[Tremella fuciformispolysaccharide retards the progression of colorectal cancer by regulating the gut microbiota-metabolome axis].

Objective: To investigate the anti-colorectal cancer effect of tremella fuciformis polysaccharides (TFP) via the gut microbiota-metabolite axis. Methods: Colorectal cancer was induced in C57BL/6J mice using azoxymethane/dextran sulfate sodium. TFP or distilled water was administered by gavage for 3 weeks. Disease activity index (DAI), colon length, tumor burden, histopathology, gut microbiota (metagenomics), fecal metabolites (untargeted metabolomics), and colonic protein expression (Western blot) were assessed. Pyridoxic acid's effect on HT-29 cells was tested in vitro. Results: TFP significantly reduced DAI [2.0(1.8, 3.3) vs. 3.5(2.8, 4.5), P＜0.01], increased colon length [(7.2±1.1) vs. (5.5±0.5) cm, P＜0.05], lowered pathological score [6(3, 8) vs. 9(8, 10), P＜0.05], and decreased tumor number [2(1, 3) vs. 4(3, 4), P＜0.05] and volume [(11.02±7.88) vs. (24.99±3.38), P＜0.01]. Metagenomics revealed that TFP significantly reshaped gut microbiota (R²=0.173, P=0.027), enriching Candidatus Amulumruptor, Helicobacter, and Akkermansia. Metabolomics showed distinct profiles (R²=0.159, P=0.004), with pyridoxic acid elevated 1.20 fold (P＜0.001). Pyridoxic acid suppressed HT-29 cell viability and migration, and correlated positively with several upregulated bacteria, suggesting a microbiota-metabolite axis underlying its anti-tumor effect. TFP downregulated nuclear factor-κB (NF-κB) (P＜0.01) and upregulated phosphorylated AMP-activated protein kinase alpha (p-AMPKα) (P＜0.001), BAX (P＜0.001), and cleaved caspase-3 (P＜0.05). Conclusion: TFP inhibits colorectal cancer progression by modulating gut microbiota, elevating pyridoxic acid, suppressing NF-κB, and activating AMPK-mediated apoptosis.