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Experimental evidences on the potential of prebiotic fructans to reduce the risk of colon cancer

Published online by Cambridge University Press:  09 March 2007

B. Pool-Zobel ,
J. van Loo ,
I. Rowland  and
M. B. Roberfroid
B. Pool-Zobel*
Affiliation:
Institute for Nutrition, Department of Nutritional Toxicology, Friedrich Schiller University Jena, Dornburger Street 25, 07743 Jena, Germany
J. van Loo
Affiliation:
ORAFTI, Aandorenstraat 1, 3300 Tienen, Belgium
I. Rowland
Affiliation:
University of Ulster, Coleraine, Co Londonderry BT52 ISA, UK
M. B. Roberfroid
Affiliation:
Rue du Rondia 7A, 1348 Louvain-la-Neuve, Belgium
*
*Corresponding author: Prof. Dr. rer. nat. Beatrice L. Pool-Zobel, tel +49 3641 949670, fax +49 3641 949672, email [email protected]
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Abstract

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Inulin is extracted from the chicory root. It is a set of fructans with its monomers (n=2–65) linked by means of β(2–1) bonds. This linkage cannot be hydrolysed by either pancreatic or by brush border digestive enzymes in the upper intestinal tract of humans. As such the carbohydrates arrive in the colon, where they are fermented by bifidobacteria and other lactic acid producing bacteria, thus enhancing their relative populations in the gut. Recent research in experimental animal models revealed that inulin has significant anticarcinogenic properties. It acts chemopreventively by reducing the incidence of azoxymethane (AOM) — induced aberrant crypt foci and tumours in the colon. These effects may be due to the stimulation of bifidobacteria, which themselves have been shown to act as antigenotoxic in the colon and to reduce AOM-induced tumours. Also fermentation products, including the short-chain fatty acid butyrate, could contribute to the protective effects. In this case a mechanism may be the induction of apoptosis of already transformed cells. The experimental evidence from animal studies and from studies elucidating potential mechanisms strongly supports the possibility that inulin will contribute to reducing risks for colon cancer in humans. In order to obtain more insight into this possibility, human dietary intervention studies relating biomarkers of reduced risk to inulin consumption are needed.

Keywords

InulinOligofructoseAberrant cryptsChemopreventionAnticarcinogenic food ingredients
Type
Research Article
Information
British Journal of Nutrition , Volume 87 , Issue S2 , May 2002 , pp. S273 - S281
Copyright
Copyright © The Nutrition Society 2002

References

Abrahamse, SL, Pool-Zobel, BL & Rechkemmer, G (1999) Potential of short chain fatty acids to modulate the induction of DNA damage and changes in the intracellular calcium concentration in isolated rat colon cells. Carcinogenesis 20, 629–634.CrossRefGoogle Scholar
Acheson, ED, Hadfield, EH & Macbeth, RG (1967) Carcinoma of the nasal cavity and accessory sinuses in woodworkers. The Lancet 2/11, 311–312.CrossRefGoogle Scholar
Awasthi, YC, Sharma, R & Singhal, SS (1994) Human glutathione S-transferases. International Journal of Biochemistry 26, 295–308.CrossRefGoogle ScholarPubMed
Ballongue, J, Schumann, C & Quignon, P (1997) Effects of lactulose and lactitol on colonic microflora and enzymatic activity. Scandinavian Journal of Gastroenterology 32, Suppl. 222, 41–44.CrossRefGoogle Scholar
Bird, RP (1987) Observation and quantification of aberrant crypts in the murine colon treated with a colon carcinogen: preliminary findings. Cancer Letters 37, 147–151.CrossRefGoogle ScholarPubMed
Bolognani, F, Rumney, CJ, Coutts, JT, Pool-Zobel, BL & Rowland, IR (2001) Effect of lactobacilli, bifidobacteria and inulin on the formation of aberrant crypt foci in rats. European Journal of Nutrition 40, 293–300.CrossRefGoogle ScholarPubMed
Cohen, JJ (1993) Apoptosis. Immunology Today 14, 126–130.CrossRefGoogle ScholarPubMed
Coles, B, Yang, M, Lang, NP & Kadlubar, FF (2000) Expression of hGSTP1 alleles in human lung and catalytic activity of the native protein variants towards 1-chloro-2,4-dinitrobenzene, 4-vinylpridine and (+)-anitbenzo[a]pyrene-7,8-diol-9,10-0x9de. Cancer Letters 156, 167–175.CrossRefGoogle Scholar
Coudray, C, Bellanger, J, Castiglia-Delavaud, C, Remesy, C, Vermorel, M & Rayssiguier, Y (1997) Effect of soluble or partly soluble dietary fibres supplementation on absorption and balance of calcium, magnesium, iron and zinc in healthy young men. European Journal of Clinical Nutrition 51, 375–380.CrossRefGoogle ScholarPubMed
Cummings, JH, Pomare, EW, Branch, WJ, Naylor, CPE & Macfarlane, GT (1987) Short chain fatty acids in human large intestine, portal, hepatic and venous blood. Gut 28, 1221–1227.CrossRefGoogle ScholarPubMed
Den Hond, EM, Geypens, B & Ghoos, Y (2000) Effect of high performance chicory inulin on constipation. Nutrition Research 20, 731–736.CrossRefGoogle Scholar
Doll, R (1991) The lessons of life: Keynote address to the Nutrition and Cancer Conference. Cancer Research 52, Supplement, 2024S–2029S.Google Scholar
Doll, R (1996) Nature and nurture: possibilities for cancer control. Carcinogenesis 17, 177–184.CrossRefGoogle ScholarPubMed
Doll, R & Peto, R (1981) The causes of cancer: Quantitative estimates of avoidable risks of cancer in the United States today. Journal of the National Cancer Institute 66, 1191–1308.CrossRefGoogle ScholarPubMed
Ellgard, L, Andersson, H, Bosaeus, I & Bosaeus, I (1997) Inulin and oligofructose do not influence the absorption of cholestrol, or the excretion of cholesterol, Ca, Mg, Zn, Fe, or bile acids but increase energy excretion in ileostomy subjects. European Journal of Clinical Nutrition 45, 451–457.Google Scholar
Fearon, ER (1997) Human cancer syndromes: Clues to the origin and nature of cancer. Science 278, 1043–1050.CrossRefGoogle Scholar
Gallaher, DD & Khil, J (1999) The effect of synbiotics on colon carcinogenesis in rats. Journal of Nutrition 129, 1483S–1487S.CrossRefGoogle ScholarPubMed
Gibson, GR, Beatty, ER, Wang, X & Cummings, J (1995) Selective stimulation of bifidobacteria in the human colon by oligofructose and inulin. Gastroenterology 108, 975–982.CrossRefGoogle ScholarPubMed
Gibson, GR & Roberfroid, MB (1995) Dietary modulation of the human colonic microbiota: Introducing the concept of prebiotics. Journal of Nutrition 125, 1401–1412.CrossRefGoogle ScholarPubMed
Gibson, GR & Wang, X (1994) Regulatory effects of bifidobacteria on the growth of other colonic bacteria. Journal of Applied Bacteriology 77, 412–420.CrossRefGoogle ScholarPubMed
Hague, A, Elder, DJE, Hicks, DJ & Pareskeva, C (1995) Apoptosis in colorectal tumour cells: Induction by the short chain fatty acids butyrate, propionate and acetate and by the bile salt deoxycholate. International Journal of Cancer 60, 400–406.CrossRefGoogle ScholarPubMed
Hague, A & Paraskeva, C (1995) The short-chain fatty acid butyrate induces apoptosis in colorectal tumour cell lines. European Journal of Cancer Prevention 4, 359–364.CrossRefGoogle ScholarPubMed
Hale, AJ, Smith, CA, Sutherland, LC, Stoneman, VEA, Longthorne, VL, Culhane, AC & Williams, GT (1996) Apoptosis: molecular regulation of cell death. European Journal of Biochemistry 236, 1–26.CrossRefGoogle ScholarPubMed
Hollstein, M, Sidransky, D, Vogelstein, B & Harris, CC (1991) P53 mutations in human cancers. Science 253, 49–53.CrossRefGoogle ScholarPubMed
Hughes, R & Rowland, IR (2001) Stimulation of apoptosis by two prebiotic chicory fructans in the rat colon. Carcinogenesis 22, 43–47.CrossRefGoogle ScholarPubMed
Ishikawa, T (1992) The ATP-dependent glutathione S-conjugate export pump. TIBS 17, 463–468.Google ScholarPubMed
Johnson, IT, Williamson, G & Musk, SRR (1994) Anticarcinogenic factors in plant foods: A new class of nutrients? Nutrition Research Reviews 7, 175–204.CrossRefGoogle Scholar
Kassie, F, Pool-Zobel, BL, Parzefall, W, Schulte-Hermann, R & Knasmuller, S (1999) Investigations on the genotoxic effects of benzylisothiocyanate, a natural chemopreventive agent. Mutagenesis 14, 595–603.CrossRefGoogle ScholarPubMed
Kerr, JFR, Wyllie, AH & Currie, AR (1972) Apoptosis: a basic biological phenomenon with wide ranging implications in tissue kinetics. British Journal of Cancer 26, 239–257.CrossRefGoogle ScholarPubMed
Kirlin, WG, Cai, J, Delong, MJ, Patten, EJ & Jones, DP (1999) Dietary compounds that induce cancer preventive phase 2 enzymes activate apoptosis at comparable doses in HT29 colon carcinoma cells. Journal of Nutrition 129, 1827–1835.CrossRefGoogle ScholarPubMed
Kleessen, B, Sykura, B, Zunft, HJ & Blaut, M (1997) Effects of inulin and lactose on fecal microflora, microbial activity, and bowel habit in elderly constipated persons. American Journal of Clinical Nutrition 65, 1397–1402.CrossRefGoogle ScholarPubMed
Kroemer, G, Petit, P, Zamzami, N, Vayssiere, JL & Mignotte, B (1995) The biochemistry of programmed cell death. FASEB Journal 9, 1277–1287.CrossRefGoogle ScholarPubMed
Kruse, HP, Kleessen, B & Blaut, M (1999) Effects of inulin on faecal bifidobacteria in human subjects. British Journal of Nutrition 82, 375–382.CrossRefGoogle ScholarPubMed
Ling, WH, Korpela, R, Mykkanen, H, Salminen, S & Hanninen, O (1994) Lactobacillus strain Gg supplementation decreases colonic hydrolytic and reductive enzyme activities in healthy female adults. Journal of Nutrition 124, 18–23.CrossRefGoogle ScholarPubMed
Lupton, JR (1995) Butyrate and colonic cytokinetics: differences between in vitro and in vivo studies. European Journal of Cancer Prevention 4, 373–378.CrossRefGoogle ScholarPubMed
Magnuson, B, Carr, I & Bird, RP (1993) Ability of aberrant crypt foci characteristics to predict colonic tumor incidence in rats fed cholic acid. Cancer Research 53, 4499–4504.Google ScholarPubMed
McIntyre, A, Gibson, PR & Young, GP (1993) Butyrate production from dietary fibre and protection against large bowel cancer in a rat model. Gut 34, 386–391.CrossRefGoogle ScholarPubMed
Morra, G & Boland, CR (1995) Heriditary nonpolyposis colorectal cancer: the syndrome, the genes and historical perspectives. Journal of the National Cancer Institute 87, 1114–1125.CrossRefGoogle Scholar
Moshfegh, AJ, Friday, JE, Goldman, JP & Chug-Ahuja, JK (1999) Presence of inulin and oligofructose in the diets of Americans. British Journal of Nutrition 129, 1407S–1411S.CrossRefGoogle ScholarPubMed
Mutanen, M, Pajari, AM & Oikarinen, SI (2000) Beef induces and rye bran prevents the formation of intestinal polyps in ApcMin mice: relation to β-catenin and PKC isozymes. Carcinogenesis 21, 1167–1173.CrossRefGoogle ScholarPubMed
Nijhoff, WA, Mulder, TPJ, Verhagen, H, Van Poppel, G & Peters, WHM (1995) Effects of consumption of Brussels sprouts on plasma and urinary glutathione S-transferase class-α and -π in humans. Carcinogenesis 16, 955–957.CrossRefGoogle ScholarPubMed
Osswald, K, Becker, TW, Grimm, M, Jahreis, G & Pool-Zobel, BL (2000) Inter-and Intra-individual variation of faecal water – genotoxicity in human colon cells. Mutation Reserch 472, 59–70.CrossRefGoogle ScholarPubMed
Pereira, MA, Barnes, LH, Rassman, VL, Kelloff, GV & Steele, VE (1994) Use of azoxymethane-induced foci of aberrant crypts in rat colon to identify potential cancer chemopreventive agents. Carcinogenesis 15, 1049–1054.CrossRefGoogle ScholarPubMed
Perrin, P, Pierre, F, Patry, Y, Champ, M, Berreur, M, Pradal, G, Bornet, P, Meflah, K & Menenteau, J (2001) Only fibres promoting a stable butyrate producing colonic ecosystem decrease the rate of aberrant crypt foci in rats. Gut 48, 53–61.CrossRefGoogle ScholarPubMed
Peters, WHM, Roelofs, HMJ, Nagengast, FM & Van Tongeren, JHM (1989) Human intestinal glutathione S-transferases. Biochem Journal 257, 471–476.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 Research 57, 225–228.Google ScholarPubMed
Pool-Zobel, BL, Abrahamse, SL, Collins, AR, Kark, W, Gugler, R, Oberreuther, D, Siegel, EG, Tretow-Van Lishaut, S & Rechkemmer, G (1999) Analysis of DNA strand breaks, oxidized bases and glutathione S-transferase P1 in human colon cells. Cancer Epidemiology Biomedical Preview 8, 609–614.Google ScholarPubMed
Pool-Zobel, BL, Abrahamse, SL & Rechkemmer, G (1995) Pretreatment of colon cells with sodium butyrate but not iso-butyrate protects them from DNA damage induced by hydrogen peroxide. Proceedings, (Abstract).Google Scholar
Pool-Zobel, BL & Leucht, U (1997) Induction of DNA damage in human colon cells derived from biopsies by suggested risk factors of colon cancer. Mutation Research 375, 105–116.CrossRefGoogle Scholar
Pool-Zobel, BL, Neudecker, C, Domizlaff, I, Ji, S, Schillinger, U, Rumney, CJ, Moretti, M, Villarini, M, Scassellati-Sforzolini, G & Rowland, IR (1996) Lactobacillus-and Bifidobacterium-mediated antigenotoxicity in colon cells of rats: Prevention of carcinogen-induced damage in vivo and elucidation of involved mechanisms. Nutrition Cancer 26, 365–380.CrossRefGoogle Scholar
Reddy, BS (1998) Prevention of colon cancer by pre and probiotics: evidence from laboratory studies. British Journal of Nutrition 80, S219–S223.CrossRefGoogle ScholarPubMed
Reddy, BS, Hamid, R & Rao, CV (1997) Effect of dietary oligofructose and inulin on colonic preneoplastic aberrant crypt foci inhibition. Carcinogenesis 18, 1371–1374.CrossRefGoogle ScholarPubMed
Rehman, A, Collis, CS, Yang, M, Kelly, M, Diplock, AT, Halliwell, B & Rice-Evans, CA (1998) The effects of iron and vitamin C co-supplementation on oxidative dmage to DNA in healthy volunteers. Biochemistry Biophysiology Research Commun 246, 293–298.CrossRefGoogle Scholar
Roberfroid, MB, Van Loo, J & Gibson, GR (1998) The Bifidogenic nature of chicory inulin and its hydrolysis products. Journal of Nutrition 128, 11–19.CrossRefGoogle ScholarPubMed
Roediger, WEW (1989) The utilisation of nutrients by isolated epithelial cells of the rat colon. Gastroenterology 83, 424–429.CrossRefGoogle Scholar
Roland, N, Migpm-Baudon, L, Flinois, JP & Beaune, PH (1994) Hepatic and Intestinal cytochrome P450, Glutathone s-transferase and UDP Glucuronosyl transferase are affected by six types of dietary fiber in rats inoculated with human whole fecal flora. Journal of Nutrition 124, 1581–1587.CrossRefGoogle Scholar
Roland, N, Rabot, B & Nugon-Baudon, L (1996) Modulation of the biological effects of glucosinolates by inulin and oat fibre in gnotobiotic rats inoculated with a human whole faecal flora. Food and Chemical Toxicology 34, 671–677.CrossRefGoogle ScholarPubMed
Rowland, IR (1991) Nutrition and gut flora metabolism. In Nutrition, Toxicity and Cancer, pp. 113–136 [Rowland, IR, editor]. Boca Raton, FL: CRC Press.Google Scholar
Rowland, IR, Rumney, CJ, Coutts, JT & Lievense, LC (1998) Effect of Bifidobacterium longum and inulin on gut bacterial metabolism and carcinogen-induced aberrant crypt foci in rats. Carcinogenesis 19, 281–285.CrossRefGoogle ScholarPubMed
Saavedra, JM, Tscherina, A, Moore, N, Abi-Hanna, A, Coletta, F, Emenhiser, C & Yolken, RH (1999) Gastro-ntestinal function in infants consumin a weaning food supplemented with oligo-fructose, a prebiotic. Journal of Paediatrics, Gastroenterology and Nutrition 29, A95.Google Scholar
Schneemann, BO (1999) Fiber, inulin and oligofructose: similarities and differences. British Journal of Nutrition 129, 1424S–1427S.CrossRefGoogle Scholar
Sesink, ALA, Termont, DSML, Kleibeuker, JH & Van der Meer, R (2000) Red meat and colon cancer: dietary heme, but not fat, has cytotoxic and hyperproliferative effects on rat colonic epithelium. Carcinogenesis 21, 1909–1915.CrossRefGoogle Scholar
Singh, J, Rivenson, A, Tomita, M, Shimamura, S, Ishibashi, N & Reddy, BS (1997) Bifidobacterium longum, a lactic acid-producing intestinal microflora inhibit colon cancer and modulate the intermediate biomarkers of colon carcinogenesis. Carcinogenesis 18, 1371–1377.CrossRefGoogle Scholar
Stein, J, Schroder, O, Bonk, M, Oremek, G, Lorenz, M & Caspary, WF (1996) Induction of glutathione-S-transferase-pi by short-chain fatty acids in the intestinal cell line Caco-2. European Journal of Clinical Investigation 26, 84–87.CrossRefGoogle ScholarPubMed
Steller, H (1995) Mechanisms and genes of cellular suicide. Science 267, 1445–1449.CrossRefGoogle ScholarPubMed
Thompson, CB (1995) Apoptosis in the pathogenesis and treatment of disease. Science 267, 1456–1462.CrossRefGoogle ScholarPubMed
Treptow-van Lishaut, S, Rechkemmer, G, Rowland, IR, Dolara, P & Pool-Zobel, BL (1999) The carbohydrate crystalean and colonic microflora modulate expression of glutathione S-transferase subunits in colon of rats. European Journal of Nutrition 38, 76–83.CrossRefGoogle ScholarPubMed
Turesky, RJ, Lang, NP, Butler, MA, Teitel, CH & Kadlubar, FF (1991) Metabolic activation of carcinogenic heterocyclic aromatic amines by human liver and colon. Carcinogenesis 12, 1839–1845.CrossRefGoogle ScholarPubMed
Van den Heufel, E, Muys, T, Van Dokkum, W & Schaafsma, G (1999) Oligofructose stimulates calcium absorption in adolescents. American Journal of Clinical Nutrition 35, 525–552.Google Scholar
Van Lieshout, EMM, Peters, WHM & Jansen, JB (1996) Effect of oltipraz, alpha-tocopherol, betacarotene and phenethylisothiocyanate on rat oesopageal, gastric, colonic and heptatic glutathone, glutathione S-transferase and peroxidase. Carcinogenesis 17, 1439–1445.CrossRefGoogle Scholar
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. Crititcal Reviews of Food Science Nutrition 35, 525–552.CrossRefGoogle ScholarPubMed
Van Loo, J, Cummings, JH, Delzenne, N, Englyst, HN, Franck, A, Hopkins, MJ, Kok, N, Macfarlane, GT, Newton, DF, Quigley, ME, Roberfroid, MR, van Vliet, T & Van den Heuvel, EGH (1999) Functional food properties of non digestible oligosaccharides: a consensus report from the ENDO project (DGXII AIRII-CT94-1095). British Journal of Nutrition 81, 121–132.Google ScholarPubMed
Van Loo, J & Jonkers, N (2001) Evaluation in human volunteers of the potential anticarcinogenic activities of novel nutritional concepts prebiotics, probiotics and synbiotics (the SYNCAN project QLK1-1999-00346). Nutrition Metabolism Cardiovascular Disease 11, Suppl to No 4, 87–93.Google ScholarPubMed
Van Munster, IP, Tangerman, A & Nagengast, FM (1994) Effect of resistant starch on colonic fermentation, bile acid metabolism, and mucosal proliferation. Digestive Diseases and Sciences 39, 834–842.CrossRefGoogle ScholarPubMed
Verghese, M, Rao, DR, Chawan, CB & Schackelford, LA (2002 a) Dietary inulin suppresses azoxymethane-induced preneoplastic aberrant crypt foci in mature Fisher-344 rats. Journal of Nutrition (in press).Google ScholarPubMed
Verghese, M, Rao, DR, Williams, LL & Schackelford, LA (2002 b) Dietary inulin suppresses azoxymethane-induced aberrant crypt foci and colon tumors at the promotion stage in Fisher-344 rats. Journal of Nutrition (in press).Google ScholarPubMed
Wargovich, MJ, Harris, C, Chen, CD, Palmer, C, Steele, VE & Kelloff, G (1992) Growth kinetics and chemoprevention of aberrant crypts in the rat colon. Journal of Cellular Biochemistry 15G, Supplement, 51–54.CrossRefGoogle Scholar
Wattenberg, LW (1992) Inhibition of carcinogenesis by minor dietary constituents. Cancer Research 52, Suppl., 2085S–2091S.Google ScholarPubMed
Williams, CM (1999) Effects of inulin on lipid parameters in humans. British Journal of Nutrition 129, 1471S–1473S.CrossRefGoogle ScholarPubMed
Wollowski, I, Ji, S, Bakalinsky, AT, Neudecker, C & Pool-Zobel, BL (1999) Bacteria used for the production of yogurt inactivate carcinogens and prevent DNA damage in the colon of rats. Journal of Nutrition 129, 77–82.CrossRefGoogle ScholarPubMed