Mechanisms of primary cancer prevention by butyrate and other products formed during gut flora-mediated fermentation of dietary fibre

Institute for Nutrition, Friedrich Schiller University Jena, Dornburger Strasse 24, 07743 Jena, Germany.
Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis (Impact Factor: 3.68). 05/2009; 682(1):39-53. DOI: 10.1016/j.mrrev.2009.04.001
Source: PubMed


Dietary fibres are indigestible food ingredients that reach the colon and are then fermented by colonic bacteria, resulting mainly in the formation of short-chain fatty acids (SCFA) such as acetate, propionate, and butyrate. Those SCFA, especially butyrate, are recognised for their potential to act on secondary chemoprevention by slowing growth and activating apoptosis in colon cancer cells. Additionally, SCFA can also act on primary prevention by activation of different drug metabolising enzymes. This can reduce the burden of carcinogens and, therefore, decrease the number of mutations, reducing cancer risk. Activation of GSTs by butyrate has been studied on mRNA, protein, and enzyme activity level by real-time RT-PCR, cDNA microarrays, Western blotting, or photometrical approaches, respectively. Butyrate had differential effects in colon cells of different stages of cancer development. In HT29 tumour cells, e.g., mRNA GSTA4, GSTP1, GSTM2, and GSTT2 were induced. In LT97 adenoma cells, GSTM3, GSTT2, and MGST3 were induced, whereas GSTA2, GSTT2, and catalase (CAT) were elevated in primary colon cells. Colon cells of different stages of carcinogenesis differed in post-transcriptional regulatory mechanisms because butyrate increased protein levels of different GST isoforms and total GST enzyme activity in HT29 cells, whereas in LT97 cells, GST protein levels and activity were slightly reduced. Because butyrate increased histone acetylation and phosphorylation of ERK in HT29 cells, inhibition of histone deacetylases and the influence on MAPK signalling are possible mechanisms of GST activation by butyrate. Functional consequences of this activation include a reduction of DNA damage caused by carcinogens like hydrogen peroxide or 4-hydroxynonenal (HNE) in butyrate-treated colon cells. Treatment of colon cells with the supernatant from an in vitro fermentation of inulin increased GST activity and decreased HNE-induced DNA damage in HT29 cells. Additional animal and human studies are needed to define the exact role of dietary fibre and butyrate in inducing GST activity and reducing the risk of colon cancer.

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Available from: Michael Glei, Jul 22, 2014
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    • "Improving gut fermentation may improve gut barrier function and reduce chronic inflammation of the gut (Keenan et al., 2012) and may protect against red meat-induced colonic DNA damage (Toden, Bird, Topping, & Conlon, 2006). The enhancement of butyrate producing bacteria has also been shown to reduce cancer risk in animal models (Scharlau et al., 2009). While there has been an explosion of efforts to characterize gut microbial population in healthy and disease states, there is a need to look further than just the type of species that is present in the gut, and instead focus on understanding functional significance of microbiota changes. "
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    • "A high-fiber diet consists mainly of vegetables, fruits, and grains. Their presence in meals contributes to decreased transit time through the gastrointestinal tract, dilution of colonic contents, and enhancement of bacterial fermentation, which leads to increased production of short-chain fatty acids (acetate, propionate, and butyrate) [9]. Moreover, these substances were found to induce apoptosis in CRC cells in rats [10]. "
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    • "Consequently, the potential physiological and pathological effects of propionic acid have long been underestimated [14]. Butyrate causes apoptosis, reduces metastasis of colon cell lines, and protects against genotoxic carcinogens [20]. Elevated butyric acid concentrations observed in the DMH+PRE group is in accordance with experimental animal models which revealed that inulin-type fructans have anticarcinogenic properties [18]. "
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