Abstract
Studies showed that manipulation of gut microbiota (GM) composition through the treatment of prebiotics could be a novel preventive measure against colorectal cancer (CRC) development. In this study, for the first time, we assessed the non-toxic doses of the triterpene saponins (ginsenoside-Rb3 and ginsenoside-Rd) – as prebiotics – that effectively reinstated the dysbiotic-gut microbial composition and intestinal microenvironment in an ApcMin/+ mice model. Rb3 and Rd effectively reduced the size and the number of the polyps that accompanied with the downregulation of oncogenic signaling molecules (iNOS, STAT3/pSTAT3, Src/pSrc). Both the compounds improved the gut epithelium by promoting goblet and Paneth cells population and reinstating the E-cadherin and N-Cadherin expression. Mucosal immunity remodeled with increased in anti-inflammatory cytokines and reduced in pro-inflammatory cytokines in treated mice. All these changes were correlating with the promoted growth of beneficial bacteria such as Bifidobacterium spp., Lactobacillus spp., Bacteroides acidifaciens, and Bacteroides xylanisolvens. Whereas, the abundance of cancer cachexia associated bacteria, such as Dysgonomonas spp. and Helicobacter spp., was profoundly lower in Rb3/Rd-treated mice. In conclusion, ginsenosides Rb3 and Rd exerted anti-cancer effects by holistically reinstating mucosal architecture, improving mucosal immunity, promoting beneficial bacteria, and down-regulating cancer-cachexia associated bacteria.
Highlights
colorectal cancer (CRC) is ranked second among all the cancer incidences worldwide
We showed that Gynostemma pentaphyllum (Gp) saponins (GpS) significantly reduced tumors growth and count in both nude mice and ApcMin/+ mice[21,22]
Ginsenosides Rb3 and Rd are two major compounds isolated from Gynostemma pentaphyllum that holistically improved gut microenvironment and induced anti-polyposis in ApcMin/+ mice
Summary
CRC is ranked second among all the cancer incidences worldwide. Among USA population, approximately 4.3 percent of men and woman are diagnosed for colon and rectum cancer at some point during their lifetime[1]. Epidemiological and animal studies have indicated that western high fat diet is believed to be the key risk factor responsible for the high incidence of CRC2,3. This observation was supported by the recent findings in which high animal fat diet altered the gut microbial composition, leading to microbial dysbiosis and inflamed gut epithelium[4,5,6]. The dynamic interplay between the GM and the ingested dietary compounds impacts on cancer risk and treatment. For this reason, probioticsand prebiotics-based GM modifications have been proposed as an alternative approach for the treatment and prevention of CRC18. Immunohistochemistry, qRT-PCR and Western blot were employed to determine changes in mucosal cytokines and intestinal architecture
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