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Inulin, oligofructose and immunomodulation

Published online by Cambridge University Press:  08 March 2007

Bernhard Watzl*
Institute of Nutritional Physiology, Federal Research Centre for Nutrition and Food, Haid-und-Neu-Strasse 9, 76131, Karlsruhe, Germany
*Corresponding author: Dr Bernhard Watzl, fax +49 721 6625 404, email
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Diet is known to modulate immune functions in multiple ways and to affect host resistance to infections. Besides the essential nutrients, non-essential food constituents such as non-digestible carbohydrates may also have an impact on the immune system, especially in the area of the gut-associated lymphoid tissue (GALT). Recent data now provide first evidence that prebiotics such as inulin/oligofructose (IN/OF) modulate functions of the immune system. In animal studies IN/OF primarily activated immune cells in Peyer's patches including IL-10 production and natural killer (NK) cell cytotoxicity. Other immune functions modulated by IN/OF included the concentration of secretory IgA in ileum and caecum, splenic NK cell cytotoxicity as well as splenocyte cytokine production. In different tumour models, a lower incidence of tumours was observed, which in the case of colonic tumours was associated with enhanced NK cell cytotoxicity in the GALT. Few human studies so far have investigated the effects of IN/OF alone or in combination with other dietary supplements on immunocompetence. Supplementation of IN/OF resulted in minor changes of systemic immune functions such as decrease in phagocytic activity. No data are available on the effects of IN/OF on the GALT in man. The mechanisms of the reported effects of IN/OF on the immune system are currently investigated and include: (i) direct effects of lactic acid-producing bacteria or bacterial constituents on immune cells; (ii) the production of SCFA and binding to SCFA receptors on leucocytes. In conclusion, the current data suggest that IN/OF primarily modulate immune parameters in the GALT, but splenocytes are also activated by IN/OF. Human studies are needed to find out whether IN/OF have the potential to modulate systemic immunity in wellnourished individuals and to lower the risk of diseases such as colon cancer.

Research Article
Copyright © The Nutrition Society 2005


Abreu, MT (2003) Immunologic regulation of toll-like receptors in gut epithelium. Curr Opin Gastroenterol 19, 559564.CrossRefGoogle ScholarPubMed
Abreu-Martin, MT & Targan, SR (1996) Regulation of immune responses of the intestinal mucosa. Crit Rev Immunol 16, 277309.CrossRefGoogle ScholarPubMed
Akira, Sh, Takeda, K & Kaisho, T (2001) Toll-like receptors: critical proteins linking innate and acquired immunity. Nat Immunol 2, 675680.CrossRefGoogle ScholarPubMed
Bach Knudsen, SE, Serena, A, Canibe, N & Juntunen, KS (2003) New insight into butyrate metabolism. Proc Nutr Soc 62, 8186.CrossRefGoogle ScholarPubMed
Bassonga, E, Forest, V, Pierre, F, Bornet, F, Perrin, P, Meflah, K & Menanteau, J (2001) Cytokine mRNA expression in mouse colon: IL-15 mRNA is overexpressed and is highly sensitive to a fibre-like dietary component (short-chain fructo-oligosaccharides) in an Apc gene manner. Cytokine 14, 243246.CrossRefGoogle Scholar
Bouhnik, Y, Vahedi, K, Achour, L, et al. (1999) Short-chain fructo-oligosaccharide administration dose-dependently increases fecal bifidobacteria in healthy humans. J Nutr 129, 113116.CrossRefGoogle ScholarPubMed
Brown, AJ, Goldsworthy, SM, Barnes, AA, et al. (2003) The orphan G protein-coupled receptors GPR41 and GPR43 are activated by propionate and other short chain carboxylic acids. J Biol Chem 278, 1131211319.CrossRefGoogle ScholarPubMed
Brown, GD & Gordon, S (2001) A new receptor for β-glucans. Nature 413, 3637.CrossRefGoogle ScholarPubMed
Buddington, KK, Donahoo, JB & Buddington, RK (2002) Dietary oligofructose and inulin protect mice from enteric and systemic pathogens and tumor inducers. J Nutr 132, 472477.CrossRefGoogle ScholarPubMed
Bunout, D, Hirsch, S, de la Maza, MP, et al. (2002) Effects of prebiotics on the immune response to vaccination in the elderly. J Parenter Enteral Nutr 26, 372376.CrossRefGoogle ScholarPubMed
Calder, PC, Field, CJ & Gill, HS (2002) Nutrition and Immune Function, Wallingford, UK: CABI Publishing.CrossRefGoogle Scholar
Cavaglieri, CR, Nishiyama, A, Fernandes, LC, Curi, R, Miles, EA & Calder, PC (2003) Differential effects of short-chain fatty acids on proliferation and production of pro- and anti-inflammatory cytokines by cultured lymphocytes. Life Sci 73, 16831690.CrossRefGoogle ScholarPubMed
Cherayil, BJ (2003) How not to get bugged by bugs: mechanisms of cellular tolerance to microorganisms. Curr Opin Gastroenterol 19, 572577.CrossRefGoogle ScholarPubMed
Chiang, BL, Sheih, YH, Wang, LH, Liao, CK & Gill, HS (2000) Enhancing immunity by dietary consumption of a probiotic lactic acid bacterium ( Bifidobacterium lactis HN019): optimization and definition of cellular immune responses. Eur J Clin Nutr 54, 849855.CrossRefGoogle ScholarPubMed
Delzenne, NM (2003) Oligosaccharides: state of the art. Proc Nutr Soc 62, 177182.CrossRefGoogle ScholarPubMed
Duggan, Ch, Penny, ME, Hibberd, P, Gil, A, Huapaya, A, Cooper, A, Coletta, F, Emenhiser, C & Kleinman, RE (2003) Oligofructose-supplemented infant cereal: 2 randomized, blinded, community-based trials in Peruvian infants. Am J Clin Nutr 77, 937942.CrossRefGoogle ScholarPubMed
Engelhardt, W, Busche, R, Gross, G & Rechkemmer, G (1991) Absorption of short chain fatty acids: mechanisms and regional differences in the large intestine. In Physiological and Clinical Aspects of Short-Chain Fatty Acids pp. 6062 [Cummings, JH, Rombeau, JL and Sakata, T, editors]. Cambridge, UK: Cambridge University Press.Google Scholar
Femia, AP, Luceri, C, Dolara, P, et al. (2002) Antitumorigenic activity of the prebiotic inulin enriched with oligofructose in combination with the probiotics Lactobacillus rhamnosus and Bifidobacterium lactis on azoxymethane-induced colon carcinogenesis in rats. Carcinogenesis 23, 19531960.CrossRefGoogle ScholarPubMed
Field, CJ, McBurney, MI, Massimino, S, Hayek, MG & Sunvold, GD (1999) The fermentable fiber content of the diet alters the function and composition of canine gut associated lymphoid tissue. Vet Immunol Immunopathol 72, 325341.CrossRefGoogle ScholarPubMed
Flickinger, EA, Van Loo, J & Fahey, GC (2003) Nutritional responses to the presence of inulin and oligofructose in the diets of domesticated animals: a review. Crit Rev Food Sci Nutr 43, 1960.CrossRefGoogle ScholarPubMed
Franck, A (2002) Technological functionality of inulin and oligofructose. Br J Nutr 87, S287S291.CrossRefGoogle ScholarPubMed
Fukushima, Y, Kawata, Y, Mizumachi, K, Kurisaki, J & Mitsuoka, T (1999) Effect of bifidobacteria feeding on fecal flora and production of immunoglobulins in lactating mouse. Int J Food Microbiol 46, 193197.CrossRefGoogle ScholarPubMed
Gaskins, HR, Mackie, RI, May, T & Garleb, KA (1996) Dietary fructo-oligosaccharide modulates large intestinal inflammatory responses to Clostridium difficile in antibiotic-compromised mice. Microb Ecol Health Dis 9, 157166.CrossRefGoogle Scholar
Gibson, GR & Roberfroid, MB (1995) Dietary modulation of the human colonic microbiota: introducing the concept of prebiotics. J Nutr 125, 14011412.Google ScholarPubMed
Gibson, GR, Beatty, EB, Wang, X & Cummings, JH (1995) Selective stimulation of bifidobacteria in the human colon by oligofructose and inulin. Gastroenterology 108, 975982.CrossRefGoogle ScholarPubMed
Grizard, D & Barthomeuf, Ch (1999) Non-digestible oligosaccharides used as prebiotic agents: mode of production and beneficial effects on animal and human health. Reprod Nutr Dev 39, 563588.CrossRefGoogle ScholarPubMed
Guigoz, Y, Rochat, F, Perruisseau-Carrier, G, Rochat, I & Schiffrin, EJ (2002) Effects of oligosaccharide on the faecal flora and non-specific immune system in elderly people. Nutr Res 22, 1325.CrossRefGoogle Scholar
Herich, R, Révajová, V, Levkut, M, Bomba, A, Nemcová, R, Guba, P & Gancarčiková, S (2002) The effect of Lactobacillus paracasei and Raftilose P95 upon the non-specific immune response of piglets. Food Agric Immunol 14, 171179.CrossRefGoogle Scholar
Herre, J, Gordon, S & Brown, GD (2004) Dectin-1 and its role in the recognition of β-glucans by macrophages. Mol Immunol 40, 869876.CrossRefGoogle ScholarPubMed
Hosono, A, Ozawa, A, Kato, R, Ohnishi, Y, Nakanishi, Y, Kimura, T, Nakamura, R (2003) Dietary fructooligosaccharides induce immunoregulation of intestinal IgA secretion by murine Peyer's patch cells. Biosci Biotechnol Biochem 67, 758764.CrossRefGoogle ScholarPubMed
Howard, MD, Gordon, DT, Garleb, KA & Kerley, MS (1995) Dietary fructooligosaccharide, xylooligosaccharide and gum arabic have variable effects on cecal and colonic microbiota and epithelial cell proliferation in mice and rats. J Nutr 125, 26042609.Google ScholarPubMed
Ichikawa, H, Shineha, R, Satomi, S & Sakata, T (2002) Gastric or rectal instillation of short-chain fatty acids stimulates epithelial cell proliferation of small and large intestine in rats. Dig Dis Sci 47, 11411146.CrossRefGoogle ScholarPubMed
Iijima, H, Takahashi, I & Kiyono, H (2001) Mucosal immune network in the gut for the control of infectious diseases. Rev Med Virol 11, 117133.CrossRefGoogle ScholarPubMed
Inan, MS, Rasoulpour, RJ, Yin, L, Hubbard, RK, Rosenberg, DW & Giardina, C (2000) The luminal short-chain fatty acid butyrate modulates NF-kappaB activity in a human colonic epithelial cell line. Gastroenterology 118, 724734.CrossRefGoogle Scholar
Ishizaka, S, Kikuchi, E & Tsujii, T (1993) Effects of acetate on human immune system. Immunopharmacol Immunotoxicol 15, 151162.CrossRefGoogle ScholarPubMed
Janeway, CA, Travers, P, Walport, W & Shlonichik, M (2001) Immunobiology. In The Immune System in Health and Disease, 5th ed. New York: Taylor & Francis Books.Google Scholar
Jankovic, D, Liu, Z & Gause, WC (2001) Th1- and Th2-cell commitment during infectious disease: asymmetry in divergent pathways. Trends Immunol 22, 450457.CrossRefGoogle ScholarPubMed
Kaur, N & Gupta, AK (2002) Applications of inulin and oligofructose in health and nutrition. J Biosci 27, 703714.CrossRefGoogle ScholarPubMed
Kelly-Quagliana, KA, Nelson, PD & Buddington, RK (2003) Dietary oligofructose and inulin modulate immune functions in mice. Nutr Res 23, 257267.CrossRefGoogle Scholar
Kripke, SA, Fox, AD, Berman, JM, Settle, RG & Rombeau, JL (1989) Stimulation of intestinal mucosal growth with intracolonic infusion of short-chain fatty acids. J Parenter Enteral Nutr 13, 109116.CrossRefGoogle ScholarPubMed
Kudoh, K, Shimizu, J, Wada, M, Takita, T, Kanke, Y & Innami, S (1998) Effect of indigestible saccharides on B lymphocyte response of intestinal mucosa and cecal fermentation in rats. J Nutr Sci Vitaminol 44, 103112.CrossRefGoogle Scholar
Kudoh, K, Shimizu, J, Ishiyama, A, Wada, M, Takita, T, Kanke, Y & Innami, S (1999) Secretion and excretion of immunoglobulin A to cecum and feces differ with type of indigestible saccharides. J Nutr Sci Vitaminol 45, 173181.CrossRefGoogle ScholarPubMed
Kurita-Ochiai, T, Amano, S, Fukushima, K & Ochiai, K (2003) Cellular events involved in butyric acid-induced T cell apoptosis. J Immunol 171, 35763584.CrossRefGoogle ScholarPubMed
Le Poul, E, Loison, C, Struyf, S, et al. (2003) Functional characterization of human receptors for short chain fatty acids and their role in polymorphonuclear cell activation. J Biol Chem 278, 2548125489.CrossRefGoogle ScholarPubMed
Lim, BO, Yamada, K, Nonaka, M, Kuramoto, Y, Hung, P & Sugano, M (1997) Dietary fibers modulate indices of intestinal immune function in rats. J Nutr 127, 663667.CrossRefGoogle ScholarPubMed
MacDonald, TT (2003) The mucosal immune system. Parasite Immunol 25, 235246.CrossRefGoogle ScholarPubMed
McGuirk, P & Mills, KHG (2002) Pathogen-specific regulatory T cells provoke a shift in the Th1/Th2 paradigm in immunity to infectious diseases. Trends Immunol 23, 450455.CrossRefGoogle ScholarPubMed
Manhart, N, Spittler, A, Bergmeister, H, Mittlböck, M & Roth, E (2003) Influence of fructooligosaccharides on Peyer's patch lymphocyte numbers in healthy and endotoxemic mice. Nutrition 19, 657660.CrossRefGoogle ScholarPubMed
Mowat, AMcI (2003) Anatomical basis of tolerance and immunity in intestinal antigens. Nat Rev Immunol 3, 331341.CrossRefGoogle ScholarPubMed
Mowat, AMcI & Viney, JL (1997) The anatomical basis of intestinal immunity. Immunol Rev 156, 145166.CrossRefGoogle ScholarPubMed
Murosaki, S, Muroyama, K, Yamamoto, Y, Kusaka, H, Liu, T & Yoshika, Y (1999) Immunopotentiating activity of nigerooligosaccharides for the T helper 1-like immune response in mice. Biosci Biotechnol Biochem 63, 373378.CrossRefGoogle Scholar
Nilsson, NE, Kotarsky, K, Owman, C & Olde, B (2003) Identification of a free fatty acid receptor, FFA2R, expressed on leucocytes and activated by short-chain fatty acids. Biochem Biophys Res Commun 303, 10471052.CrossRefGoogle ScholarPubMed
Pierre, F, Perrin, P, Champ, M, Bornet, F, Meflah, K & Menanteau, J (1997) Short-chain fructo-oligosaccharides reduce the occurrence of colon tumors and develop gut-associated lymphoid tissue in Min mice. Cancer Res 57, 225228.Google ScholarPubMed
Pierre, F, Perrin, P, Bassonga, E, Bornet, F, Meflah, K & Menanteau, J (1999) T cell status influences colon tumor occurrence in Min mice fed short chain fructo-oligosaccharides as a diet supplement. Carcinogenesis 20, 19531956.CrossRefGoogle Scholar
Pratt, VC, Tappenden, KA, McBurney, MI & Field, CJ (1996) Short-chain fatty acid-supplemented total parenteral nutrition improves nonspecific immunity after intestinal resection in rats. J Parenter Enteral Nutr 20, 264271.CrossRefGoogle ScholarPubMed
Qiao, H, Duffy, LC, Griffiths, E, Dryja, D, Leavens, A, Rossman, J, Rich, G, Riepenhoff-Talty, M & Locniskar, M (2002) Immune responses in rhesus rotavirus-challenged Balb/c mice treated with bifidobacteria and prebiotic supplements. Pediatr Res 51, 750755.CrossRefGoogle ScholarPubMed
Roller, M, Rechkemmer, G & Watzl, B (2004a) Prebiotic inulin enriched with oligofructose in combination with the probiotics Lactobacillus rhamnosus and Bifidobacterium lactis modulates intestinal immune functions in rats. J Nutr 134, 153156.CrossRefGoogle ScholarPubMed
Roller, M, Femia, AP, Caderni, G & Rechkemmer, G, Watzl, B (2004b) Intestinal immunity of rats with azoxymethane-induced colon cancer is modulated by inulim enriched with oligofructose combined with Lactobacillus rhamnosus and Bifidobacterium longis. Br J Nutr 92, 931938.CrossRefGoogle Scholar
Ross, GD & Větvička, V (1993) CR3 (CD11b, CD18): a phagocyte and NK cell membrane receptor with multiple ligand specificities and functions. Clin Exp Immunol 92, 181184.CrossRefGoogle ScholarPubMed
Säemann, MD, Böhmig, GA, Österreicher, CH, Burtscher, H, Parolini, O, Diakos, Ch, Stöckl, J, Hörl, WH & Zlabinger, GJ (2000) Anti-inflammatory effects of sodium butyrate on human monocytes: potent inhibition of IL-12 and up-regulation of IL-10 production. FASEB J 14, 23802382.CrossRefGoogle ScholarPubMed
Schley, PD & Field, CJ (2002) The immune-enhancing effects of dietary fibres and prebiotics. Br J Nutr 87, S221S230.CrossRefGoogle ScholarPubMed
Schneeman, BO (1999) Fiber, inulin and oligofructose: similarities and differences. J Nutr 129, 1424S – 1427S.CrossRefGoogle ScholarPubMed
Sehgal, G, Zhang, K, Todd, RF 3rd, Boxer, LA, Petty, HR (1993) Lectin-like inhibition of immune complex receptor-mediated stimulation of neutrophils. Effects on cytosolic calcium release and superoxide production. J Immunol 150, 45714580.Google ScholarPubMed
Sheih, YH, Chiang, BL, Wang, LH, Liao, CK & Gill, HS (2001) Systemic immunity-enhancing effects in healthy subjects following dietary consumption of the lactic acid bacterium Lactobacillus rhamnosus HN001. J Am College Nutr 20, 149156.CrossRefGoogle ScholarPubMed
Spahn, TW & Kucharzik, T (2004) Modulating the intestinal immune system: the role of lymphotoxin and GALT organs. Gut 53, 456465.CrossRefGoogle ScholarPubMed
Speert, DP, Eftekhar, F & Puterman, ML (1984) Nonopsonic phagocytosis of strains of Pseudomonas aeruginosa from cystic fibrosis patients. Infect Immun 43, 10061011.Google ScholarPubMed
Swanson, KS, Grieshop, ChM, Flickinger, EA, Bauer, LL, Healy, HP, Dawson, KA, Merchen, NR & Fahey, GC Jr (2002) Supplemental fructooligosaccharides and mannanoligosaccharides influence immune function, ileal and total tract nutrient digestibilities, microbial populations and concentrations of protein catabolites in the large bowel of dogs. J Nutr 132, 980989.CrossRefGoogle ScholarPubMed
Takahashi, T, Nakagawa, E, Nara, T, Yajima, T & Kuwata, T (1998) Effects of orally ingested Bifidobacterium longum on the mucosal IgA response of mice to dietary antigens. Biosci Biotechnol Biochem 62, 1015.CrossRefGoogle ScholarPubMed
van Loo, J, Coussement, P, De Leenheer, L, Hoebregs, H & Smits, G (1995) On the presence of inulin and oligofructose as natural ingredients in the Western diet. Crit Rev Food Sci Nutr 35, 525552.CrossRefGoogle ScholarPubMed
van Loo, J, Cummings, J, Delzenne, N, et al. (1999) Functional food properties of non-digestible oligosaccharides: a consensus report from the ENDO project (DGXII AIRII-CT94-1095). Br J Nutr 81, 121132.Google Scholar
Watzl, B, Bub, A, Blockhaus, M & Herbert, BM, Lührmann, PM, Neuhäuser-Berthold, M, Rechkemmer, G (2000) Prolonged tomato juice consumption has no effect on cell-mediated immunity of well-nourished elderly men and women. J Nutr 130, 17191723.CrossRefGoogle ScholarPubMed
Wolever, TM, Josse, RG, Leiter, RA & Chiasson, JL (1997) Time of day and glucose tolerance status affect serum short-chain fatty acid concentrations in humans. Metabolism 46, 805811.CrossRefGoogle ScholarPubMed
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