Butyrylated starch affects colorectal cancer markers beneficially and dose-dependently in genotoxin-treated rats

Abstract

Abbreviations: AI, apoptotic index; AOM, azoxymethane; HAMS, high amylose maize starch; HAMSB butyrylated high amylose maize starch; HAMSB0, base diet containing 0% HAMSB; HAMSB5, base diet containing 5% HAMSB; HAMSB10, base diet containing 10% HAMSB; HAMSB20, base diet containing 20% HAMSB; HAMSB40, base diet containing 40% HAMSB; RS, resistant starch; SCFA, short chain fatty acid; SSB, single-stranded DNA breaksPopulation studies suggest that greater dietary fiber intake may lower colorectal cancer (CRC) risk, possibly through the colonic bacterial fermentative production of butyrate. Butyrylated starch delivers butyrate to the colon of humans with potential to reduce CRC risk but high doses may exacerbate risk through promoting epithelial proliferation. Here we report the effects of increasing dietary butyrylated high amylose maize starch (HAMSB) on azoxymethane (AOM) induced distal colonic DNA damage, cell proliferation, mucus layer thickness and apoptosis in rats. Five groups of 15 rats were fed AIN-93G based diets containing 0-40% HAMSB for 4 weeks then injected with (AOM) and killed 6 hours later. Large bowel total SCFA, acetate and butyrate pools and hepatic portal venous plasma total SCFA, acetate and butyrate concentrations were higher with greater HAMSB intake. Distal colonic epithelial apoptotic index and colonic mucus thickness increased, while DNA single strand breaks decreased dose-dependently with greater HAMSB intake. Colonocyte proliferation rates were unaffected by diet. These data suggest that increasing large bowel butyrate may reduce the risk of CRC in a dose dependent manner by enhancing apoptotic surveillance in the colonic epithelium for damaged cells without promoting the risk of tumorigenesis through increased cell proliferation.

Comparative In silico Analysis of Butyrate Production Pathways in Gut Commensals and Pathogens

“…These studies suggest that butyrate produced by gut bacteria has a positive influence on gut health. Studies have indicated that butyrate obtained from natural dietary fiber can help maintain gut homeostasis and reduce the idiopathies of various diseases that develop due to dysbiosis (Toden et al, 2014). …”

Colon Cancer Chemoprevention by Sage Tea Drinking: Decreased DNA Damage and Cell Proliferation

“…Beneficial effects of other plant foods have been found, for example, black tea and wine extracts, but not green tea have shown to protect against AOMinduced colon carcinogenesis in rats (Caderni et al, 2000) and theaflavin-2, a major compound found in black tea extract was shown to induce apoptosis in human colon cell lines (Gosslau et al, 2011). Butyrate may reduce the risk of CRC in a dose dependent manner by enhancing apoptosis for damaged cells without promoting the risk of tumorigenesis through increased cell proliferation (Toden et al, 2014). In a study by Andersson et al, 2008(Andersson et al, 2008, ursolic acid, a pentacyclic triterpenoid also present in SO, was found to reduce the number of large ACF when given orally to rats during the initiation phase but not during the promotion/progression phase, results that are in agreement with our present study.…”

Epigenetic Regulation of Gene Expression Induced by Butyrate in Colorectal Cancer: Involvement of MicroRNA

“…Evidence from animal trials and in vitro studies supports the anti-tumorigenic effects of butyrate. 24 , 29 , 46 In an animal model study conducted by Shen et al, 47 HDACi upregulated selective miRNAs to modulate B-cell differentiation and the immune response of the host. In vivo and in vitro studies found that butyrate can also modulate the inflammatory response by the suppression of nuclear factor κB activation.…”