(P13-018-23) Conditioned Medium of Turicibacter Cultured With Antrodia camphorata Polysaccharide Inhibits Tumorigenic Serotonin and Wnt Pathways and Promotes Apoptosis of Caco-2 Cells

Objectives: Interesting evidence from our previous work suggests that diet-induced obesity is associated with diminished abundance of an understudied genus Turicibacter in the gut microbiota. Limited work also indicates that Turicibacter may be involved in the serotonin-signaling system, which is associated with colorectal tumorigenesis. Antrodia Camphorata, (AC) is a medicinal fungus that may contain complementary polysaccharides for Western diet and reportedly has anti-cancer property. This study aims to determine the role of Turicibacter in colorectal tumorigenesis and to explore the anti-cancer mechanism of AC with Turicibacter fermentation.

Methods: Caco-2 cells were cultured with four cell-free supernatants collected from bacterial culture media: bacterial culture medium only (CM), medium with AC polysaccharide (ACCM), Turicibacter cultured medium (TCM), and Turicibacter cultured medium with AC polysaccharide (TACCM). The nutrients and metabolites in the four media were measured, and the influences of Turicibacter and AC polysaccharide on serotonin signaling, Wnt-signaling and cell apoptosis were explored.

Results: The Turicibacter fermentation and the addition of AC polysaccharide resulted in a significant increase in a number of nutrients and metabolites, including lactic acid and α-ketoglutaric acid (p < 0.05). Compared to other groups, treatment with TACCM showed more effective inhibitory effects on serotonin signaling as indicated by decreased expressions of Tph1, Htr1d, Htr2a, Htr2b and Htr2c (p < 0.05), and Wnt-signaling as manifested by altered expression of phospho-GSK-3β, active β-catenin, cMyc, Ccnd1 and Axin2 (p < 0.05). Moreover, TACCM triggered the highest generation of reactive oxygen species (ROS), the highest ROS-mediated Akt and MAPK signaling, and cleaved caspase-3 expression.

Conclusions: Antrodia Camphorata polysaccharide effectively suppresses the tumorigenic serotonin and Wnt signalings, and promotes ROS-mediated apoptosis in Caco-2 cells, which are at least partially modulated by Turicibacter fermentation.

Funding Sources: This material is based upon work supported in part by USDA/NIFA AFRI grants (2022-67018-36986, ZL) and USDA//NIFA Hatch project (MAS00586, ZL). The contents are solely the responsibility of the authors and do not necessarily represent the official views of the USDA or NIFA.