Simulated colon fiber metabolome regulates genes involved in cell cycle, apoptosis, and energy metabolism in human colon cancer cells
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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.
KeywordsColon cancer Fiber Microarray Polydextrose Simulation
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 Henna Röytiö (Danisco Health & Nutrition) is thanked for supplying unpublished data and PDX simulation samples.
- 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 PubMedCrossRefGoogle 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
- 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):1064–1076PubMedCrossRefGoogle Scholar
- 18.Stowell JD (2009) Polydextrose. In: Sungsoo S, Samuel P (eds) Fiber ingredients, food applications and health benefits. CRC Press, Boca Raton, pp 173–201Google Scholar
- 21.Team RDC (2006) R: a language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, AustriaGoogle Scholar
- 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):R80PubMedCrossRefGoogle Scholar
- 31.Li TG, Chiang JYL (2009) Regulation of bile acid and cholesterol metabolism by PPARs. PPAR ResGoogle Scholar
- 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):1073–1080PubMedCrossRefGoogle Scholar