Figure 8. Summary of the impacts of GpS on host-gut-microbiota in Apc^Min/+ mice.

GpS impacts on host-gut-microbiota homeostasis through various means. GpS treatment increases beneficial bacteria, decreases sulfate-reducing bacteria, and improves gut epithelial barrier, which might contribute to its cancer preventive effects. The protective effects of GpS on the gut epithelial barrier (box in solid lines) might be partially through the induction of IL-4 secretion. On one hand, the elevation of IL-4 stimulates the M1 to M2 macrophages switching and facilitates intestinal tissue repair. On the other hand, IL-4 expression can also suppress the M1 induced marker, iNOS and reduce the chronic inflammation in the gut epithelial barrier. The elevated IL-4 cytokine might account for downregulation of p-Src and p-STAT3. As a result, it positively regulates E-cadherin and negatively modulates N-cadherin, presenting a reversion of disease to health status of gut epithelium upon GpS treatment. GpS also seems to improve of the intestinal epithelium by increasing Paneth and goblet cells. E-cadherin is required for Paneth cell maturation, while IL-4 can induce mucin secretion in goblet cells. The enrichment of goblet and Paneth cells facilitates the MCP-1 production and contributes to the tissue repair. Black arrows: pathways; red arrows: up-regulation; blue arrows: down-regulation; dashed lines: increase production.