Mare milk and its extracellular vesicles alleviate DSS-induced colitis in mice by modulating immune responses and reshaping gut microbiota.

Ulcerative colitis (UC) is a chronic inflammatory disorder driven by gut dysbiosis and immune dysfunction. This study evaluated the protective effects of mare milk (MM) and its extracellular vesicles (MM-EVs) in DSS-induced UC. Both interventions alleviated clinical symptoms, restored colonic architecture, and rebalanced mucosal and systemic T-cell immunity. MM preferentially promoted colonic Th17 responses, whereas MM-EVs selectively suppressed Th2 responses, indicating distinct immunomodulatory mechanisms. 16S rRNA sequencing revealed that MM enriched fiber-fermenting taxa, whereas MM-EVs increased butyrate producers alongside certain pro-inflammatory Proteobacteria. Metabolomics showed that MM modulated amino acid and one-carbon metabolism, while MM-EVs affected riboflavin and nucleotide metabolism. Overall, MM and MM-EVs alleviate UC through coordinated regulation of immunity, microbiota, and host metabolism, supporting their potential as functional dietary interventions for UC.