Galacto-oligosaccharides (GOS), also known as oligogalactosyllactose, oligogalactose, oligolactose or transgalactooligosaccharides (TOS), belong to the group of prebiotics. Prebiotics are defined as non-digestible food ingredients that beneficially affect the host by stimulating the growth and/or activity of beneficial bacteria in the colon. GOS occurs in commercial available products such as food for both infants and adults.
The composition of the galacto-oligosaccharide fraction varies in chain length and type of linkage between the monomer units. Galacto-oligosaccharides are produced through the enzymatic conversion of lactose, a component of bovine milk.
A range of factors come into play when determining the yield, style and type of GOS produced. These factors include:
- The enzyme source
- The enzyme dosage
- The feeding stock (Lactose) concentration
- The origins of the lactose
- The process involved (e.g. free or immobilized enzyme)
- The reaction conditions impacting the processing situation
- The medium composition
GOS generally comprise a chain of galactose units that arise through consecutive transgalactosylation reactions, with a terminal glucose unit. However, where a terminal galactose unit is indicated, hydrolysis of GOS formed at an earlier stage in the process has occurred. The degree of polymerization of GOS can vary quite markedly, ranging from 2 to 8 monomeric units, depending mainly on the type of the enzyme used and the conversion degree of lactose.
Commercially available GOS
GOS have been used as food ingredients in Japan and Europe for at least 30 years and their application has expanded rapidly. It all started in Japan, where Japanese companies like Yakult Honsha (Tokyo, Japan) and Nissin Sugar Manufacturing Company (Tokyo, Japan) produced GOS for food applications. Later on Snow Brand Milk Products (Tokyo, Japan), FrieslandCampina Domo (ex Borucolo ingredients and Friesland Foods Domo) in the Netherlands and Clasado Ltd in the United Kingdom also started to produce GOS. In contrast, GOS production in the USA remains negligible. Nowadays, GOS is mostly used for application in infant nutrition.
Most of the manufacturers produce several classes of products in terms of GOS purity in either syrup and/or powder format. Yakult is producing three GOS products: Oligomate 55 in syrup form, Oligomate 55P in powder form and TOS-100 a purified version of 99% oligosaccharide content. Nissin is producing Cup-Oligo in syrup (Cup-Oligo H70) and powder format (Cup-Oligo P) and Snow Brand produces GOS that is incorporated into its infant milk formula P7L, without offering sales outside its organization. In Europe, FrieslandCampina Domo is offering Vivinal GOS in a syrup format containing 57% oligosaccharides on dry matter and in a two powder format containing 29% or 71% oligosaccharides on dry matter. Clasado Ltd is offering a powder GOS product, Bimuno, with 52% galacto-oligosaccharide content on dry matter, as well as a syrup and pastille versions of that product. Besides the differences in purity amongst the commercially offered products, there are differences also in the linkages of the oligosaccharide chain due to the different enzymes used in their production. This can have a direct impact on their potential to affect host's physiology and health. The Oligomate range is produced with enzymes originating from Aspergillus oryzae offering mainly β 1-6 linkages, the Bimuno product is produced using enzymes from a probiotic Bifidobacterium bifidum and contains mainly β 1-3 linkages whilst Cup-Oligo and Vivinal offer mainly β 1-4 linkages as a result of the activity of enzymes from Bacillus circulans for the latter and Cryptococcus laurentii for the former GOS product. Yakult is also considering dual enzymes systems combining the activity of enzymes from A. oryzae and B. circulans to produce GOS mixtures of β 1-4 and β 1-6 linkages.
Health benefits and issues
Because of the configuration of their glycosidic bonds, galacto-oligosaccharides largely resist hydrolysis by salivary and intestinal digestive enzymes. Therefore, they reach the end of the intestine virtually intact. The human intestine contains about 300-500 different species of bacteria that can be divided into health-promoting ones, like Bifidobacteria and Lactobacilli and into harmful ones such as some types of Clostridia. Galacto-oligosaccharides (GOS) are classified as prebiotics, defined as non-digestible food ingredients that beneficially affect the host by stimulating the growth and/or activity of beneficial bacteria in the colon. The increased activity of these health-promoting bacteria results in a number of health-related benefits both directly by the bacteria themselves or indirectly by the organic acids they produce via fermentation. Examples of potential health-promoting benefits are inhibition of the growth of harmful bacteria, stimulation of immune functions, absorption of essential nutrients and syntheses of certain vitamins.
Stimulating health-promoting bacteria
Galacto-oligosaccharides have been shown to be an excellent source for health-promoting bacteria such as Bifidobacteria and Lactobacilli. Many studies with infants and adults have shown that foods or drinks enriched with galacto-oligosaccharides result in a significant increase in Bifidobacteria. In comparison with other oligosaccharides, a large bifidogenic effect was shown for galacto-oligosaccharides. For example, an in vitro study showed that, in comparison to several carbohydrates, galacto-oligosaccharides were shown to support the most favourable growth characteristics for Bifidobacteria and Lactobacilli. However, not all GOS result in the same effect due to differences in their structures as explained above. For example, it was shown that consumption of a galacto-oligosaccharide mixture produced with enzymes originating from bifidobacterial species resulted in an increase in the bifidogenic properties in comparison to a galacto-oligosaccharide mixture produced with another enzyme.
Support of natural defenses
Human gut microbiota play a key role in the intestinal immune system, in maintaining a disease-free state. The gut and immune system form a complex structure that provides defense against ingested toxins and pathogenic bacteria. A well-balanced gut microflora is thought to play a particularly important role in the natural defense of the human body. Galactooligosaccharides support natural defenses of the human body via the gut microflora, indirectly by increasing a number of good bacteria in the gut and inhibiting the binding or survival of Escherichia coli, Salmonella Typhimurium and Clostridia to the body, reducing the chances of getting infected. Furthermore, GOS can positively influence the immune system—indirectly through the production of antimicrobial substances as the result of galactooligosaccharide fermentation, that can reduce the proliferation of pathogenic bacteria, and directly by interaction with immune cells. For example, in infants the usage of GOS has been shown to have a potential role in allergy prevention and reduction of infectious diseases. GOS supplementation has also been shown to reduce symptoms of gastrointestinal dysfunction and reduce the number of days with cold or flu in stressed undergraduate students undergoing exams.
Improvement of mineral absorption
While calcium is necessary for processes such as bone development, only part of the calcium present in the diet is available for absorption. GOS can contribute to the provision of sufficient levels of calcium as it stimulates its absorption. In humans it has been demonstrated that the consumption of GOS significantly increases calcium absorption. In animal studies it has been demonstrated that administration of galacto-oligosaccharides results in more efficiently absorbed calcium and increased bone density, indicating the prevention of bone losses. Not only calcium absorption is positively influenced, there are indications that the absorption of magnesium can be improved as well.
Relief of constipation
Constipation is a frequent problem, particularly among infants, elderly and pregnant women. In infants, formula feeding is associated with constipation and hard stools. For those suffering from constipation, consumption of galacto-oligosaccharides can offer relief to their constipation. It has been shown that galacto-oligosaccharides increase frequency of defecation, soften the stools and improve stool consistency.
GOS is a prebiotic. The main similarity between pre- and probiotics is that they both result in beneficial effects to the host after consumption. Combinations of pre- and probiotics with synergistic effects are often referred to as synbiotics. Clinical studies with infants and children indicated that addition of galacto-oligosaccharides to a probiotic mixture resulted in higher numbers of Bifidobacteria and increased resistance to respiratory infections during the first two years of life as compared to only the probiotic. In this way, GOS can enhance the effect of a probiotic.
FODMAP and flatulence
Galacto-oligosaccharides are selectively fermented by colonic bacteria. All these bacteria produce gas at fermentation. The fermentatiion of galacto-oligosaccharides, mainly by bifidobacteria, produces the least volume of gas, compared to other prebiotic oligosaccharides. They do not contribute to flatulence and gastrointestinal discomfort, when taken at the recommended dose. For this reason, they are not classed as FODMAPs and should not be restricted on the low-FODMAP diet, contrary to fructose, fructans and alpha-linked galactose-containing oligosaccharides such as those found in various legumes and beans. Excessive intake can, however, contribute to loss of specificity leading to fermentation by a number of other colonic bacteria that do produce more gas.
- Xylooligosaccharide (XOS)
- Gibson GR (October 1998). "Dietary modulation of the human gut microflora using prebiotics". Br. J. Nutr. 80 (4): S209–12. PMID 9924286.
- Roberfroid MB (June 2000). "Prebiotics and probiotics: are they functional foods?". Am. J. Clin. Nutr. 71 (6 Suppl): 1682S–7S; discussion 1688S–90S. PMID 10837317.
- Macfarlane GT, Steed H, Macfarlane S (February 2008). "Bacterial metabolism and health-related effects of galacto-oligosaccharides and other prebiotics". J. Appl. Microbiol. 104 (2): 305–44. doi:10.1111/j.1365-2672.2007.03520.x. PMID 18215222.
- Bouhnik Y, Raskine L, Simoneau G et al. (December 2004). "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 (6): 1658–64. PMID 15585783.
- Ito, M., Deguchi, Y., Matsumoto, K., Kimura, M. Onodera, N., Yajima, T. (1993b) Influence of galactooligosaccharides on the human fecal microflora. J Nutr Sci Vitaminol. 39, 635-640
- Silk DB, Davis A, Vulevic J, Tzortzis G, Gibson GR (March 2009). "Clinical trial: the effects of a trans-galactooligosaccharide prebiotic on faecal microbiota and symptoms in irritable bowel syndrome". Aliment. Pharmacol. Ther. 29 (5): 508–18. doi:10.1111/j.1365-2036.2008.03911.x. PMID 19053980.
- Vulevic J, Drakoularakou A, Yaqoob P, Tzortzis G, Gibson GR (November 2008). "Modulation of the fecal microflora profile and immune function by a novel trans-galactooligosaccharide mixture (B-GOS) in healthy elderly volunteers". Am. J. Clin. Nutr. 88 (5): 1438–46. PMID 18996881.
- Ben XM, Zhou XY, Zhao WH et al. (June 2004). "Supplementation of milk formula with galacto-oligosaccharides improves intestinal micro-flora and fermentation in term infants". Chin. Med. J. 117 (6): 927–31. PMID 15198901.
- Boehm G, Lidestri M, Casetta P et al. (May 2002). "Supplementation of a bovine milk formula with an oligosaccharide mixture increases counts of faecal bifidobacteria in preterm infants". Arch. Dis. Child. Fetal Neonatal Ed. 86 (3): F178–81. PMC 1721408. PMID 11978748.
- Fanaro S, Marten B, Bagna R et al. (January 2009). "Galacto-oligosaccharides are bifidogenic and safe at weaning: a double-blind randomized multicenter study". J. Pediatr. Gastroenterol. Nutr. 48 (1): 82–8. doi:10.1097/MPG.0b013e31817b6dd2. PMID 19172129.
- Napoli JE, Brand-Miller JC, Conway P (November 2003). "Bifidogenic effects of feeding infant formula containing galacto-oligosaccharides in healthy formula-fed infants". Asia Pac J Clin Nutr 12 (Suppl): S60. PMID 15023687.
- Watson, D; O'Connell Motherway M, Schoterman MHC, et al (2013). "Selective carbohydrate utilization by lactobacilli and bifidobacteria". Journal of Applied Microbiology 114 (4): 1132–46. doi:10.1111/jam.12105.
- Depaint, F; Tzortzis G; Vulevic J et al. (2008). "Prebiotic evaluation of a novel galactooligosaccharide mixture produced by the enzymatic activity of Bifidobacterium bifidum NCIMB 41171, in healthy humans:a randomized, double-blind, cross-over, placebo-controlled intervention study". American Journal of Clinical Nutrition 87: 785–791.
- Gibson, G.R., McCartney, A.L., Rastall, R.A. (2005) Prebiotics and resistance to gastrointestinal infections. Br J of Nutr. 93, Suppl. 1, pp31-34.
- Shoaf, K., Muvey, G.L., Armstrong, G.D., Hutkins, R.W. (2006) Prebiotic galactooligosaccharides reduce adherence of enteropathogenic Escherichia coli to tissue culture cells. Infect Immun. Dec;74(12):6920-8.
- Searle LEJ, Best A, Nunez A, Salguero FJ, Johnson L, Weyer U, Dugdale AH, Cooley WA, Carter B, Jones G, Tzortis G, Woodward MJ and La Ragione RM (2009); A mixture containing galactooligosaccharides, produced by enzymatic activity of Bifidobacterium bifidum, reduces Salmonella enterica serovar Typhimurium infection; J of Med Micro; 58; 37-48
- Rada V, Nevoral J, Trojanová I, Románková E, Ŝmehilová M and Killer J (2008); Growth of infant faecal Bifidobacteria and clostridia on prebiotic oligosaccharides in in vitro conditions; Anaerobe 14; 205-208.
- Sinclair HR, de SJ, et al.(2009); Galactooligosaccharides (GOS) inhibit Vibrio cholerae toxin binding to its GM1 receptor. Journal of Agricultural and Food Chemistry 57(8);3113-3119
- Macfarlane GT, Steed H, et al. (2008);Bacterial metabolism and health-related effects of galacto-oligosaccharides and other prebiotics;Journal of Applied Microbiology 104(2);305-344
- Vos AP, M'Rabet L, et al. (2007);Immune-modulatory effects and potential working mechanisms of orally applied nondigestible carbohydrates;Critical Reviews in Immunology 27(2);97-140
- Gopalakrishnan A, Clinthorne JF, et al. (2012); Supplementation with Galacto-Oligosaccharides increases the percentage of NK cells and reduces colitis severity in Smad3-deficient mice;Journal of Nutrition142;1336-1342
- Van Hoffen E, Ruiter B, et al.(2009); A specific mixture of short-chain galactooligosaccharides and longchain fructooligosaccharides induces a beneficial immunoglobulin profile in infants at high risk for allergy; Allergy 64;484-487
- Schouten B, van Esch BCAM, et al.(2009);Cow milk allergy symptoms are reduced in mice fed dietary synbiotics during oral sensitization with whey.Journal of Nutrition 139;1398-1403
- Bakker-Zierikzee AM, Tol EA(2006);Faecal SigA secretion in infants fed on pre-or probiotic infant formula; Pediatric Allergy and Immunology 17(2);134-40
- Arslanoglu, S., Moro, G.E., Schmitt, J., Tandoi, L., Rizzardi, S., Boehm, G. (2008) Early dietary intervention with a mixture of prebiotic oligosaccharides reduces the incidence of allergic manifestations and infections during the first two years of life. J of Nutr 138(6);1091-1095.
- Bruzzese E, Volpicelli M, Squeglia V, Bruzzese D, Salvini F, Bisceglia M, Lionetti P, Cinquetti M, Iacono G, Amarri S and Guarino A (2009); A formula containing galacto- an fructo-oligosacchairdes prevents intestinal and extra-intestinal infections: An observational study; Clinical Nutrition ; 1-6
- Hughes, C., Davoodi-Semiromi, Y., Colee, J.C., Culpepper, T., Dahl, W.J., Mai, V., Christman, M.C., Langkamp-Henken, B. (2011); Galactooligosaccharide supplementation reduces stress-induced gastrointestinal dysfunction and days of cold or flu: a randomized, double-blind, controlled trial in healthy university students. Am J Clin Nutr 93(6);1305-11.
- Whisner CM, Martin BR, et al (2013);Galacto-oligosaccharides increase calcium absorption and gut bifidobacteria in young girls: a double-blind cross-over trial;British Journal of Nutrition 110(7);1292-303
- Heuvel, van den, E.G.H.M., Schoterman, M.H.C., Muijs, T.(2000) Transgalactooligosaccharides stimulate calcium absorption in postmenopausal women. J. Nutr. 130:2938-2942
- Chonan, O., Watanuki, M. (1995) Effect of galactooligosaccharides on calcium absorption in rats. J. Nutr. Sci. Vitaminol. 41, 95-104.
- Weaver, CM, Martin, BR, Nakatsu, CH, et al.(2011) Galactooligosaccharides improve mineral absorption and bone properties in growing rats trough gut fermentation;Journal of Agricultural and Food Chemistry 59(12);6501-10
- Quinlan, PT, Lockton, S, et al.(1995);The relationship between stool hardness and stool composition in breast- and formula-fed infants; Journal of Pediatric Gastroenterology and Nutrition 20(1);81-90
- Deguchi, Y., Matsumoto, K., Ito, A., Watanuki, M. (1997) Effects of beta 1-4 galactooligosaccharides administration on defeacation of healthy volunteers with a tendency to constipation. Jap J of Nutr. 55(1), 13-22.
- Teuri, U., Korpela, R. (1998) Galacto-oligosaccharides relieve constipation in elderly people. Ann Nutr Metabolism. 42, 319-327.
- Schmelze, H, Wirth, S, et al.(2003);Randomized double-blind study of the nutritional efficacy and bifidogenicity of a new infant formula containing partially hydrolyzed protein, a high beta-palmitic acid level, and nondigestible oligosaccharides;Journal of Pediatric Gastroenterology and Nutrition36(3);343-351
- Costalos, C, Kapiki, A, et al.(2008);The effect of a prebiotic supplemented formula on growth and stool microbiology of term infants; Early Human Development 84(1);45-49
- Ben, XM, Zhou, XY, et al.(2004);Supplementation of milk formula with galacto-oligosaccharides improves intestinal micro-flora and fermentation in term infants; Chinese Medical Journal (Engl) 117(6);927-931
- Moro, G, Minoli, I, et al.(2002);Dosage-related bifidogenic effects of galacto- and fructooligosaccharides in formula-fed term infants;Journal of Pediatric Gastroenterology and Nutrition 34(3);291-295
- Boehm, G, Lidestri, M, et al.(2002);Supplementation of a bovine milk formula with an oligosaccharide mixture increases counts of faecal bifidobacteria in preterm infants; Archives of Disease in Childhood - Fetal and Neonatal Edition 86(3);F178-F181
- Ashley, C, Johnston, WH, et al.(2012);Growth and tolerance of infants fed formula supplemented with polydextrose (PDX) and/ or galactooligosaccharides (GOS): double-blind, randomized, controlled trial. Nutrition Journal 11(38)
- Kukkonen, K. et al. Long-term safety and impact on infection rates of postnatal probiotic and prebiotic (synbiotic) treatment: randomized, double-blind, placebo-controlled trial (2008). Pediatrics;122 (1):8-12.
- Piirainen, L., Kekkonen, R.A., Kajander, K., Ahlroos, T., Tynkkynen, S., Nevala, R., Korpela, R. (2008) In school-aged children a combination of galactooligosaccharides and Lactobacillus GG increases bifidobacteria more than Lactobacillus GG on its own. (2008) Ann Nutr Metab;52(3):204-8
- Rycroft, CE, Jones, MR,Gibson, GR, Rastall, RA.(2001);A comparative in vitro evaluation of the fermentation properties of prebiotic oligosaccharides; Journal of Applied Microbiology91;878-887