Hostname: page-component-78c5997874-8bhkd Total loading time: 0 Render date: 2024-11-13T14:36:34.197Z Has data issue: false hasContentIssue false
  • English
  • Français

Butyrate is only one of several growth inhibitors produced during gut flora-mediated fermentation of dietary fibre sources

Published online by Cambridge University Press:  09 March 2007

Gabriele Beyer-Sehlmeyer ,
Michael Glei ,
Esther Hartmann ,
Rosin Hughes ,
Christoph Persin ,
Volker Böhm ,
Rainer Schubert ,
Gerhard Jahreis  and
Beatrice L. Pool-Zobel
Gabriele Beyer-Sehlmeyer
Affiliation:
Department of Nutritional Toxicology, Institute for Nutrition, Friedrich Schiller University, Dornburger Str. 25, D-07743 Jena, Germany
Michael Glei
Affiliation:
Department of Nutritional Toxicology, Institute for Nutrition, Friedrich Schiller University, Dornburger Str. 25, D-07743 Jena, Germany
Esther Hartmann
Affiliation:
Department of Nutritional Toxicology, Institute for Nutrition, Friedrich Schiller University, Dornburger Str. 25, D-07743 Jena, Germany
Rosin Hughes
Affiliation:
Northern Ireland Centre for Diet and Health (NICHE), School of Biomedical Sciences, University of Ulster, Coleraine BT52 1SA, UK
Christoph Persin
Affiliation:
Kampffmeyer Food Service GmbH, Trettaustr. 32-34, 21107 Hamburg, Germany
Volker Böhm
Affiliation:
Department of Human Nutrition, Institute for Nutrition, Friedrich Schiller University, Dornburger Str. 29, D-07743 Jena, Germany
Rainer Schubert
Affiliation:
Department of Nutritional Physiology, Institute for Nutrition, Friedrich Schiller University, Dornburger Str. 25, D-07743 Jena, Germany
Gerhard Jahreis
Affiliation:
Department of Nutritional Physiology, Institute for Nutrition, Friedrich Schiller University, Dornburger Str. 25, D-07743 Jena, Germany
Beatrice L. Pool-Zobel*
Affiliation:
Department of Nutritional Toxicology, Institute for Nutrition, Friedrich Schiller University, Dornburger Str. 25, D-07743 Jena, Germany
*
*Corresponding author: Professor Beatrice L. Pool-Zobel, fax +49 36 41 94 96 72, email b8pobe@uni-jena.de
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

Dietary fibre sources are fermented by the gut flora to yield short-chain fatty acids (SCFA) together with degraded phytochemicals and plant nutrients. Butyrate, a major SCFA, is potentially chemoprotective by suppressing the growth of tumour cells and enhancing their differentiation. Conversely, it could lead to a positive selection pressure for transformed cells by inducing glutathione S-transferases (GST) and enhancing chemoresistance. Virtually nothing is known about how butyrate's activities are affected by other fermentation products. To investigate such interactions, a variety of dietary fibre sources was fermented with human faecal slurries in vitro, analysed for SCFA, and corresponding SCFA mixtures were prepared. HT29 colon tumour cells were treated for 72 h with individual SCFA or complex samples. The growth of cells, GST activity, and chemoresistance towards 4-hydroxynonenal were determined. Fermentation products inhibited cell growth more than the corresponding SCFA mixtures, and the SCFA mixtures were more active than butyrate, probably due to phytoprotectants and to propionate, respectively, which also inhibit cell growth. Only butyrate induced GST, whereas chemoresistance was caused by selected SCFA mixtures, but not by all corresponding fermentation samples. In summary, fermentation supernatant fractions contain compounds that: (1) enhance the anti-proliferative properties of butyrate (propionate, phytochemical fraction); (2) do not alter its capacity to induce GST; (3) prevent chemoresistance in tumour cells. It can be concluded that fermented dietary fibre sources are more potent inhibitors of tumour cell growth than butyrate alone, and also contain ingredients which counteract the undesired positive selection pressures that higher concentrations of butyrate induce in tumour cells.

Keywords

Short-chain fatty acidsComplex gut fermentation productsGenotoxicity4-Hydroxynonenal
Type
Research Article
Information
British Journal of Nutrition , Volume 90 , Issue 6 , December 2003 , pp. 1057 - 1070
Copyright
Copyright © The Nutrition Society 2003

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
Alberts, DS, Martinez, ME, Roe, DJ, et al. . (2000) Lack of effect of a high-fiber cereal supplement on the recurrence of colorectal adenomas. Phoenix Colon Cancer Prevention Physicians’ Network. N Engl J Med 342, 1156–1162.10.1056/NEJM200004203421602CrossRefGoogle ScholarPubMed
Anonymous (1990) Oilseeds. Determination of glucosinolates by high-performance liquid chromatography. Off J Eur Commun L170, 27–34.Google Scholar
Association of Official Analytical Chemists International (1992) Total Dietary Fiber, Official Methods of Analysis 15th ed. Gaithersburg, MD: Association of Official Analytical Chemists International.Google Scholar
Augeron, C & Laboisse, CL (1984) Emergence of permanently differentiated cell clones in a human colonic cancer cell line in culture after treatment with sodium butyrate. Cancer Res 44, 3961–3969.Google Scholar
Baghurst, PA, Baghurst, KI & Record, SJ (1996) Dietary fibre, non-starch polysaccharides and resistant starch: a review. Food Aust 48, Suppl. S3–S35.Google Scholar
Barry, JL, Hoebler, C, Macfarlane, GT, et al. . (1995) Estimation of the fermentability of dietary fibre in vitro: a European interlaboratory study. Br J Nutr 74, 303–322.10.1079/BJN19950137CrossRefGoogle ScholarPubMed
Berhane, K, Widersten, M, Engstrom, A, Kozarich, JW & Mannervik, B (1994) Detoxication of base propenals and other α,β-unsaturated aldehyde products of radical reactions and lipid peroxidation by humane glutathione transferases. Proc Natl Acad Sci USA 91, 1480–1484.CrossRefGoogle Scholar
Bingham, SA, Day, NE, Luen, R, et al. . (2003) Dietary fibre in food and protection against colorectal cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC): an observational study. Lancet 361, 1496–1501.10.1016/S0140-6736(03)13174-1CrossRefGoogle ScholarPubMed
Board, P (1998) Identification of cDNAs encoding two human alpha class glutathione transferases (GSTA3 and GSTA4) and the heterologous expression of GSTA4-4. Biochem J 330, 827–831.CrossRefGoogle ScholarPubMed
Böhm, V (1999) Effect of subambient temperature on RP-HPLC of carotene isomers. Chromatographia 50, 282–286.10.1007/BF02490829CrossRefGoogle Scholar
Bowers, GN & McComb, RB (1966) A continuous spectrophotometric method for measuring the activity of serum alkaline phosphatase. Clin Chem 12, 70–89.10.1093/clinchem/12.2.70CrossRefGoogle ScholarPubMed
Bradford, MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72, 248–254.CrossRefGoogle ScholarPubMed
Briviba, K, Abrahamse, SL, Pool-Zobel, BL & Rechkemmer, G (2001a) Neurotensin- and EGF-induced metabolic activation of colon carcinoma cells is diminished by dietary flavonoid cyanidin but not by its glycosides. Nutr Cancer 41, 172–179.10.1080/01635581.2001.9680629CrossRefGoogle Scholar
Briviba, K, Schnabele, K, Schwertle, E, Blockhaus, M & Rechkemmer, G (2001b) β-Carotene inhibits growth of human colon carcinoma cells in vitro by induction of apoptosis. Biol Chem 382, 1663–1668.10.1515/BC.2001.201CrossRefGoogle ScholarPubMed
Bruns, CM, Hubatsch, I, Ridderström, M, Mannervik, B & Tainer, JA (1999) Human glutathione transferase A4-4 crystal structures and mutagenesis reveal the basis of high catalytic efficiency of the toxic lipid peroxidation products. J Mol Biol 288, 427–439.CrossRefGoogle ScholarPubMed
Burkitt, DS (1969) Related disease-related cause?. Lancet 2, 1229–1231.CrossRefGoogle ScholarPubMed
Compher, CW, Frankel, WL, Tazelaar, J, et al. . (1999) Wheat bran decreases aberrant crypt foci, preserves normal proliferation, and increases intraluminal butyrate levels in experimental colon cancer. J Parenter Enteral Nutr 23, 269–277.CrossRefGoogle ScholarPubMed
Cummings, J (1981) Short-chain fatty acids in the human colon. Gut 22, 763–779.10.1136/gut.22.9.763CrossRefGoogle 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
Day, AJ, Bao, Y, Morgan, MRA & Williamson, G (2000) Conjugation position of quercetin glucuronides and effect on biological activity. Free Radic Biol Med 29, 1234–1243.CrossRefGoogle ScholarPubMed
Duthie, SJ, Johnson, W & Dobson, VL (1997) The effect of dietary flavonoids on DNA damage (strand breaks and oxidised pyrimidines) and growth in human cells. Mutat Res 390, 141–151.CrossRefGoogle ScholarPubMed
Ebert, MN, Beyer-Sehlmeyer, G, Liegibel, UM, Kautenburger, T, Becker, TW & Pool-Zobel, BL (2001) Butyrate-induced activation of glutathione S-transferases protects human colon cells from genetic damage by 4-hydroxynonenal. Nutr Cancer 41, 156–164.10.1080/01635581.2001.9680627CrossRefGoogle Scholar
Ferguson, LR, Chavan, RR & Harris, PJ (2001) Changing concepts of dietary fiber: implications for carcinogenesis. Nutr Cancer 39, 155–169.10.1207/S15327914nc392_1CrossRefGoogle ScholarPubMed
Ferguson, LR & Harris, PJ (2003) The dietary fibre debate: more food for thought - commentary. Lancet 361, 1487–1488.CrossRefGoogle Scholar
Fuchs, CS, Giovannucci, E, Colditz, GA, et al. . (1999) Dietary fiber and the risk of colorectal cancer and adenoma in women. N Engl J Med 340, 169–176.CrossRefGoogle ScholarPubMed
Gamet, L, Daviaud, D, Denis-Pouxviel, C, Remesy, C & Murat, J-C (1992) Effects of short-chain fatty acids on growth and differentiation of the human colon cancer cell line HT29. Int J Cancer 52, 286–289.CrossRefGoogle ScholarPubMed
Gibson, PR, Rosella, O, Wilson, AJ, et al. . (1999) Colonic epithelial cell activation and the paradoxical effects of butyrate. Carcinogenesis 20, 539–544.CrossRefGoogle ScholarPubMed
Glei, M, Liegibel, UM, Ebert, MN, Böhm, V & Pool-Zobel, BL (2002) beta-Carotene reduces bleomycin-induced genetic damage in human lymphocytes. Toxicol Appl Pharmacol 179, 65–73.10.1006/taap.2001.9329CrossRefGoogle ScholarPubMed
Glei, M, Matuschek, M, Steiner, C, Böhm, V, Persin, C & Pool-Zobel, BL (2003) Initial in vitro toxicity testing of functional foods rich in catechins and anthocyanins in human cells. Toxicol In Vitro (In the Press).CrossRefGoogle Scholar
Habig, WH, Pabst, MJ & Jakoby, WB (1974) Glutathione S-transferase. The first enzymatic step in mercapturic acid formation. J Biol Chem 249, 7130–7139.CrossRefGoogle Scholar
Hague, A, Manning, AM, Hanlon, KA, Huschtscha, LI, Hart, D & Paraskeva, C (1993) Sodium butyrate induces apoptosis in human colonic tumour cell lines in a p53-independent pathway: implications for the possible role of dietary fibre in the prevention of large-bowel cancer. Int J Cancer 55, 505.CrossRefGoogle Scholar
Hague, A & Paraskeva, C (1995) The short-chain fatty acid butyrate induces apoptosis in colorectal tumour cell lines. Eur J Cancer Prev 4, 359–364.CrossRefGoogle ScholarPubMed
Harris, PJ & Ferguson, LR (1993) Dietary fibre: its composition and role in protection against colorectal cancer. Mutat Res 290, 97–110.CrossRefGoogle ScholarPubMed
Hill, MJ (1995) Introduction: dietary fibre, butyrate and colorectal cancer. Eur J Cancer Prev 4, 341–343.CrossRefGoogle ScholarPubMed
Johnson, IT, Williamson, G & Musk, SRR (1994) Anticarcinogenic factors in plant foods: a new class of nutrients? Nutr Res Rev 7, 175–204.CrossRefGoogle Scholar
Kestell, P, Zhao, L, Zhu, S, Harris, PJ & Ferguson, LR (1999) Studies on the mechanism of cancer protection by wheat bran: effects on the absorption, metabolism and excretion of the food carcinogen 2-amino-3-methylimidazo[4,5-f]quinoline (IQ). Carcinogenesis 20, 2253–2260.CrossRefGoogle Scholar
Kiessling, G, Schneider, J & Jahreis, G (2002) Long-term consumption of fermented dairy products over 6 months increases HDL cholesterol. Eur J Clin Nutr 56, 1–7.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. J Nutr 129, 1827–1835.10.1093/jn/129.10.1827CrossRefGoogle ScholarPubMed
Kobayashi, H & Fleming, SE (2001) The source of dietary fiber influences - short chain fatty acid production and concentrations in the large bowel. In CRC Handbook of Dietary Fiber in Human Nutrition, pp. 287–315 [Spiller, GA, editor]. Boca Raton, FL: CRC Press.Google Scholar
Kruh, J (1982) Effects of sodium butyrate, a new pharmacological agent, on cells in culture. Mol Cell Biochem 42, 65–82.Google ScholarPubMed
Lupton, JR (1995) Butyrate and colonic cytokinetics: differences between in vitro and in vivo studies. Eur J Cancer Prev 4, 373–378.CrossRefGoogle ScholarPubMed
McIntosh, GH, Royle, PJ & Pointing, G (2001) Wheat aleurone flour increases cecal beta-glucuronidase activity and butyrate concentration and reduce colon adenoma burden in azoxymethane-treated rats. J Nutr 131, 127–131.CrossRefGoogle 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
McKeown-Eyssen, GE, Bight-See, E, Bruce, WR, et al. . (1994) A randomized trial of a low fat high fibre diet in the recurrence of colorectal polyps. Toronto Polyp Prevention Group. J Clin Epidemiol 47, 525–536.CrossRefGoogle ScholarPubMed
Mariadason, JM, Velchich, A, Wilson, AJ, Augenlicht, LH & Gibson, PR (2001) Resistance to butyrate-induced cell differentiation and apoptosis during spontaneous Caco-2 cell differentiation. Gastroenterology 120, 889–899.CrossRefGoogle ScholarPubMed
Matuschek, M, Glei, M & Pool-Zobel, BL (2001) Effect of anthocyanins on DNA-damage in HT29 clone 19 A cells. In Vitamine und Zusatzstoffe in der Ernährung von Mensch und Tier 8, pp. 345–348 [Schubert, R, Flachowsky, G, Jahreis, G and Bitsch, R, editors]. Braunschweig: Bundesforschungsanstalt für Landwirtschaft (FAL).Google Scholar
Miyanishi, K, Takayama, T & Ohi, M (2001) Glutathione S-transferase pi overexpression is closely associated with K-ras mutation during human colon carcinogenesis. Gastroenterology 121, 865–874.CrossRefGoogle ScholarPubMed
Parkin, MD, Stjernsward, J & Muir, C (1988) Estimates of the worldwide frequency of twelve major cancers. Int J Cancer 41, 184–197.CrossRefGoogle Scholar
Perrin, P, Pierre, F, Patry, Y, et al. . (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, U, Sinha, R, Chaterjee, N, et al. . (2003) Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial Project Team Dietary fibre and colorectal adenoma in a colorectal cancer early detection programme. Lancet 361, 1491–1495.CrossRefGoogle Scholar
Peters, WHM, Boon, CEW, Roelofs, HMJ & Wobbes, T (1992) Expression of drug-metabolizing enzymes and P-170 glycoprotein in colorectal carcinoma and normal mucosa. Gastroenterology 103, 448–455.10.1016/0016-5085(92)90833-KCrossRefGoogle ScholarPubMed
Pietinen, P, Malila, N, Virtanen, M, et al. . (1999) Diet and risk of colorectal cancer in a cohort of Finnish men. Cancer Causes Control 10, 387–396.CrossRefGoogle Scholar
Pool-Zobel, BL, Abrahamse, SL & Rechkemmer, G (1996) Pretreatment of colon cells with sodium butyrate but not iso-butyrate protects them from DNA damage induced by hydrogen peroxide. In Dietary Phytochemicals in Cancer Prevention and Treatment, pp. 287 [American Institute for Cancer Research, editor]. New York and London: Plenum Press.Google Scholar
Pool-Zobel, BL, Adlercreutz, H & Glei, M (2000) Isoflavonoids and lignans have different potentials to modulate oxidative genetic damage in human colon cells. Carcinogenesis 21, 1247–1252.CrossRefGoogle ScholarPubMed
Pool-Zobel, BL, Bub, A, Liegibel, UM, Treptow-Van Lishaut, S & Rechkemmer, G (1998) Mechanisms by which vegetable consumption reduces genetic damage in humans. Canc Epid Biom Prev 7, 891–899.Google ScholarPubMed
Pool-Zobel, BL, Bub, A, Schröder, N & Rechkemmer, G (1999) Anthocyanins are potent antioxidants in vitro but do not reduce oxidative DNA damage within human colon cells. Eur J Nutr 38, 227–234.CrossRefGoogle Scholar
Roediger, WEW (1989) The utilisation of nutrients by isolated epithelial cells of the rat colon. Gastroenterology 83, 424–429.CrossRefGoogle Scholar
Rosignoli, P, Fabiani, R & De Bartolomeo, A (2001) Protective activity of butyrate on hydrogen peroxide-induced DNA damage in isolated human colonocytes and HT29 tumour cells. Carcinogenesis 22, 1675–1680.CrossRefGoogle ScholarPubMed
Ryden, P & Robertson, JA (1995) The consequences of fruit and vegetable fibre fermentation on their binding capacity for MeIQx and the effects of soluble fibre sources on the binding affinity of wheat bran preparations. Carcinogenesis 16, 1711–1716.CrossRefGoogle ScholarPubMed
Schäferhenrich, A, Beyer-Sehlmeyer, G, Festag, G, et al. . (2003a) Human adenoma cells are highly susceptible to the genotoxic action of 4-hydroxy-2-nonenal. Mutat Res 526, 19–32.CrossRefGoogle Scholar
Schäferhenrich, A, Sendt, W, Scheele, J, et al. . (2003b) Putative colon cancer risk factors damage global DNA and TP53 in primary human colon cells isolated from surgical samples. Food Chem Toxicol 41, 655–664.CrossRefGoogle Scholar
Schatzkin, A, Friedman, LS, Lanza, E & Tungrea, J (1995) Diet and colorectal cancer: still an open question. J Natl Cancer Inst 87, 1733–1735.CrossRefGoogle ScholarPubMed
Schatzkin, A, Lanza, E, Corle, D, et al. . (2000) Lack of effect of a low-fat, high-fiber diet on the recurrence of colorectal adenomas. Polyp Prevention Trial Study Group. N Engl J Med 342, 1149–1155.CrossRefGoogle ScholarPubMed
Schlesier, K, Harwat, M, Böhm, V & Bitsch, R (2002) Assessment of antioxidant activity by using different in vitro methods. Free Rad Res 36, 177–187.CrossRefGoogle ScholarPubMed
Silvester, KR, Bingham, SA, Pollock, JRA, Cummings, J & O'Neill, I (1998) Effect of meat and resistant starch on fecal excretion of apparent N-nitroso compounds and ammonia from the human large bowel. Nutr Cancer 29, 13–23.10.1080/01635589709514596CrossRefGoogle Scholar
Singh, NP, McCoy, MT, Tice, RR & Schneider, EL (1988) A simple technique for quantitation of low levels of DNA damage in individual cells. Exp Cell Res 175, 184–191.10.1016/0014-4827(88)90265-0CrossRefGoogle 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. Eur J Nutr 38, 76–83.CrossRefGoogle ScholarPubMed
Van Soest, PJ, Robinson, JB & Lewis, BA (1991) Methods for dietary fiber, neutral detergent fiber, and nonstarch polysaccharides in relation to animal nutrition. J Dairy Sci 74, 3583–3589.CrossRefGoogle ScholarPubMed
Vosseler, C (2000) Modulation der DNA-Reparatur in HT29 clone 19A-Zellen durch β-Carotin. Diploma thesis, Friedrich Schiller University, Jena, Germany.Google Scholar
Wang, X & Gibson, GR (1993) Effects of the in vitro fermentation of oligofructose and inulin by bacteria growing in the human large intestine. J Appl Bacteriol 75, 373–380.CrossRefGoogle ScholarPubMed
Wattenberg, LW (1992) Inhibition of carcinogenesis by minor dietary constituents. Cancer Res 52, Suppl. 2085s–2091s.Google ScholarPubMed
World Cancer Research Fund and American Institute for Cancer Research (1997) Food, Nutrition and the Prevention of Cancer: A Global Perspective. Washington, DC: American Institute for Cancer Research.Google Scholar