Prebiotics are considered as non-digestible food ingredients that stimulate the growth of beneficial gut bacteria, thus contribute to the health of the host. Recent evidences have suggested that prebiotics treatment may become one of the key therapeutic strategies for many diseases, especially for cancer. In our previous studies, both Gynostemma pentaphyllum saponin (GpS) and Ganoderma lucidum polysaccharides (GlP) demonstrated significant prebiotic effects in mouse models. In addition, GpS alone exerted significant anti-tumor effect by restoring the dysbiosis of the gut microbiota and microenvironment of the ApcMin/+mice. Thus, we hypothesized that supplement with GlP might enhance the anti-cancer effect of GpS through the modulation of the gut microbiota. To test the hypothesis, we treated ApcMin/+mice with four different treatments, i.e. GlP (750mg/kg), GpS (300mg/kg), GlP (750mg/kg) + GpS (300mg/kg) and the drinking water control. The results showed that GlP+GpS was more effective in suppressing the polyp growth compared to the GpS or GlP groups. GlP+GpS also improved the health of gut barriers by inducing Paneth cells and goblet cells, and reinstating the E-cadherin and N-cadherin expressions in a greater extend compared to the other groups. All treatments facilitated the polarization of M1 macrophage to M2 macrophage, and increased the anti-inflammatory cytokines (IL-4 and IL-10). Interestingly, expressions the SCFA receptors, GPR 43, 49 and 119 were markedly elevated in all treatment groups, with the most prominent expression observed in the GlP+GpS group. 16S rRNA sequencing data were analyzed by using alpha diversity analysis and weighted UniFrac distance analysis. Differential alterations of the composition of gut microbiota were observed in all treatment groups. Certain bacteria (Anoerodtipe, Bacteroides, Clostridium, Citribacter, Subdoligranulum, C.

leptum) associated colitis and colorectal carcinoma were significant decreased, while some SCFA-producing bacteria (Blautia sp., Eubacterium saphenum, Clostridium aminobutyricum) were enhanced in the treated groups. We concluded that the anti-tumor effects of GpS and GlP might be in part through the modulation of the gut microbiota and the improvement of epithelial microenvironment, and the stronger effects were produced by the GpS+ GlP combined treatment.

[This study was supported by Macau FDCT 015/2014/A1 and 103/2016/A3]

Citation Format: Xiao-ang Li, Guoxin Huang Huang, Imran Khan, Wen-rui Xia, Wai kit Leong, W.L. Wendy Hsiao. Cooperative effects of mushroom polysaccharides and herbal saponins on tumor growth and gut microenvironment in ApcMin/+mice [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5144.