引言：已经证明通过饮食诱导肥胖会减少肠道肿瘤生成相关的血清素信号系统的种群——杜利西巴克菌的丰度，从而使得杜利西巴克菌的存在在保护肠道肿瘤生成方面具有潜在影响。最近，一种原产于台湾的药用真菌——槲寄生（简称AC）被发现是一种备受期待的辅助和替代癌症治疗候选药物。从槲寄生中提取的小分子和多糖被报道具有促进健康的效果，包括抗癌作用。方法：本研究采用细菌培养和细胞培养相结合的方法，确定杜利西巴克菌在结直肠肿瘤生成中的作用，并探索与杜利西巴克菌发酵相关的槲寄生的抗癌机制。结果：杜利西巴克菌发酵和添加槲寄生多糖显著增加了营养物质和代谢物的产量，包括α-酮戊二酸和乳酸（p < 0.05）。用杜利西巴克菌发酵的槲寄生多糖处理在抑制与血清素信号相关的基因（包括Tph1、Htr1d、Htr2a、Htr2b和Htr2c，p < 0.05）以及与Wnt信号相关的蛋白和下游基因表达（如磷酸化GSK-3β、活性β-连环蛋白、c-Myc、Ccnd1和Axin2，p < 0.05）方面更为有效。此外，它引发了最高水平的活性氧（ROS），激活了PI3K/Akt和MAPK/Erk信号通路，并导致了剪切的半胱氨酸酶-3表达。相比之下，未经杜利西巴克菌发酵处理的槲寄生多糖处理效果较差。讨论：我们的研究结果表明，槲寄生多糖有效地抑制了与肿瘤生成相关的血清素和Wnt信号通路，并促进了Caco-2细胞中ROS介导的凋亡。这些过程进一步通过杜利西巴克菌发酵得到增强。版权所有 © 2023 Lin, Soorneedi, Guan, Tang, Shi, Moore and Liu.

Introduction: Diet-induced obesity has been shown to decrease the abundance of Turicibacter, a genus known to play a role in the serotonin signaling system, which is associated with colorectal tumorigenesis, making the presence of Turicibacter potentially influential in the protection of intestinal tumorigenesis. Recently, Antrodia camphorata (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. Methods: Bacterial culture followed with cell culture were used in this study to determine the role of Turicibacter in colorectal tumorigenesis and to explore the anti-cancer mechanism of AC with Turicibacter fermentation. Results: Turicibacter 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 (p < 0.05). Treatment of Turicibacter fermented AC polysaccharide was more effective in inhibiting serotonin signaling-related genes, including Tph1, Htr1d, Htr2a, Htr2b, and Htr2c (p < 0.05), and Wnt-signaling related protein and downstream gene expressions, such as phospho-GSK-3β, active β-catenin, c-Myc, Ccnd1, and Axin2 (p < 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 Turicibacter fermentation displayed a lesser effect. Discussion: Our findings suggest that AC polysaccharide effectively suppresses the tumorigenic serotonin and Wnt-signaling pathways, and promotes ROS-mediated apoptosis in Caco-2 cells. These processes are further enhanced by Turicibacter fermentation.Copyright © 2023 Lin, Soorneedi, Guan, Tang, Shi, Moore and Liu.