Ginseng-derived nanocellulose alleviates murine colitis through modulation of inflammation, epithelial barrier and gut microbiome

• GNFs were optimized by evaluating various preparation methods. • GNFs inhibited inflammatory TLR4-PI3K/AKT-NF-κB signaling pathway. • GNFs modulate gut microbiota , and increased beneficial bacteria. • GNFs enhanced intestinal retention as drug delivery platform. • GNFs could serve as a promising dietary prebiotic . Nanocellulose has shown potential for inflammatory modulation. However, limited research exists on the extraction and utilization of plant-derived nanocellulose, particularly from medicinal sources like ginseng, for treating inflammatory diseases such as ulcerative colitis (UC). Current UC treatments are often associated with side effects and limited therapeutic efficacy, making nanocellulose-based therapy a promising alternative. Herein, we extracted ginseng-derived nanofibers (GNFs) from ginseng solid residues and systematically screened different preparation methods. We evaluated their therapeutic potential in a dextran sulfate sodium (DSS)-induced model. GNFs inhibited key inflammatory pathways, including TLR4-medaited PI3K/AKT-NF-κB signaling, while promoting epithelial barrier restoration, which was further validated using organoid models. 16S rRNA sequencing and metabolomics revealed that GNFs administration restored gut microbiota balance by modulating microbial diversity and abundance, and influenced key metabolic pathways associated with inflammation. Additionally, GNFs enhanced the intestinal retention and therapeutic efficacy of 5-ASA, demonstrating their dual role as a therapeutic agent and drug delivery platform. These findings suggest that GNFs offer a new strategy for UC management, with broader implications for gastrointestinal health.