Polysaccharides Target Gut Microbiota to Suppress NOD2-Driven Inflammation and Modulate Bile Acid Metabolism in Colitis.

, a traditional medicinally edible herb, exhibits potent anti-inflammatory activity. Its primary active components are fermentable polysaccharides, which enhance the proliferation of beneficial gut microbiota. However, the role of the gut microbiota in the anti-inflammatory effects of polysaccharides (PCPs) has not been adequately explored, and the mechanisms involved remain largely unelucidated. Our results demonstrated that PCP significantly alleviated DSS-induced colitis symptoms and enhanced beneficial gut microbiota abundance and diversity. Notably, gut microbiota modulated by PCP exhibited a similar capacity to mitigate colitis symptoms. Further mechanistic studies revealed that both PCP and the PCP-modulated gut microbiota improved colitis by inhibiting the overactivation of the NOD2-mediated autophagy-inflammation pathway and reducing the synthesis of the bile acid metabolite LTC4. Importantly, LTC4 levels were positively correlated to the NOD2-autophagy-inflammation pathway. Collectively, our findings identified PCP as a novel prebiotic preserving gut health through microbiota-mediated homeostasis regulation, offering new therapeutic strategies for inflammatory disorders.