Regulation of gut microbiota involved in the chemoprevention effects of Black raspberry polyphenols on colorectal cancer

Abstract

Frozen black raspberry powder has been regarded with interest as possible chemopreventive agents against cancer. Here we report that black raspberry (BRB) polyphenols administered with the diet to C57BL/6J mice for 12 weeks inhibited colon carcinogenesis induced by AOM/DSS. Polyphenol-treated animals had a consistently lower tumor multiplicies compared to controls. In AOM/DSS induced mice, the main bacterial strains in the faeces at sacrifice were pathogenic bacterium including Haemophilus, Escherichia coli and Salmonella enterica, whereas the microorganisms predominantly identified after the period of black raspberry polyphenols supplement mice were Butyrate producing bacteria. Inflammatory cytokines including IL-1, IL-6, IL-10, COX-2 and TNF-α were found significantly reduced in BRB polyphenols supplemented group mice. The most interesting finding is the epigenetic status was found could be modulated by the polyphenols, the enzymes SIRTs and DNMTs associated with acetylation and methylation were decreased significantly. Furthermore, the level of p-STAT3, β-catenin and their downstream targets were obviously down-regulated at protein levels by BRB polyphenols. In conclusion, modulation of gut microbiota, reduction of inflammatory cytokines, and alterations of epigenetic status and the followed genes expression may all concur in the modulation of intestinal function and carcinogenesis by BRB polyphenols.