Taraxacum-derived extracellular nanovesicles attenuate dss-induced colitis through coordinated modulation of gut microbiota, intestinal barrier, and mucosal inflammation

Abstract

Ulcerative colitis (UC) is a chronic inflammatory disease of the colon associated with dysregulated mucosal immunity and gut microbiota imbalance. Safe and effective long-term treatment options remain limited. In this study, we isolated Taraxacum-derived extracellular nanovesicles (TENVs) and evaluated their effects in a dextran sulfate sodium (DSS)-induced colitis model. Colitis was induced in mice with 3% DSS. The therapeutic effects of TENVs were evaluated using histopathology, inflammatory cytokine profiling, intestinal barrier assessment, and immunofluorescence (IF) analysis. Potential mechanisms were investigated by RNA-seq, Western blotting, 16S rDNA sequencing, and fecal microbiota transplantation (FMT). TENVs showed typical nanovesicular morphology and remained stable in simulated gastric and intestinal fluids. Oral treatment with TENVs markedly attenuated DSS-induced colitis. Mice showed improved clinical indices, less histological damage, and better-preserved epithelial barrier integrity, together with reduced macrophage activation, colonic MPO and IL-17A expression, and circulating pro-inflammatory cytokines. Transcriptomic profiling and immunoblotting revealed changes consistent with attenuation of IL-17/MAPK-associated inflammatory signaling. TENVs also reshaped the gut microbiota. FMT from donors receiving TENVs alleviated colitis in recipient mice. TENVs act on multiple pathological processes in DSS-induced colitis. Their combined effects on mucosal inflammation, epithelial barrier integrity, IL-17/MAPK-associated inflammatory signaling, and the gut microbiota may jointly contribute to the observed protection.