| Colorectal cancer is still the third most commonly diagnosed cancer worldwise, each year about 1.2 million people are diagnosed with colorectal cancer, according to World Cancer Report 2014. In China, the incidence of colorectal cancer tends to increase every year, but the therapy is still poor. There is a great massive of micro flora in intestine which can reach a quantity of 1014 and is comprised of more than 1000 species. A majority of them are belong to Firmicutes and Bacteroidel.es and they participate in many human physiological activities and metabolism including the digestion of food, the supply of energy for colonic epithelial cells, and the regulation of immune response. Structural changes or quantitative changes in the gut microbial community alter the permeability of intestine and lead to the inflammatory bowel disease, even the progressive development of colorectal cancer.Black raspberry (BRB) belongs to RubuscorchorifoliusL.f. and has been proved with abundant active substances like, phenolic acids, flavonoids, procyanidins, tannic acid, styrene, wooden fat element, terpene and sterol, etc. Dietary polyphenols and its metabolites balance the gut microbes and, in turn, affect the occurrence and development of colorectal cancer by adjusting the growth of probiotics and pathogenic bacteria, but the corresponding data are not reported. So this study was aimed to investigate the effect of polyphenols from BRB on the regulation of intestinal microflora and its possible mechanism, which may lay the foundation for intestinal microflora as a new tumor marker.The results we found were showed as below:(1)BRB polyphenols regulated intestinal microflora of colorectal cancer in mice:With chemical reagent AOM (methane oxidation azo) and DSS (dextran sodium sulfate) induced formation of colorectal tumor mouse model.5%and 10%for colorectal tumor mouse model mixed BRB polyphenols feed with 9 weeks. We found that the Control group (Control) and BRB polyphenols treatment group (5%BRB and 10% BRB) samples gathered together into a cluster, in addition to the individual colorectal tumor samples of Model group (Model) in mice, which shows that high composition similarity of intestinal microflora community in Control,5% BRB and 10% BRB, and low composition similarity to Model. Groups of intestinal bacteria in the richness, diversity, evenness index had no significant difference, while the number of the same intestinal flora had significant difference. Results showed that BRB polyphenols promote the growth of beneficial intestinal microflora and inhibit the growth of intestinal pathogenic microflora. So BRB polyphenols change the number of intestinal flora, in turn, affects the occurrence and development of colorectal cancer.(2) The mechanism of BRB polyphenols regulated the intestinal flora of colorectal tumor mice:The occurrence of colorectal cancer was caused by inflammation, so model of colorectal tumors induced by AOM/DSS simulate the process of inflammatory bowel disease to colorectal cancer. In this research, we detected the expression of following inflammatory factors:IL-1, IL-6, IL-10, COX2 and TNF-α, the key factor of the inflammation associated with tumor:STAT3, JNK, Bcl2, Bax, CDK4, CyclinDl, c-Myc and 3-catenin to analysis possible mechanisms of BRB polyphenols in the regulation of intestinal microflora in mice. Results show that the expression levels of inflammatory factors on 5% BRB and 10%BRB were reduced. In addition, BRB polyphenols regulated STAT3 signaling pathway on key protein expression of colorectal tumor mice, which indicated that in the case of intestinal flora disturbance BRB polyphenol regulate the development of CRC from this signaling pathway.(3)Regulation of BRB polyphenols the intestinal microflora in colorectal tumor mice in vitro:Treated with different concentrations of BRB polyphenols in vitro intestinal flora, the results showed that with the increase of the concentration of BRB polyphenols, bacteriostatic rate also gradually enhanced, which suggest that BRB polyphenols still have antibacterial activity in vitro.To sum up, BRB polyphenols regulate intestinal microbiota, reduce the levels of inflammatory cytokines and improve the development of CRC through inhibition of the STAT3-signaling pathway. |
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