Guarino, A. 2006. Impact of prebiotics on human health. Digest Liver Dis. 38 Suppl 2, S283–S287.CrossRefGoogle Scholar
  36. Burvall, A., Asp, N.G., Dahlquist, A. 1979. Oligosaccharide formation during hydrolysis of lactose with Saccharomyces lactis lactase (Maxilact ®) Part 1. Food Chem. 4, 243–250.CrossRefGoogle Scholar
  37. Camuesco, D., Peran, L., Comalada, M., Nieto, A., Di Stasi., L.C., Rodriguez-Cabezas, M.E., Concha, A., Zarzuelo, A., Galvez, J. 2005. Preventative effects of lactulose in the trinitrobenzenesulphonic acid model of rat colitis. Inflammatory Bowel Dis. 11, 265–271.CrossRefGoogle Scholar
  38. Carobbi, R., Bimbi, G., Cipolletti, G. 2001. Process for the preparation of a lactulose syrup by lactose isomerization. US Patent 6,214, 124, issued Aug 10, 2001, assigned to Inalco Spa.Google Scholar
  39. Carobbi, R., Miletti, S., Franci, V. 1985. Process for preparing lactulose from lactose, in the form of a syrup or a crystalline product. U.S. Pat. No. 4,536, 221, issued Aug. 20, 1985, assigned to SIRAC Spa.Google Scholar
  40. Carubelli, R. 1966. Transformation of disaccharides during borate ion-exchange chromatography. Isomerization of lactose into lactulose. Carbohydr. Res. 2, 480–485.CrossRefGoogle Scholar
  41. Challa, A., Rao, D.R., Chawan, C.B., Shackelford, L.1997. Bifidobacterium longum and lactulose suppress azoxymethane-induced colonic aberrant crypt foci in rats. Carcinogenesis 18, 517–521.CrossRefGoogle Scholar
  42. Chen, C., Li, L., Wu, Z., Chen, H., Fu, S. 2007. Effects of lactitol on intestinal microflora and plasma endotoxin in patients with chronic viral hepatitis. J. Infect. 54, 98–102.CrossRefGoogle Scholar
  43. Cho, Y.J., Shin, H.J., Bucke, C. 2003. Purification and biochemical properties of a galactooligosaccharide producing β-galactosidase from Bullera singularis. Biotechnol. Lett. , 25, 2107–2111.CrossRefGoogle Scholar
  44. Choi, J.J., Kwon, S.T., Oh, E.J. 2004a. Method for synthesis of galactooligosaccharide using Thermus caldophilus gk24 β-glycosidase and high-level expression system of recombinant Thermus caldophilus gk-24 β-glycosidase used in the same method – plasmid mediated gene transfer and expression in Escherichia coli for recombinant saccharide production. Korean Patent KR 2004033748, issued 28 Apr 2004.Google Scholar
  45. Choi, H-J., Kim, C.S., Kim, P., Jung, H-C., Oh, D-K. 2004b. Lactosucrose bioconversion from lactose and sucrose by whole cells of Paenibacillus polymyxa harbouring levansucrase activity. Biotechnol. Prog. 20, 1876–1879.CrossRefGoogle Scholar
  46. Chonan, O., Matsumoto, K., Watanuki, M. 1995. Effect of galacto-oligosaccharides on calcium absorption and preventing bone loss in ovariectomized rats. Biosci. Biotechnol. Biochem. 59, 236–239.CrossRefGoogle Scholar
  47. Codex Alimentarius. 1998. Food Labelling Complete Texts. FAO/WHO, Rome.Google Scholar
  48. Crittenden, R.G. 1999. Prebiotics. In: Probiotics: A Critical Review (G.W. Tannock, ed.), pp. 141– 156, Horizon Scientific Press, Wymondham, UK.Google Scholar
  49. Crittenden, R.G., Playne, M.J. 1996. Production, properties and applications of food-grade oligosaccharides. Trends Food Sci. Technol. 7, 353–361.CrossRefGoogle Scholar
  50. Crittenden, R.G., Playne, M.J. 2002. Purification of food-grade oligosaccharides using immobilised cells of Zymomonas mobilis. Appl. Microbiol. Biotechnol. 58, 297–302.CrossRefGoogle Scholar
  51. Croft-Hill, A. 1898. Reversible zymohydrolysis. J. Chem. Soc. LXIII, 634–658.Google Scholar
  52. Crout, D.H.G., Vic, G. 1998. Glycosidases and glycosyl transferases in glycoside and oligosaccharide synthesis. Curr. Opinion Chem. Biol. 2, 98–111.CrossRefGoogle Scholar
  53. Cummings, J.H., Macfarlane, G.T., Macfarlane, S. 2003. Intestinal bacteria and ulcerative colitis. Curr. Iss. Intest. Microbiol. 4, 9–20.Google Scholar
  54. Dbouk, N., McGuire, B.M. 2006. Hepatic encephalopathy: a review of its pathophysiology and treatment. Curr. Treatment Options Gastroenterol. 9, 464–474.CrossRefGoogle Scholar
  55. De Preter, V., Geboes, K., Verbrugghe, K., De Vuyst, L., Vanhoutte, T., Huys, G., Swings, J., Pot, B., Verbeke, K. 2004. The in vivo use of the stable isotope-labelled biomarkers lactose-[N-15]ureide and [H-2(4)]tyrosine to assess the effects of pro- and prebiotics on the intestinal flora of healthy human volunteers. Br. J. Nutr. 92, 439–446.CrossRefGoogle Scholar
  56. De Preter, V., Vanhoutte, T., Huys, G., Swings, J., Rutgeerts, P., Verbeke, K. 2006. Effect of lactulose and Saccharomyces boulardii administration on the colonic urea-nitrogen metabolism and the bifidobacteria concentration in healthy human subjects. Alimentary Pharmacol. Therapeutics 23, 963–974.CrossRefGoogle Scholar
  57. De Slegte, J., et al. 2002. Determination of trans-galactooligosaccharides in selected food products by ion-exchange chromatography: collaborative study. J. Ass. Off. Anal. Chem. Internat. 85, 417–423.Google Scholar
  58. Dombou, M., Tomioka, I., Tsurutani, R., Kitabatake, S., Nakajima, H. 1994. Method for production of a growth factor for Bifidobacterium sp. US Patent 5,294, 546, issued 15 March 1994, assigned to Unitika Ltd, Japan.Google Scholar
  59. Dorscheid, R.E., Krumbholz, M.J. 1991. Method of manufacturing lactulose. US Patent 5,071, 530, issued 10 Dec 1991, assigned to Duphar International Research B.V.Google Scholar
  60. Edwards, C.A., Parrett, A.M. 2002. Intestinal flora during the first months of life: new perspectives. Br. J. Nutr. 88(Suppl 1), S11–S18.CrossRefGoogle Scholar
  61. Fanaro, S., Boehm, G., Garssen, J., Knol, J., Mosca, F., Stahl, B., Vigi, V. 2005. Galacto-oligosaccharides and long-chain fructo-oligosaccharides as prebiotics in infant formulas: a review. Acta Paediatrica 94, 22–26.CrossRefGoogle Scholar
  62. Favier, C., Neut, C., Mizon, C., Cortot, A., Colombel, J.F., Mizon, J. 1997. Fecal beta-D-galactosidase production and bifidobacteria are decreased in Crohn's disease. Digestive Dis. Sci. 42, 817–822.CrossRefGoogle Scholar
  63. Ferchaud-Roucher, V., Pouteau, E., Piloquet, H., Zaïr, Y., Krempf, M. 2005. Colonic fermentation from lactulose inhibits lipolysis in overweight subjects. Am. J. Physiol. 289, E716–E720.Google Scholar
  64. Fernández-Bañares, F. 2006. Nutritional care of the patient with constipation. Clin. Gastroenterol. 20, 575–587.Google Scholar
  65. Finkelman, M.A.J. 1989. Yeast strain development for extracellular enzyme production. In: Yeast Strain Selection (C.J. Panchal, ed.), pp. 185– 223, Marcel Dekker Inc., New York.Google Scholar
  66. Fu, W., Song, K. 1993. Removal of boric acid catalyst in lactose isomerization. Chinese Patent CN 1,073,668.Google Scholar
  67. Fujimori, I. 1992. Pet food, US Patent 5,294, 458, issued Mar 15, 1994, assigned to Maruha Corporation and Ensuiko Sugar Refining Co., Ltd., Japan.Google Scholar
  68. Fujita K., Hara K., Hashimoto H., Kitahata S. 1990a. Purification and some properties of β-fructofuranosidase I from Arthrobacter sp. K-1. Agric. Biol. Chem. 54, 913–919.CrossRefGoogle Scholar
  69. Fujita, K., Hara, K., Hashimoto, H., Kitahata, S. 1990b. Transfructosylation catalyzed by β-fructofuranosidase I from Arthrobacter sp. K-1 Agric. Biol. Chem. 54, 2655–2661.CrossRefGoogle Scholar
  70. Fujita, K., Hara, K., Hashimoto, H., Kitahata, S. 1992a. Method for the preparation of fructose-containing oligosaccharide US Patent 5,089, 401, issued Feb 18, 1992, assigned to Ensuiko Sugar Refining Co Ltd., Japan.Google Scholar
  71. Fujita K, Kitahata S, Hara, K., Hashimoto, H. 1992b. Production of lactosucrose and its properties. In: Carbohydrates in Industrial Synthesis (M.A. Clarke, ed.), pp. 68– 76, Proc. Symp. Div. Carbohyd. Chem. Amer. Chem. Soc., Bartens, Berlin.Google Scholar
  72. Fujita, K., Hara, K., Sakai, S., Miyake, T., Yamashita, M., Tsunstomi, Y., Mitsuoka, Y. 1991. Effects of 4-β-D-galactosylsucrose (lactosucrose) on intestinal flora and its digestibility in humans. J. Jap. Soc. Starch Sci. 38, 249–255.CrossRefGoogle Scholar
  73. Garman, J., Coolbear, T., Smart, J.B. 1996. The effect of cations on the hydrolysis of lactose and the transferase reactions catalysed by β-galactosidase from six strains of lactic acid bacteria. Appl. Microbiol. Biotechnol. 46, 22–27.CrossRefGoogle Scholar
  74. German Culture Collection. 2007., accessed October 15, 2007.
  75. Gibson, G.R., McCartney, A.L., Rastall, R.A. 2005. Prebiotics and resistance to gastrointestinal infections. Br. J. Nutr. 93, 31–34.CrossRefGoogle Scholar
  76. Gibson, G. R., Probert, H. M., Van Loo, J.A.E., Roberfroid, M.B. 2004. Dietary modulation of the human colonic microflora: updating the concept of prebiotics. Nutr. Res. Rev. 17, 257–259.CrossRefGoogle Scholar
  77. Gibson, G.R., Roberfroid, M.B. 1995. Dietary modulation of the human colonic microbiota – introducing the concept of prebiotics. J.Nutr. 125, 1401–1412.Google Scholar
  78. Gorin, P.A., Spencer, J.F.T., Phaff, H.J. 1964. The structures of galactosyl-lactose and galactobiosyl-lactose produced from lactose by Sporobolomyces singularis. Can. J. Chem. 42, 1341–1344.CrossRefGoogle Scholar
  79. Greenberg, N.A., Mahoney, R.R. 1982. Production and characterization of β-galactosidase from Streptococcus thermophilus. J. Food Sci. 47, 1824–1828, 1835.CrossRefGoogle Scholar
  80. Greenberg, N.A., Mahoney, R.R. 1983. Formation of oligosaccharides by β-galactosidase from Streptococcus thermophilus. Food Chem. 10, 195–204.CrossRefGoogle Scholar
  81. Griffiths, M.W., Muir, D.D. 1978. Properties of a thermostable β-galactosidase from a thermophilic Bacillus: Comparison of the enzyme activity of whole cells, purified enzyme and immobilized whole cells. J. Sci. Food Agric. 29, 753–761.CrossRefGoogle Scholar
  82. Grogan, D.W. (1991). Evidence that β-galactosidase of Sulfobus solfataricus is only one of several activities of a thermostable β-D-glucosidase. Appl. Environ. Microbiol. 57, 1644–1649.Google Scholar
  83. Guarner, F., Malagelada, J.R. 2003. Gut flora in health and disease. Lancet 361, 512–519.CrossRefGoogle Scholar
  84. Guth, J.H., Tumerman, L. 1970. Method of making lactulose. US Patent 3,546,206. Dec. 8, 1970, assigned to Kraftco Corp.Google Scholar
  85. Gyorgy, P., Norris, R.F., Rose, C.S. 1954a. Bifidus factor I. A variant of Lactobacillus bifidus requiring a special growth factor. Arch. Biochem. Biophys. 48, 193–201.CrossRefGoogle Scholar
  86. Gyorgy, P., Kuhn, R., Rose, C.S., Zilliken, F. 1954b. Bifidus factor II. Its occurrence in milk from different species and in other natural products. Arch. Biochem. Biophys. 48, 202–208.CrossRefGoogle Scholar
  87. Haarman, M., Knol, J. 2005. Quantitative real-time PCR assays to identify and quantify fecal Bifidobacterium species in infants receiving a prebiotic infant formula. Appl. Environ. Microbiol. 71, 2318–2324.CrossRefGoogle Scholar
  88. Haarman, M., Knol, J. 2006. Quantitative real-time PCR analysis of fecal Lactobacillus species in infants receiving a prebiotic infant formula. Appl. Environ. Microbiol. 72, 2359–2365.CrossRefGoogle Scholar
  89. Hansen, O.C., Jorgensen, F., Stougaard, P., Bertelsen, H., Bottcher, K., Christensen, H.J.S., Eriknauer, K. 2006. Thermostable isomerase and use hereof, in particular for producing tagatose. US Patent 7,052, 898, issued 30 May 2006, assigned to Bioneer A/S.Google Scholar
  90. Hara, K., Fujita, K., Yamashita, M., Tsunetomi, Y., Sakai, S., Miyake, T. 1992. Process for preparing lactosucrose high-content powder. US Patent 5,130, 239, issued July 14, 1992, assigned to KK Hayashibara SKK, and Ensuiko SKK.Google Scholar
  91. Hara, K., Fujita, K., Yamashita, M., Tsunetomi, Y., Sakai, S., Miyake, T. 1994a. Process for preparing a powder having a high concentration of lactosucrose and use of said powder. US Patent 5,296, 473, March 22, 1994, assigned to KK Hayashibara SKK.Google Scholar
  92. Hara, H., Li, S.-T., Sasaki, M., Maruyama, T., Terada, A., Ogata, Y., Fujita, K., Ishigami, H., Hara, K., Fujimori, I., Mitsuoka, T. 1994b. Effective dose of lactosucrose on fecal flora and fecal metabolites of humans. Bifidobacteria Microfl. 13, 51–63.Google Scholar
  93. Hardy, M.R., Townsend, R.R. 1988. Separation of positional isomers of oligosaccharides and glycopeptides by high-performance anion-exchange chromatography with pulsed amperometric detection. Proc. Natl. Acad. Sci., USA 85, 3289–3293.CrossRefGoogle Scholar
  94. Harmsen, H.J.M., Wildeboer-Veloo, A.C.M., Raangs, C.G., Wagendorp, A.A., Klijn, N., Bindels, J.G., Welling, G.W. 2000. Analysis of intestinal flora development in breast-fed and formula-fed infants by using molecular identification and detection methods. J. Pediatr. Gastroenterol. Nutr. 30, 61–67.CrossRefGoogle Scholar
  95. Heavey, P.M., Savage, S.A., Parrett, A., Cecchini, C., Edwards, C.A., Rowland, I.R. 2003. Protein-degradation products and bacterial enzyme activities in faeces of breast-fed and formula-fed infants. Br. J. Nutr. 89, 509–515.CrossRefGoogle Scholar
  96. Hicks, K.B. 1981. Ketose sugars from aldose sugars. U.S. Pat. No. 4,273, 922, issued Jun. 16, 1981, assigned to USA.Google Scholar
  97. Hicks, K.B., Parrish, F.W. 1980. A new method for the preparation of lactulose from lactose. Carbohydr. Res. 82, 393–397.CrossRefGoogle Scholar
  98. Hicks, K.B., Simpson, G.L., Bradbury, A.G.W. 1986. Removal of boric acid and related compounds from solutions of carbohydrates with boron-selective resin (IRA-743). Carbohydr. Res. 147, 39–48.CrossRefGoogle Scholar
  99. Holma, R., Juvonen, P., Asmawi, M.Z., Vapaatalo, H., Korpela, R. 2002. Galacto-oligosaccharides stimulate the growth of bifidobacteria but fail to attenuate inflammation in experimental colitis in rats. Scand. J. Gastroenterol. 37, 1042–1047.CrossRefGoogle Scholar
  100. Inchem. 2008. International Programme on Chemical Safety (IPCS) and the Canadian Centre for Occupational Health and Safety (CCOHS) website IPCS INCHEM. accessed 17 April 2008.
  101. IFST. 2007. Information Statement on Dietary Fibre. (Institute of Food Science & Technology Trust Fund, London, U.K.) 10 pages., accessed 5 June 2007.
  102. IDF. 1995. Provisional Standard. Milk. Determination of lactulose content. Enzymatic method. International Dairy Federation, Brussels, Standard 175.Google Scholar
  103. Ipatiew, W. 1912. Katalytische Reaktionen bei hohen Temperaturen und Drucken. XXV Berichte der Deutschen Chemischen Gesselschaft. 45, 3218–3226 [in German].CrossRefGoogle Scholar
  104. Ishikawa, E., Sakai, T., Ikemura, H., Matsumoto, K., Abe, H. 2005. Identification, cloning, and characterization of a Sporobolomyces singularis β-galactosidase-like enzyme involved in galacto-oligosaccharide production. J. Biosci.Bioeng. 99, 331–339.CrossRefGoogle Scholar
  105. IUPAC. 1996. Nomenclature of carbohydrates. Pure Appl. Chem. 68, 1919–2008.CrossRefGoogle Scholar
  106. Izume, M., Nagae, S., Kawagishi, H., Ohtakara, A. 1992. Preparation of N-acetylchitooligosaccharides from enzymatic hydrolyzates of chitosan. Biosci. Biotech. Biochem. 56, 1327–1328.CrossRefGoogle Scholar
  107. JECFA. 2008. Joint FAO/WHO Expert Committee on Food Additives., accessed 17 April 2008.
  108. Ji, E.S., Park, N.H., Oh, D.K. 2005. Galacto-oligosaccharide production by a thermostable recombinant β-galactosidase from Thermotoga maritima – Thermotaga maritima recombinant thermostable β-galactosidase production for galacto-oligosaccharide preparation. World J. Microbiol. Biotechnol. 21, 759–764.CrossRefGoogle Scholar
  109. Johansson, E., Hedbys, L., Mosbach, K., Larsson, P.-O. 1989. Studies of the reversed-mannosidase reaction in high concentrations of mannose. Enz. Microbial. Technol. 11, 347–352.CrossRefGoogle Scholar
  110. Jorgensen, F., Hansen, O.C., Stougaard, P. 2001. High efficiency synthesis of oligosaccharides with a truncated β-galactosidase from Bifidobacterium bifidum. Appl. Microbiol. Biotechnol. 57, 647–652.CrossRefGoogle Scholar
  111. Jouët, P., Sabate, J.-M., Cuillerier, E., Coffin, B., Lemann, M., Jian, R., Flourie, B. 2006. Low-dose lactulose produces a tonic contraction in the human colon. Neurogastroenterol. Motility 18, 45–52.CrossRefGoogle Scholar
  112. Juśkiewicz, J., Klewicki, R., Zdunczyk, Z. 2006. Consumption of galactosyl derivatives of polyols beneficially affects cecal fermentation and serum parameters in rats. Nutr. Res. 26, 531–536.CrossRefGoogle Scholar
  113. Kawakami, K., Makino, I., Asahara, T., Kato, I., Onoue, M. 2005. Dietary galacto-oligosaccharides mixture can suppress serum phenol and p-cresol levels in rats fed tyrosine diet. J. Nutr. Sci. Vitaminol. 51, 182–186.CrossRefGoogle Scholar
  114. Kawase, M., Pilgrim, A., Araki, T., Hashimoto, K. 2001. Lactosucrose production using a simulated moving bed reactor. Chem. Eng. Sci. 56, 453–458.CrossRefGoogle Scholar
  115. Kim, P. 2004. Current studies on biological tagatose production using L-arabinose isomerase: A review and future prospects. Appl. Microbiol. Biotechnol. 65, 243–249.Google Scholar
  116. Kirjavainen, P.V., Reid, G. 2006. The infant intestinal microbiota in allergy. In: Gastrointestinal Microbiology (A.C. Ouwehand, E. E. Vaughan, eds.), pp. 189– 205, Taylor and Francis, New York.Google Scholar
  117. Knol, J., Boehm, G., Lidestri, M., Negretti, F., Jelinek, J., Agosti, M., Stahl, B., Marini, A., Mosca, F. 2005. Increase of faecal bifidobacteria due to dietary oligosaccharides induces a reduction of clinically relevant pathogen germs in the faeces of formula-fed preterm infants. Acta Paed. 94, 31–33.CrossRefGoogle Scholar
  118. Kobata, A. 1996. Glycobiology. In: Encyclopaedia of Molecular Biology and Molecular Medicine (R.A. Meyers, ed.), Volume 2, pp. 446– 457, VCH, Weinheim, Germany.Google Scholar
  119. Kobayashi, Y., Kan, T., Terashima, T. 1990. Method for producing processed milk containing galactooligosaccharide. U.S. Patent 4944952. issued 31 July 1990; assigned to K.K. Yakult Honsha.Google Scholar
  120. Koizumi, S., Endo, T., Tabata, K., Ozaki, A. 1998. Large-scale production of UDP-galactose and globotiose by coupling metabolically engineered bacteria. Nature Biotechnol. 16, 847–850.CrossRefGoogle Scholar
  121. Kozempel, M.F., Kurantz, M.J. 1994. The isomerization kinetics of lactose to lactulose in the presence of borate. J. Chem. Tech. Biotechnol. 59, 25–29.CrossRefGoogle Scholar
  122. Kummel, K.F., Brokx, S. 2001. Lactitol as a functional prebiotic. Cereal Foods World 46, 424–429.Google Scholar
  123. Kunz, C., Rudloff, S. 1996. Strukturelle und funktionelle aspekte von oligosacchariden in frauenmilch. Z. Ernahrungswiss. 35, 22–31.CrossRefGoogle Scholar
  124. Kunz, C., Rudloff, S. 2002. Health Benefits of Milk-Derived Carbohydrates. Bulletin 375, International Dairy Federation, Brussels, pp. 72–79.Google Scholar
  125. Kunz, C., Rudloff, S., Baier, W., Klein, N., Strobel, S. 2000. Oligosaccharides in human milk: structural, functional, and metabolic aspects. Ann. Rev. Nutr. 20, 699–722.CrossRefGoogle Scholar
  126. Laerke, H.N., Jensen, B.B. 1999. D-Tagatose has low small intestinal digestibility but high large intestinal fermentability in pigs. J. Nutr. 129, 1002–1009.Google Scholar
  127. Laerke, H.N., Jensen, B.B., Hojsgaard, S. 2000. In vitro fermentation pattern of D-tagatose is affected by adaptation of the microbiota from the gastrointestinal tract of pigs. J. Nutr. 130, 1772–1779.Google Scholar
  128. LFRA. 2000. Ingredients Handbook: Prebiotics and probiotics (G. Gibson, F. Angus, eds.), Leatherhead Food Research Association Ltd., Surrey, UK.Google Scholar
  129. Lee, Y.C. (1990). High performance anion-exchange chromatography for carbohydrate analysis. Anal. Biochem. 189, 151–162.CrossRefGoogle Scholar
  130. Lee, Y-J., Kim, C.S., Oh, D-K. 2004. Lactulose production by β-galactosidase in permeabilized cells of Kluyveromyces lactis. Appl. Microbiol. Biotechnol. 64, 787–793.CrossRefGoogle Scholar
  131. Lemoine, J., Chirat, F., Wieruszeski, J.-M, Strecker, G., Favre, N., Neeser, J.-R. 1997. Structural characterization of the exocellular polysaccharides produced by Streptococcus thermophilus SFi39 and SFi12. Appl. Environ. Microbiol., 63, 3512–3518.Google Scholar
  132. Linko, S., Enwald, S., Vahvaselka, M., Mayra-Makinen, A. 1992. Optimization of the production of β-galactosidase by an autolytic strain of Streptococcus salivarius subsp. thermophilus. Ann. New York Acad. Sci. 672, 588–594.CrossRefGoogle Scholar
  133. Linskens, R.K., Huijsdens, X.W., Savelkoul, P.H.M., Vandenbroucke-Grauls, C.M.J.E., Meuwissen, S.M.G. 2001. The bacterial flora in inflammatory bowel disease: Current insights in pathogenesis and the influence of antibiotics and probiotics. Scand. J. Gastroenterol. 36, S29–S40.CrossRefGoogle Scholar
  134. Ludwig, R., Ozga, M., Zamocky, M., Peterbauer, C., Kulbe, K.D., Haltrich, D. 2004. Continuous enzymatic regeneration of electron acceptors used by flavoenzymes: Cellobiose dehydrogenase-catalyzed production of lactobionic acid as an example. Biocatal. Biotransform. 22, 97–104.CrossRefGoogle Scholar
  135. Macfarlane, S., Macfarlane, G.T., Cummings, J.H. 2006. Review article: prebiotics in the gastrointestinal tract. Aliment. Pharmacol. Therapeut. 24, 701–714.CrossRefGoogle Scholar
  136. Mahoney, R.R. 1997. Lactose: enzymatic modification. In: Advanced Dairy Chemistry (P.F. Fox, ed.), 2nd Edition, Vol. 3, pp. 77–125, Chapman & Hall, London.Google Scholar
  137. Mahoney, R.R., Whitaker, J.R. 1978. Purification and physico-chemical properties of β-galactosidase from Kluyveromyces fragilis. J. Food Sci. 43, 584–591.CrossRefGoogle Scholar
  138. Mahoney, R.R., Nickerson, T.A., Whitaker, J.R. 1975. Selection of strain, growth conditions, and extraction procedures for optimum production of lactase from Kluyveromyces fragilis. J. Dairy Sci. 58, 1620–1629.CrossRefGoogle Scholar
  139. Marteau, P., Seksik, P., Shanahan, F. 2003. Manipulation of the bacterial flora in inflammatory bowel disease. Best Practice Res: Clin. Gastroenterol. 17, 47–61.CrossRefGoogle Scholar
  140. Matsumoto, K., Kobayashi, Y., Ueyama, S., Watanabe, T., Tanaka, R., Kan, T., Kuroda, A., Sumihara, Y. 1993. Galactooligosaccharides. In: Oligosaccharides. Production, Properties, and Applications (T. Nakakuki, ed.), Japanese Technology Reviews Vol 3, No. 2, pp. 90–106, Gordon and Breach, Science Publishers, Basel.Google Scholar
  141. McCartney A.L., Gibson, G.R. 2006. The normal microbiota of the human gastrointestinal tract: history of analysis, succession, and dietary influences. In: Gastrointestinal Microbiology (A.C. Ouwehand, E.E. Vaughan, eds.), pp. 51–73, Taylor and Francis, New York.Google Scholar
  142. Mendicino, J. F. (1960). Effect of borate on the alkali-catalyzed isomerisation of sugars. J. Am. Chem. Soc., 82, 4975–4979.CrossRefGoogle Scholar
  143. Mesters, P.H.J., Brokx, S. 2000. Lactitol: a functional prebiotic. Functional Foods 2000 Conference Proceedings, The Hague, The Netherlands (F. Angus, C. Miller, eds.), pp. 173–189, Leatherhead Publishing, UK.Google Scholar
  144. Meyer, D., Tungland, B. 2001. Non-digestible oligosaccharides: their physiological effects and health implications. In: Advanced Dietary Fibre Technology (B.V. McCleary, L. Prosky, eds.), pp. 455– 470, Blackwell Publishing, Oxford, UK.Google Scholar
  145. Minami,Y., Yazawa, K., Tamura, Z., Tanaka, T., Yamamoto, T. 1983. Selectivity of utilization of galactosyl-oligosaccharides by bifidobacteria. Chem. Pharm. Bull. 31, 1688–1691.CrossRefGoogle Scholar
  146. Miyamoto, Y., Ooi, T., Kinoshita, S. 2000. Production of lactobionic acid from whey by Pseudomonas sp. LS13-1. Biotechnol. Lett. 22, 427–430.CrossRefGoogle Scholar
  147. Mizota, T., Tamura, Y., Tomita, M., Okonogi, S. 1987. Lactulose as a Sugar with Physiological Significance. Bulletin 212, International Dairy Federation, Brussels, pp. 69–76.Google Scholar
  148. Mizota, T. 1996. Lactulose as a growth promoting factor for Bifidobacterium and its physiological aspects. Bulletin 313, International Dairy Federation, Brussels, pp. 43–48.Google Scholar
  149. Modler, H.W., McKellar, R.C., Yaguchi, M. 1990. Bifidobacteria and bifidogenic factors. Can. Inst. Food Sci. Technol. 23, 29–41.Google Scholar
  150. Montgomery, E.M., Hudson, C.S. 1930. Relations between rotatory power and structure in the sugar group. XXVII. Synthesis of a new disaccharide ketose (lactulose) from lactose. J. Am. Chem. Soc. 52, 2101–2106.CrossRefGoogle Scholar
  151. Morohashi, T. 2002. The effect on bone of stimulated intestinal mineral absorption following fructooligosaccharide consumption in rats. Biosci. Microfl. 21, 21–25.Google Scholar
  152. Mountzouris, K.C., McCartney, A.L., Gibson, G.R. 2002. Intestinal microflora of human infants and current trends for its nutritional modulation. Br. J. Nutr. 87, 405–420.Google Scholar
  153. Mozaffar, Z., Nakanishi, K., Matsuno, R., Kamikubo, T. 1984. Purification and properties of β-galactosidase from Bacillus circulans. Agric. Biol. Chem. 48, 3053–3061.CrossRefGoogle Scholar
  154. Mwenya, B., Santoso, B., Sar, C., Gamo, Y., Kobayashi, T., Arai, I., Takahashi, J. 2004a. Effects of including β1-4 galacto-oligosaccharides, lactic acid bacteria or yeast culture on methanogenesis as well as energy and nitrogen metabolism in sheep. Anim. Feed Sci. Technol. 115, 313–326.CrossRefGoogle Scholar
  155. Mwenya, B., Zhou, X., Santoso, B., Sar, C., Gamo, Y., Kobayashi, T., Takahashi, J. 2004b. Effects of probiotic-vitacogen and β1-4 galacto-oligosaccharides supplementation on methanogenesis and energy and nitrogen utilization in dairy cows. Asian-Austral. J. Anim. Sci. 17, 349–354.Google Scholar
  156. Nagendra, R., Rao, S.V. 1992. An improved colorimetric method for the estimation of lactulose in lactose-lactulose mixtures. Food. Chem. 43, 399–402.CrossRefGoogle Scholar
  157. Nakakuki, T. 2002. Present status and future of functional oligosaccharide development in Japan. Pure Appl. Chem. 74, 1245–1251.CrossRefGoogle Scholar
  158. Nakanishi, K., Matsuno, R., Torii, K., Yamamoto, K., Kamikubo, T. 1983. Properties of immobilized β-galactosidase from Bacillus circulans. Enz. Microb. Technol. 5, 115–120.CrossRefGoogle Scholar
  159. Nakao, M., Harada, M., Kodama, Y., Nakayama, T., Shibano, Y., Amachi, T. 1994. Purification and characterization of a thermostable β-galactosidase with high transgalactosylation activity from Saccharopolyspora rectivirgula. Appl. Microb. Biotechnol. 40, 657–663.CrossRefGoogle Scholar
  160. Nakayama, T., Kodama, Y., Amano, N., Nakao, M., Shibano, Y., Amachi, T. 1992. Heat-resistant β-galactosyltransferase, its production process and its use. United States Patent 5153128. issued 10 June 1992; assigned to Suntory ltd., Osaka, Japan.Google Scholar
  161. Nakayama, T., Kodama, Y., Amano, N., Nakao, M., Shibano, Y., Amachi, T. 1993. Process for producing novel heat-resistant β-galactosyltransferase. U.S.Patent 5,234,828, issued 10 Aug 1993; assigned to Suntory Ltd, Osaka, Japan.Google Scholar
  162. NCBI. 2007. National Center for Biological Information, US National Library of Medicine, USA, Taxonomy browser (, accessed 13 August 2007.
  163. Nilsson, K.G.I. 1988. Enzymatic synthesis of oligosaccharides. Trends Biotechnol. 6, 256–264.CrossRefGoogle Scholar
  164. Normen, L., Laerke, H. N., Jensen, B.B., Langkilde, A.M., Andersson, H. 2001. Small-bowel absorption of D-tagatose and related effects on carbohydrate digestibility: an ileostomy study. Am. J. Clin. Nutr. 73, 105–110.Google Scholar
  165. Ohkusa, T., Ozaki,Y., Sato, C., Mikuni, K., Ikeda, H. 1995. Long-term ingestion of lactosucrose increases Bifidobacterium sp. in human fecal flora. Digestion 56, 415–420.CrossRefGoogle Scholar
  166. Ohtsuka, K., Oki, S., Owaza, O., Uchida, T. 1992. [Isolation and cultural conditions of galactooligosaccharide producing yeast Cryptococcus laurentii]. Hakkokogaku Kaishi 66, 225–233.Google Scholar
  167. Ohtsuka, K., Tanoh, A., Ozawa, O., Kanematsu, T., Uchida, T., Shinke, R. 1990. Purification and properties of a β-galactosidase with high galactosyl transfer activity from Cryptococcus laurentii. J. Ferment. Bioeng. 70, 301–307.CrossRefGoogle Scholar
  168. Onishi, N., Kira, I., Yokozeki, K. 1996. Galacto-oligosaccharide production from lactose by Sirobasidium magnum CBS6803. Lett. Appl. Microbiol. 23, 253–256.CrossRefGoogle Scholar
  169. Onishi, N., Tanaka, T. 1995. Purification and properties of a novel thermostable galacto-oligosaccharide-producing β-galactosidase from Sterigmatomyces elviae CBS 8119. Appl. Environ. Microbiol. 61, 4026–4030.Google Scholar
  170. Onishi, N., Tanaka, T. 1996. Purification and properties of a galacto- and gluco-oligosaccharide-producing β-glycosidase from Rhodotorula minuta IFO879. J. Ferment. Bioeng. 82, 439–443.CrossRefGoogle Scholar
  171. Onishi, N., Tanaka, T. 1997. Purification and characterization of galacto-oligosaccharide producing β-galactosidase from Sirobasidium magnum. Lett. Appl. Microbiol. 24, 82–86.CrossRefGoogle Scholar
  172. Onishi, N., Yamashiro, A., Yokozeki, K. 1995. Production of galacto-oligosaccharide from lactose by Sterigmatomyces elviae CBS 8119. Appl. Environ. Microbiol. 61, 4022–4025.Google Scholar
  173. Onishi, N., Yokozeki, K. 1992. Method for producing galactose transfer products. US Patent 5149640; issued Sept 22, 1992, assigned to Ajinomoto Co., Inc.Google Scholar
  174. Özaslan, C., Türkçapar, A.G., Kesenci, M., Karayalçin, K., Yerdel, M.A., Bengisun, S., Törüner, A. 1997. Effect of lactulose on bacterial translocation. Eur. J. Surg. 163, 463–467.Google Scholar
  175. Ozawa,O., Ohtsuka, K., Uchida, T., Usami, S. 1991. 4′-Galactosyl lactose production in a jar fermentor by Cryptococcus laurentii OKN-4. J. Ferm. Bioeng. 72, 309–310.CrossRefGoogle Scholar
  176. Park, N.-H., Choi, H.-J., Oh, D.-K. 2005. Lactosucrose production by various microorganisms harbouring levansucrase activity. Biotechnol. Lett. 27, 495–497.CrossRefGoogle Scholar
  177. Parrish, F.W. 1970. Isomerization of glucose, maltose and lactose with amino compounds. US Patent 3,514,327. May 26, 1970, assigned to US Army.Google Scholar
  178. Pazur, J.H. 1970. Oligosaccharides. In: The Carbohydrates: Chemistry and Biochemistry (W. Pigman, D. Horton, A. Herp, eds.), pp. 69–137, Vol. IIA, 2nd edition, Academic Press, New York.Google Scholar
  179. Pazur, J.H. 1953. The enzymatic conversion of lactose into galactosyl oligosaccharides. Science 117, 355–356.CrossRefGoogle Scholar
  180. Pazur, J.H. 1954. The mechanism of enzymatic synthesis of galactosyl oligosaccharides. J. Biol. Chem. 208, 439–444.Google Scholar
  181. Pazur, J.H., Tipton, C.L., Budovich, T., Marsh, J.M. 1958. Structural characterization of products of enzymatic disproportionation of lactose. J. Am. Chem. Soc. 80, 119–121.CrossRefGoogle Scholar
  182. Petuely, F. 1957. Bifidusflora bei flaschenkindern durch bifidogene substanzen (Bifidusfaktor). Z. Kinderheilkunde 79, 174–179.CrossRefGoogle Scholar
  183. Petzelbauer, I., Nidetzky, B., Haltrich, D., Kulbe, K.D. 1999. Development of an ultra high temperature process for the enzymatic hydrolysis of lactose. I. The properties of two thermostable β-glycosidases. Biotechnol. Bioeng. 64, 322–332.CrossRefGoogle Scholar
  184. Petzelbauer I., Zeleny, R., Reiter, A., Kulbe, K.D., Nidetzky, B. 2000. Development of an ultra high temperature process for the enzymatic hydrolysis of lactose. II. Oligosaccharide formation by two thermostable β-glycosidases. Biotechnol. Bioeng. 69, 140–149.CrossRefGoogle Scholar
  185. Petzelbauer, I., Splechtna, B., Nidetzky, B. 2002a. Development of an ultra high temperature process for the enzymatic hydrolysis of lactose. III. Utilization of two thermostable β-glycosidases in a continuous ultrafiltration membrane reactor and galacto-oligosaccharide formation under steady-state conditions. Biotechnol. Bioeng. 77, 394–404.CrossRefGoogle Scholar
  186. Petzelbauer, I., Kuhn, B., Splechtna, B., Kulbe, K.D., Nidetzky, B. 2002b. Development of an ultra high temperature process for the enzymatic hydrolysis of lactose. IV. Immobilization of two thermostable β-glycosidases and optimization of a packed-bed reactor for lactose conversion. Biotechnol. Bioeng. 77, 619–631.CrossRefGoogle Scholar
  187. Pilgrim, A., Kawase, M., Ohashi, M., Fujita, K., Murakami, K., Hashimoto, K. 2001. Reaction kinetics and modeling of the enzyme-catalyzed production of lactosucrose using β-fructofuranosidase from Arthrobacter sp. K-1. Biosci. Biotechnol. Biochem. 65, 758–765.CrossRefGoogle Scholar
  188. Pisani, F. M., Rella, R., Raia, C., Rozzo, C., Nucci, R., Gambacotra, A., DeRosa, M., Rossi, M. 1990. Thermostable β-galactosidase from the archaebacterium Sulfolobus solfataricus: purification and properties. Eur. J. Biochem. 187, 321–328.CrossRefGoogle Scholar
  189. Playne, M.J., Morel, B., Dimopoulos, A. 1993. Production of carbohydrate-based functional foods using enzyme and fermentation technologies. Proc. 11th Australian Biotechnol. Conf., Perth, pp. 207–209.Google Scholar
  190. Playne, M.J., Crittenden, R. 1996. Commercially-available Oligosaccharides. Bulletin 313, International Dairy Federation, Brussels. pp.10–22.Google Scholar
  191. Playne, M.J. 2002a. Galacto-oligosaccharides. In: Encyclopaedia of Dairy Sciences (H. Roginski, J.W. Fuquay, P.F. Fox eds.), pp. 1151–1158, Academic Press, San Diego, CA, USA.Google Scholar
  192. Playne, M.J. 2002b. Glycoscience: oligosaccharides as drugs, functional foods, and receptors in the gut. Australas. Biotechnol. 12, 35–37.Google Scholar
  193. Ponz de Leon, M., Roncucci, L. 1997. Chemoprevention of colorectal tumours: role of lactulose and of other agents. Scand. J. Gastroenterol. 32 Suppl. 222, 72–75.Google Scholar
  194. Prasad, S., Dhiman, R.K., Duseja, A., Chawla, Y.K., Sharma, A., Agarwal, R. 2007. Lactulose improves cognitive functions and health-related quality of life in patients with cirrhosis who have minimal hepatic encephalopathy. Hepatology 45, 549–559.CrossRefGoogle Scholar
  195. Prenosil, J.E., Stucker, E., Bourne, J.R. 1987a. Formation of oligosaccharides during enzymatic lactose: Part 1: State of art. Biotechnol. Bioeng. 30,1019–1025.CrossRefGoogle Scholar
  196. Prenosil, J.E., Stucker, E., Bourne, J.R. 1987b. Formation of oligosaccharides during enzymatic lactose hydrolysis and their importance in a whey hydrolysis process: Part II: Experimental. Biotechnol. Bioeng. 30, 1026–1031.CrossRefGoogle Scholar
  197. Pyun, Y.R., Kim, B.C., Lee, H.S., Lee, D.W., Lee, Y.H. 2005. Thermostable L-arabinose isomerase and process for preparing D-tagatose. US Patent 6,933,138 issued 23 Aug. 2005; assigned to CJ Corp.Google Scholar
  198. Quah, H.M., Ooi, B.S., Seow-Choen, F., Sng, K.K., Ho, K.S. 2006. Prospective randomized crossover trial comparing fibre with lactulose in the treatment of idiopathic chronic constipation. Tech. Coloproctol. 10, 111–114.CrossRefGoogle Scholar
  199. Queen Mary University of London 2008., accessed 15 April 2008.
  200. Quemener, B., Thibault, J.C., Coussement, P. 1994. Determination of inulin and oligofructose in food-products, and integration in the AOAC method for measurement of total dietary fiber. Lebensm. Wiss. Technol. 27, 125–132.CrossRefGoogle Scholar
  201. Rabiu, B.A., Jay, A.J., Gibson, G.R., Rastall, R.A. 2001. Synthesis and fermentation properties of novel galacto-oligosaccharides by β-galactosidases from Bifidobacterium species. Appl. Environ. Microbiol. 67, 2526–2530.CrossRefGoogle Scholar
  202. Rao, A.V. 1999. Dose-response effects of inulin and oligofructose on intestinal bifidogenesis effects. J. Nutr. 129 Suppl 7, 1442–1445.Google Scholar
  203. Rastall, R.A. 2006. Galacto-oligosaccharides as prebiotics. In: Prebiotics: Development and Application (G.R. Gibson, R.A. Rastall, eds.), pp. 101– 110, John Wiley & Sons, Ltd, Chichester, England.Google Scholar
  204. Rastall, R.A., Bucke, C. 1992. Enzymatic synthesis of oligosaccharides. Biotechnol. Gen. Eng. Rev. 10, 253–281.Google Scholar
  205. Reddy, G.P., Bush, C.A. 1991. High-performance anion exchange-chromatography of neutral milk oligosaccharides and oligosaccharide alditols derived from mucin glycoproteins. Anal. Biochem. 198, 278–284.CrossRefGoogle Scholar
  206. Rinne, M.M., Gueimonde, M., Kalliomäki, M., Hoppu, U., Salminen, S.J., Isolauri, E. 2005. Similar bifidogenic effects of prebiotic-supplemented partially hydrolyzed infant formula and breastfeeding on infant gut microbiota. FEMS Immunol. Med. Microbiol. 43, 59–65.CrossRefGoogle Scholar
  207. Roberfroid, M. 2007. Prebiotics: the concept revisited. J. Nutr. 137 Suppl. 2, 830S–837S.Google Scholar
  208. Roberts, H.R., Pettinati, J.D. 1957. Oligosaccharide production, concentration effects in the enzymatic conversion of lactose to oligosaccharides. J. Agric. Food Chem. 5, 130–134.CrossRefGoogle Scholar
  209. Rodriguez, A.P., Leiro, R.F., Trillo, C., Cerdan, E., Siso, I.G., Becerra, M. 2006. Secretion and properties of a hybrid Kluyveromyces lactis – Aspergillus niger β-galactosidase. Microbial Cell Factories 5, 41 (accessed at
  210. Rowland, I.R., Bearne, C.A., Fischer, R., Pool-Zobel, B.L. 1996. The effect of lactulose on DNA damage induced by DMH in the colon of human flora-associated rats. Nutr. Cancer 26, 37–47.CrossRefGoogle Scholar
  211. Rowland, I.R., Tanaka. R. 1993. The effects of transgalactosylated oligosaccharides on gut flora metabolism in rats associated with a human faecal microflora. J. Appl. Bacteriol. 74, 667–674.CrossRefGoogle Scholar
  212. Ruffing, A., Chen, R.R. 2006. Metabolic engineering of microbes for oligosaccharide and polysaccharide synthesis. Microbial Cell Factories 5, 25 (accessed at
  213. Rumi, G., Tsubouchi, R., Okayama, M., Kato, S., Mózsik, G., Takeuchi, K. 2004. Protective effect of lactulose on dextran sulfate sodium-induced colonic inflammation in rats. Digest. Dis. Sci. 49, 1466–1472.CrossRefGoogle Scholar
  214. Saijonmaa, T., Heikonen, M., Kreula, M., Linko, P. 1978. Preparation and characterization of milk sugar alcohol, lactitol. Milchwissenschaft 33, 733–735.Google Scholar
  215. Saito, T., Kato, S., Maeda, T., Suzuki, S., Iijima, S., Kobayashi, T. 1992. Overproduction of thermostable β-galactosidase in Escherichia coli, its purification and molecular structure. J. Ferment. Bioeng. 74, 12–16.CrossRefGoogle Scholar
  216. Sakai, K., Katsumi, R., Ohi, H., Usui, T., Ishido, Y. 1992. Enzymatic syntheses of N-acetyllactosamine and N-acetylallolactosamine by the use of β-D-galactosidases. J. Carbohydr. Chem., 11, 553–565.Google Scholar
  217. Sako, T., Matsumoto, K., Tanaka, R. 1999. Recent progress on research and applications of non-digestible galacto-oligosaccharides. Int. Dairy J. 9, 69–80.CrossRefGoogle Scholar
  218. Santoso, B., Mwenya, B., Sar, C., Gamo, Y., Kobayashi, T., Morikawa, R., Kimura, K., Mizukoshi, H., Takahashi, J. 2004. Effects of supplementing galacto-oligosaccharides, Yucca schidigera or nisin on rumen methanogenesis, nitrogen and energy metabolism in sheep. Livestock Production Sci. 91, 209–217.CrossRefGoogle Scholar
  219. Sar, C., Santoso, B., Gamo, Y., Kobayashi, T., Shiozaki, S., Kimura, K., Mizukoshi, H., Arai, I., Takahashi, J. 2004. Effects of combination of nitrate with β1-4 galacto-oligosaccharides and yeast (Candida kefyr) on methane emission from sheep. Asian-Australasian J. Animal Sci. 17, 73–79.Google Scholar
  220. Satory, M., Furlinger, M., Haltrich, D., Kulbe, K.D., Pittner, F., Nidetzky, B. 1997. Continuous enzymatic production of lactobionic acid using glucose-fructose oxidoreductase in an ultrafiltration membrane reactor. Biotechnol. Lett. 19, 1205–1208.CrossRefGoogle Scholar
  221. Saunier, K., Doré, J. 2002. Gastrointestinal tract and the elderly: functional foods, gut microflora and healthy ageing. Dig. Liver Dis. 34, suppl S 19–S24.CrossRefGoogle Scholar
  222. Scholnick, F., Ben-Et, G., Sucharski, M.K. Maurer, E.W., Linfield, W.M. 1975. Lactose-derived surfactants: II. Fatty esters of lactitol. J. Am. Oil Chem. Soc. 52, 256–258.CrossRefGoogle Scholar
  223. Schoterman, H.C. 2001. Galactooligosaccharides: properties and health aspects. In: Advanced Dietary Fibre Technology (D.B.V. McCleary, L. Prosky, eds.), pp. 494– 502, Blackwell Publishing, UK.Google Scholar
  224. Schultz, M., Timmer, A., Herfarth, H.H., Sartor, R.B., Vanderhoof, J.A., Rath, H.C. 2004. Lactobacillus GG in inducing and maintaining remission of Crohn's disease. BMC Gastroenterol. 4, 5 (15 March 2004).CrossRefGoogle Scholar
  225. Schumann, C. 2002. Medical, nutritional and technological properties of lactulose. An update. Eur. J. Nutr. 41 Suppl 1, 17–25.Google Scholar
  226. Senderens, J.B. 1920. Hydrogenation catalytique du lactose Compt. Rend. 170, 47–50 [in French].Google Scholar
  227. She, Q., et al. 2001. The complete genome of the crenarchaeon Sulfolobus solfataricus P2. Proc. Natl. Acad. Sci. USA 98, 7835–7840.CrossRefGoogle Scholar
  228. Shimomura, Y., Maeda, K., Nagasaki, M., Matsuo, Y., Murakami, T., Bajotto, G., Sato, J., Seino, T., Kamiwaki, T., Suzuki, M. 2005. Attenuated response of the serum triglyceride concentration to ingestion of a chocolate containing polydextrose and lactitol in place of sugar. Biosci. Biotechnol. Biochem. 69, 1819–1823.CrossRefGoogle Scholar
  229. Shin, H.J., Park, J.M., Yang, J.W. 1995. Optimum culture condition of Bullera singularis for galactooligosaccharide production. Kor. J. Appl. Microbiol. Biotechnol. 23, 593–598.Google Scholar
  230. Shin, H.J., Park, J.M., Yang, J.W. 1998. Continuous production of galacto-oligosaccharides from lactose by Bullera singularis β-galactosidase immobilized in chitosan beads. Process Biochem. 33, 787–792.CrossRefGoogle Scholar
  231. Shoaf, K., Mulvey, G.L., Armstrong, G.D., Hutkins, R.W. 2006. Prebiotic galactooligosaccharides reduce adherence of enteropathogenic Escherichia coli to tissue culture cells. Infect. Immun. 74, 6920–6928.CrossRefGoogle Scholar
  232. Sienkiewicz, T., Riedel, C.-L. 1990. Whey and Whey Utilization, 2nd edn. Verlag Th. Mann, Gelsenkirchen-Buer, Germany.Google Scholar
  233. Sigma-Aldrich. 2007. Biofiles Vol. 2, No. 1, pp. 4–5.Google Scholar
  234. Smart, J.B. 1989. Physiologically interesting side reactions of β-galactosidase. Proc. 8th Australian Biotechnol. Conf., Sydney, pp. 337–340.Google Scholar
  235. Smart, J.B. 1991. Transferase reactions of the β-galactosidase from Streptococcus thermophilus. Appl. Microbiol. Technol. 34, 495–501.CrossRefGoogle Scholar
  236. Smart, J.B. 1993. Transferase Reactions of β-galactosidases – New Product Opportunities. Bulletin 289, International Dairy Federation, Brussels, pp. 16–22.Google Scholar
  237. Southgate, D.A.T., Hudson, G.J., Englyst, H. 1978. The analysis of dietary fibre- the choices for the analyst. J. Sci. Food Agric. 29, 979–988.CrossRefGoogle Scholar
  238. Swanson, K.S., Fahey Jr, G.C. 2006. Prebiotic impacts on companion animals. In: Prebiotics: Development and Application (G.R. Gibson, R.A. Rastall, eds.), pp. 213– 236, John Wiley & Sons, Ltd, Chichester, England.Google Scholar
  239. Takaichi, A., Okamoto, T., Azuma, Y., Watanabe, Y., Matsumoto, T., Miyata, K.,Sakamoto, S., Okamatsu, H. et al. 1995. Food composition for inhibiting the formation of an intestinal putrefactive product. US Patent 5,455,235., Oct 3, 1995, assigned to Otsuka Pharmaceutical Co., Ltd.Google Scholar
  240. Tamura, Y., Mizota, T., Shimamura, S., Tomita, M. 1993. Lactulose and its Application to the Food and Pharmaceutical Industries. Bulletin 289, International Dairy Federation, Brussels. pp. 43–53.Google Scholar
  241. Tamura, Z. 1983. Nutriology of bifidobacteria. Bifidobacteria Microflora 2, 3–16.Google Scholar
  242. Tanaka, R., Matsumoto, K. 1998. Recent Progress on Prebiotics in Japan, Including Galacto-oligosaccharides. Bulletin 336, International Dairy Federation, Brussels, pp. 21–27.Google Scholar
  243. Tannock, G.W., Munro, K., Bibiloni, R., Simon, M.A., Hargreaves, P., Gopal, P., Harmsen, H., Welling, G. 2004. Impact of consumption of oligosaccharide-containing biscuits on the fecal microbiota of humans. Appl. Environ. Microbiol. 70, 2129–2136.CrossRefGoogle Scholar
  244. Terada, A., Hara, H., Katoaka, M., Mitsuoka, T. 1992. Effect of lactulose on the composition and metabolic activity of human faecal flora. Microbial Ecol. Health Dis. 5, 43–50.CrossRefGoogle Scholar
  245. Thebaudin, J.Y., Lefebvre, A.C., Harrington, M., Bourgeois, C.M. 1997. Dietary fibres: nutritional and technological interest. Trends Food Sci. Technol. 8, 41–48.CrossRefGoogle Scholar
  246. Thelwall, L.A.W. 1997. Lactose: chemical derivatives. In: Advanced Dairy Chemistry (P.F. Fox, ed.), pp. 39– 76, Vol. 3, 2nd Edition, P.F. Fox, ed., Chapman & Hall, London.Google Scholar
  247. Tlaskalova-Hogenova, H., Stepankova, R., Hudcovic, T., Tuckova, L.,Cukrowska, B., Lodinova-Zadnkova, R., Kozakova, H., Rossmann, P., Bartova, J., Sokol, D., Funda, D.P., Borovska, D., Rehakova, Z., Sinkora, J., Hofman, J., Drastich, P., Kokesova, A. 2004. Commensal bacteria (normal microflora), mucosal immunity and chronic inflammatory and autoimmune diseases. Immunol. Lett. 93, 97–108.CrossRefGoogle Scholar
  248. Toba, T., Adachi, S. 1978. Hydrolysis of lactose by microbial β-galactosidases. Formation of oligosaccharide with special reference to 2-O-β-D-galactopyranosyl-D-glucose. J. Dairy Sci. 61, 33–38.CrossRefGoogle Scholar
  249. Toba, T., Tomita, Y., Itoh, T., Adachi, S. 1981. β-Galactosidases of lactic acid bacteria: characterization by oligosaccharides formed during hydrolysis of lactose. J. Dairy Sci. 64, 185–192.CrossRefGoogle Scholar
  250. Toba, T., Yokota, A., Adachi, S. 1985. Oligosaccharide structures formed during the hydrolysis of lactose by Aspergillus oryzae β-galactosidase. Food Chem. 16, 147–162.CrossRefGoogle Scholar
  251. Tomito, M., Shimamura, S., Tamura, Y., Mizota, T., Nakano, S., Suzawa, I. 1994. Crystalline lactulose trihydrate and a method for its manufacture. US Patent 5304251, publication date Apr. 19, 1994, assigned to Morinaga Milk Industry Co., Ltd.Google Scholar
  252. Topping, D.L., Clifton, P.M. 2001. Short-chain fatty acids and human colonic function: roles of resistant starch and nonstarch polysaccharides. Physiol. Rev. 81, 1031–1064.Google Scholar
  253. Townsend, R.R., Hardy, M.R., Hindsgaul, O., Lee, Y.C. 1988. High-performance anion-exchange chromatography of oligosaccharides using pellicular resins and pulsed amperometric detection. Anal. Biochem. 174, 459–470.CrossRefGoogle Scholar
  254. Tuohy, K.M., Ziemer, C.J., Klinder, A., Knobel, Y., Pool-Zobel, B.L., Gibson, G.R. 2002. A human volunteer study to determine the prebiotic effects of lactulose powder on human colonic microbiota. Microbial Ecol. Health Dis. 14, 165–173.CrossRefGoogle Scholar
  255. Tzortzis, G., Goulas, A.K., Gibson, G.R. 2005a. Synthesis of prebiotic galactooligosaccharides using whole cells of a novel strain, Bifidobacterium bifidum NCIMB 41171. Appl. Microbiol. Biotechnol. 68, 412–416.CrossRefGoogle Scholar
  256. Tzortzis, G., Goulas, A.K., Gee, J.M., Gibson, G.R. 2005b. A novel galactooligosaccharide mixture increases the bifidobacterial population numbers in a continuous in vitro fermentation system and in the proximal colonic contents of pigs in vivo. J. Nutr. 135, 1726–1731.Google Scholar
  257. Usui T., Kubota, S., Ohi, H. 1993. A convenient synthesis of β-galactosyl disaccharide derivatives using the β-D-galactosidase from Bacillus circulans. Carbohydr. Res. 244, 315–323.CrossRefGoogle Scholar
  258. Van den Heuvel, E.G., Muijs, T., van Dokkum, W., Schaafsma, G. 1999. Lactulose stimulates calcium absorption in post-menopausal women. J. Bone Mineral Res. 14, 1211–1216.CrossRefGoogle Scholar
  259. Van den Heuvel, E.G., Schoterman, M.H.C., Muijs, T. 2000. Transgalactooligosaccharides stimulate calcium absorption in post-menopausal women. J. Nutr. 130, 2938–2942.Google Scholar
  260. Vanhoutte, T., De Preter, V., De Brandt, E., Verbeke, K., Swings, J., Huys, G. 2006. Molecular monitoring of the fecal microbiota of healthy human subjects during administration of lactulose and Saccharomyces boulardii. Appl. Environ. Microbiol. 72, 5990–5997.CrossRefGoogle Scholar
  261. Van Laere, K.M.J., Abee, T., Schols, H.A., Beldman, G., Voragen, A.G.J. 2000. Characterization of a novel β-galactosidase from Bifidobacterium adolescentis DSM 20083 active towards transgalactooligosaccharides. Appl. Environ. Microbiol. 66, 1379–1384.CrossRefGoogle Scholar
  262. Van Loveren, C. 2004. Sugar alcohols: what is the evidence for caries-preventive and caries-therapeutic effects? Caries Res. 38, 286–293.CrossRefGoogle Scholar
  263. Van Riel, J., Olieman, C. 1991. Selectivity control in the anion-exchange chromatographic determination of saccharides in dairy products using pulsed amperometric detection. Carbohyd. Res. 215, 39–46.CrossRefGoogle Scholar
  264. Van Soest, P.J. 1978. Dietary fibers: their definition and nutritional properties. Am. J. Clin. Nutr. 31 Suppl., S12–S20.Google Scholar
  265. Van Velthuijsen, J.A. 1979. Food additives derived from lactose: lactitol and lactitol palmitate. J. Agric. Food Chem. 27, 680–686.CrossRefGoogle Scholar
  266. Vogt, J.A., Ishii-Schrade, K.B., Pencharz, P.B., Jones, P.J.H., Wolever, T.M.S. 2006. L-Rhamnose and lactulose decrease serum triacylglycerols and their rates of synthesis, but do not affect serum cholesterol concentrations in men. J. Nutr. 136, 2160–2166.Google Scholar
  267. Wallenfels, K. 1951. Enzymatische synthese von oligosacchariden aus disacchariden. Naturwissenschaften 38, 306–307.CrossRefGoogle Scholar
  268. Williams, C.M., Jackson, K.G. 2002. Inulin and oligofructose: effects on lipid metabolism from human studies. Br. J. Nutr. 87, Suppl 2, S261–S264.CrossRefGoogle Scholar
  269. Yanahira, S., Suguri, T., Yakabe, T., Ikeuchi, Y., Hanagata, G., Deya, E. 1992. Formation of oligosaccharides from lactitol by Aspergillus oryzae β-D-galactosidase. Carbohyd. Res. 232, 151–159.CrossRefGoogle Scholar
  270. Yanahira, S., Kobayashi, T., Suguri, T., Nakakoshi, M., Miura, S., Ishikawa, H., Nakajima, I. 1995. Formation of oligosaccharides from lactose by Bacillus circulans β-galactosidase. Biosci. Biotechnol. Biochem. 59, 1021–1026.CrossRefGoogle Scholar
  271. Yazawa, K., Tamura, Z. 1982. Search for sugar sources for selective increase of bifidobacteria. Bifidobacteria Microflora, 1, 34–44.Google Scholar
  272. Yazawa, K., Imai, K., Tamura, Z. 1978. Oligosaccharides and polysaccharides specifically utilizable by bifidobacteria. Chem. Pharm. Bull. (Tokyo) 26, 3306–3311.CrossRefGoogle Scholar
  273. Yoneyama, M., Mandai, T., Aga, H., Fujii, K., Sakai, S., Katayama, Y. 1992. Effects of 4-β-d-galactosylsucrose (lactosucrose) intake on intestinal flora in healthy humans. J. Jap. Soc. Nutr. Food Sci. 45, 101–107.CrossRefGoogle Scholar
  274. Ziegler, E., Vanderhoof, J.A., Petschow, B., Mitmesser, S.H., Stolz, S.I., Harris, C.L., Berseth, C.L. 2007. Term infants fed formula supplemented with selected blends of prebiotics grow normally and have soft stools similar to those reported for breast-fed infants. J. Pediatr. Gastroenterol. Nutr. 44, 359–364.CrossRefGoogle Scholar
  275. Zopf, D., Roth, S. 1996. Oligosaccharide anti-infective agents. Lancet 347, 1017–1021.CrossRefGoogle Scholar

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© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  1. 1.Melbourne BiotechnologyHamptonAustralia
  2. 2.Food Science AustraliaWerribeeAustralia

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