Turicibacter fermentation enhances the inhibitory effects of Antrodia camphorata supplementation on tumorigenic serotonin and Wnt pathways and promotes ROS-mediated apoptosis of Caco-2 cells

Diet-induced obesity has been shown to decrease the abundance of , a genus known to play a role in the serotonin signaling system, which is associated with colorectal tumorigenesis, making the presence of potentially influential in the protection of intestinal tumorigenesis. Recently, (AC), a medicinal fungus native to Taiwan, has emerged as a promising candidate for complementary and alternative cancer therapy. Small molecules and polysaccharides derived from AC have been reported to possess health-promoting effects, including anti-cancer properties. Bacterial culture followed with cell culture were used in this study to determine the role of in colorectal tumorigenesis and to explore the anti-cancer mechanism of AC with fermentation. fermentation and the addition of AC polysaccharide led to a significant increase in the production of nutrients and metabolites, including α-ketoglutaric acid and lactic acid ( < 0.05). Treatment of fermented AC polysaccharide was more effective in inhibiting serotonin signaling-related genes, including , and ( < 0.05), and -signaling related protein and downstream gene expressions, such as phospho-GSK-3β, active β-catenin, ( < 0.05). Additionally, it triggered the highest generation of reactive oxygen species (ROS), which activated PI3K/Akt and MAPK/Erk signaling and resulted in cleaved caspase-3 expression. In comparison, the treatment of AC polysaccharide without fermentation displayed a lesser effect. Our findings suggest that AC polysaccharide effectively suppresses the tumorigenic serotonin and -signaling pathways, and promotes ROS-mediated apoptosis in Caco-2 cells. These processes are further enhanced by fermentation.