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Simulated colon fiber metabolome regulates genes involved in cell cycle, apoptosis, and energy metabolism in human colon cancer cells

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Abstract

High level of dietary fiber has been epidemiologically linked to protection against the risk for developing colon cancer. The mechanisms of this protection are not clear. Fermentation of dietary fiber in the colon results in production of for example butyrate that has drawn attention as a chemopreventive agent. Polydextrose, a soluble fiber that is only partially fermented in colon, was fermented in an in vitro colon simulator, in which the conditions mimic the human proximal, ascending, transverse, and distal colon in sequence. The subsequent fermentation metabolomes were applied on colon cancer cells, and the gene expression changes studied. Polydextrose fermentation down-regulated gene ontology classes linked with cell cycle, and affected number of metabolically active cells. Furthermore, up-regulated effects on classes linked with apoptosis, with increased caspase 2 and 3 activity, implicate that polydextrose fermentation plays a role in induction of apoptosis in colon cancer cells. The up-regulated genes involved also key regulators of lipid metabolism, such as PPARα and PGC-1α. These results offer hypotheses for the mechanisms of two health benefits linked with consumption of dietary fiber, reducing risk of development of colon cancer, and dyslipidemia.

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References

  1. Labianca R, Beretta GD, Kildani B, Milesi L, Merlin F, Mosconi S, Pessi MA, Prochilo T, Quadri A, Gatta G, de Braud F, Wils J (2010) Colon cancer. Crit Rev Oncol Hematol 74(2):106–133

    Article  PubMed  Google Scholar 

  2. McGarr SE, Ridlon JM, Hylemon PB (2005) Diet, anaerobic bacterial metabolism, and colon cancer: a review of the literature. J Clin Gastroenterol 39(2):98–109

    PubMed  Google Scholar 

  3. Hamer HM, Jonkers D, Venema K, Vanhoutvin S, Troost FJ, Brummer RJ (2008) Review article: the role of butyrate on colonic function. Aliment Pharmacol Ther 27(2):104–119. doi:10.1111/j.1365-2036.2007.03562.x

    Article  PubMed  CAS  Google Scholar 

  4. Rose DJ, DeMeo MT, Keshavarzian A, Hamaker BR (2007) Influence of dietary fiber on inflammatory bowel disease and colon cancer: importance of fermentation pattern. Nutr Rev 65(2):51–62

    Article  PubMed  Google Scholar 

  5. Scharlau D, Borowicki A, Habermann N, Hofmann T, Klenow S, Miene C, Munjal U, Stein K, Glei M (2009) Mechanisms of primary cancer prevention by butyrate and other products formed during gut flora-mediated fermentation of dietary fibre. Mutat Res 682(1):39–53

    Article  PubMed  CAS  Google Scholar 

  6. Dongowski G (2007) Interactions between dietary fibre-rich preparations and glycoconjugated bile acids in vitro. Food Chem 104(1):390–397. doi:10.1016/j.foodchem.2006.11.053

    Article  CAS  Google Scholar 

  7. Zacherl C, Eisner P, Engel K-H (2011) In vitro model to correlate viscosity and bile acid-binding capacity of digested water-soluble and insoluble dietary fibres. Food Chem 126(2):423–428. doi:10.1016/j.foodchem.2010.10.113

    Article  CAS  Google Scholar 

  8. van Bennekum AM, Nguyen DV, Schulthess G, Hauser H, Phillips MC (2005) Mechanisms of cholesterol-lowering effects of dietary insoluble fibres: relationships with intestinal and hepatic cholesterol parameters. Br J Nutr 94(3):331–337. doi:10.1079/bjn20051498

    Article  PubMed  Google Scholar 

  9. Jenkins DJ, Kendall CW, Axelsen M, Augustin LS, Vuksan V (2000) Viscous and nonviscous fibres, nonabsorbable and low glycaemic index carbohydrates, blood lipids and coronary heart disease. Curr Opin Lipidol 11(1):49–56

    Article  PubMed  CAS  Google Scholar 

  10. Drozdowski LA, Reimer RA, Temelli F, Bell RC, Vasanthan T, Thomson ABR (2010) [beta]-Glucan extracts inhibit the in vitro intestinal uptake of long-chain fatty acids and cholesterol and down-regulate genes involved in lipogenesis and lipid transport in rats. J Nutr Biochem 21(8):695–701. doi:10.1016/j.jnutbio.2009.04.003

    Article  PubMed  CAS  Google Scholar 

  11. Schauber J, Weiler F, Gostner A, Melcher R, Kudlich T, Lhrs H, Scheppach W (2006) Human rectal mucosal gene expression after consumption of digestible and non-digestible carbohydrates. Mol Nutr Food Res 50(11):1006–1012

    Article  PubMed  CAS  Google Scholar 

  12. Vanhoutvin SA, Troost FJ, Hamer HM, Lindsey PJ, Koek GH, Jonkers DM, Kodde A, Venema K, Brummer RJ (2009) Butyrate-induced transcriptional changes in human colonic mucosa. PLoS ONE 4(8):e6759

    Article  PubMed  Google Scholar 

  13. van Baarlen P, Troost F, van der Meer C, Hooiveld G, Boekschoten M, Brummer RJ, Kleerebezem M (2010) Microbes and health sackler colloquium: human mucosal in vivo transcriptome responses to three lactobacilli indicate how probiotics may modulate human cellular pathways. Proc Natl Acad Sci USA. doi:10.1073/pnas.1000079107

  14. Bing W, Bobe G, Lapres JJ, Bourquin LD (2009) Dietary carbohydrate source alters gene expression profile of intestinal epithelium in mice. Nutr Cancer 61(1):146–155

    Article  Google Scholar 

  15. Daly K, Shirazi-Beechey SP (2006) Microarray analysis of butyrate regulated genes in colonic epithelial cells. DNA Cell Biol 25(1):49–62

    Article  PubMed  CAS  Google Scholar 

  16. Pool-Zobel BL, Selvaraju V, Sauer J, Kautenburger T, Kiefer J, Richter KK, Soom M, Wolfl S (2005) Butyrate may enhance toxicological defence in primary, adenoma and tumor human colon cells by favourably modulating expression of glutathione S-transferases genes, an approach in nutrigenomics. Carcinogenesis 26(6):1064–1076

    Article  PubMed  CAS  Google Scholar 

  17. Beyer-Sehlmeyer G, Glei M, Hartmann E, Hughes R, Persin C, Bohm V, Rowland I, Schubert R, Jahreis G, Pool-Zobel BL (2003) Butyrate is only one of several growth inhibitors produced during gut flora-mediated fermentation of dietary fibre sources. Br J Nutr 90(6):1057–1070

    Article  PubMed  CAS  Google Scholar 

  18. Stowell JD (2009) Polydextrose. In: Sungsoo S, Samuel P (eds) Fiber ingredients, food applications and health benefits. CRC Press, Boca Raton, pp 173–201

    Google Scholar 

  19. Makivuokko H, Nurmi J, Nurminen P, Stowell J, Rautonen N (2005) In vitro effects on polydextrose by colonic bacteria and caco-2 cell cyclooxygenase gene expression. Nutr Cancer 52(1):94–104

    Article  PubMed  CAS  Google Scholar 

  20. Nurmi JT, Puolakkainen PA, Rautonen NE (2005) Intron 1 retaining cyclooxygenase 1 splice variant is induced by osmotic stress in human intestinal epithelial cells. Prostaglandins Leukot Essent Fatty Acids 73(5):343–350

    Article  PubMed  CAS  Google Scholar 

  21. Team RDC (2006) R: a language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria

  22. Gentleman RC, Carey VJ, Bates DM, Bolstad B, Dettling M, Dudoit S, Ellis B, Gautier L, Ge Y, Gentry J, Hornik K, Hothorn T, Huber W, Iacus S, Irizarry R, Leisch F, Li C, Maechler M, Rossini AJ, Sawitzki G, Smith C, Smyth G, Tierney L, Yang JY, Zhang J (2004) Bioconductor: open software development for computational biology and bioinformatics. Genome Biol 5(10):R80

    Article  PubMed  Google Scholar 

  23. Langsrud O (2002) 50–50 multivariate analysis of variance for collinear responses. J R Stat Soc D 51:305–317

    Article  Google Scholar 

  24. Davis CD, Milner JA (2009) Gastrointestinal microflora, food components and colon cancer prevention. J Nutr Biochem 20(10):743–752

    Article  PubMed  CAS  Google Scholar 

  25. Yang SY, Sales KM, Fuller B, Seifalian AM, Winslet MC (2009) Apoptosis and colorectal cancer: implications for therapy. Trends Mol Med 15(5):225–233. doi:10.1016/j.molmed.2009.03.003

    Article  PubMed  CAS  Google Scholar 

  26. Pajak B, Gajkowska B, Orzechowski A (2009) Sodium butyrate sensitizes human colon adenocarcinoma COLO 205 cells to both intrinsic and TNF-alpha-dependent extrinsic apoptosis. Apoptosis 14(2):203–217. doi:10.1007/s10495-008-0291-9

    Article  PubMed  CAS  Google Scholar 

  27. Vakifahmetoglu-Norberg H, Zhivotovsky B (2010) The unpredictable caspase-2: what can it do? Trends Cell Biol 20(3):150–159

    Article  PubMed  CAS  Google Scholar 

  28. Martinasso G, Oraldi M, Trombetta A, Maggiora M, Bertetto O, Canuto RA, Muzio G (2007) Involvement of PPARs in cell proliferation and apoptosis in human colon cancer specimens and in normal and cancer cell lines. PPAR Res 2007:93416

    Article  PubMed  CAS  Google Scholar 

  29. Mutoh M, Niho N, Wakabayashi K (2006) Concomitant suppression of hyperlipidemia and intestinal polyp formation by increasing lipoprotein lipase activity in Apc-deficient mice. Biol Chem 387(4):381–385. doi:10.1515/bc.2006.051

    Article  PubMed  CAS  Google Scholar 

  30. Feilchenfeldt J, Brundler MA, Soravia C, Totsch M, Meier CA (2004) Peroxisome proliferator-activated receptors (PPARs) and associated transcription factors in colon cancer: reduced expression of PPAR[gamma]-coactivator 1 (PGC-1). Cancer Lett 203(1):25–33

    Article  PubMed  CAS  Google Scholar 

  31. Li TG, Chiang JYL (2009) Regulation of bile acid and cholesterol metabolism by PPARs. PPAR Res

  32. Schwab U, Louheranta A, Torronen A, Uusitupa M (2006) Impact of sugar beet pectin and polydextrose on fasting and postprandial glycemia and fasting concentrations of serum total and lipoprotein lipids in middle-aged subjects with abnormal glucose metabolism. Eur J Clin Nutr 60(9):1073–1080

    Article  PubMed  CAS  Google Scholar 

  33. Aller R, de Luis DA, Izaola O, La Calle F, del Olmo L, Fernandez L, Arranz T, Hernandez JMG (2004) Effect of soluble fiber intake in lipid and glucose leves in healthy subjects: a randomized clinical trial. Diabetes Res Clin Pract 65(1):7–11

    Article  PubMed  CAS  Google Scholar 

  34. Wu K, Bowman R, Welch AA, Luben RN, Wareham N, Khaw KT, Bingham SA (2007) Apolipoprotein E polymorphisms, dietary fat and fibre, and serum lipids: the EPIC Norfolk study. Eur Heart J 28(23):2930–2936

    Article  PubMed  CAS  Google Scholar 

  35. Marcil V, Delvin E, Seidman E, Poitras L, Zoltowska M, Garofalo C, Levy E (2002) Modulation of lipid synthesis, apolipoprotein biogenesis, and lipoprotein assembly by butyrate. Am J Physiol Gastrointest Liver Physiol 283(2):G340–G346

    PubMed  CAS  Google Scholar 

  36. Arora T, Sharma R, Frost G (2011) Propionate. Anti-obesity and satiety enhancing factor? Appetite 56(2):511–515. doi:10.1016/j.appet.2011.01.016

    Article  PubMed  Google Scholar 

  37. Field FJ, Watt K, Mathur SN (2008) Origins of intestinal ABCA1-mediated HDL-cholesterol. J Lipid Res 49(12):2605–2619

    Article  PubMed  CAS  Google Scholar 

  38. Hayashi H, Sakamoto M, Benno Y (2002) Phylogenetic analysis of the human gut microbiota using 16S rDNA clone libraries and strictly anaerobic culture-based methods. Microbiol Immunol 46(8):535–548

    PubMed  CAS  Google Scholar 

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Acknowledgments

The authors wish to acknowledge Ilana Saarikko (Pharmatest Services Ltd) for contribution in the data analysis. Henna Röytiö (Danisco Health & Nutrition) is thanked for supplying unpublished data and PDX simulation samples.

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Author notes

  1. Harri Mäkivuokko

    Present address: The Finnish Red Cross Blood Service, R&D, Kivihaantie 7, 00310, Helsinki, Finland

Authors and Affiliations

  1. Danisco Health & Nutrition, Sokeritehtaantie 20, 02460, Kantvik, Finland

    Heli Putaala, Harri Mäkivuokko, Kirsti Tiihonen & Nina Rautonen

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  1. Heli Putaala
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  2. Harri Mäkivuokko
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Correspondence to Heli Putaala.

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Putaala, H., Mäkivuokko, H., Tiihonen, K. et al. Simulated colon fiber metabolome regulates genes involved in cell cycle, apoptosis, and energy metabolism in human colon cancer cells. Mol Cell Biochem 357, 235–245 (2011). https://doi.org/10.1007/s11010-011-0894-2

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