Abstract

Our prior studies have indicated that the isinglass polysaccharide derived from Larimichthys crocea (CIP) can enhance the growth of Ligilactobacillus murinus , which may play a significant role in mitigating colitis. This study investigated the potential of Ligilactobacillus murinus and its derived extracellular vesicles (LM-EVs) as therapeutic and prophylactic agents. LM-EVs demonstrated remarkable ameliorative efficacy in colitis models, substantially mitigating colonic injury, atrophy, and hematochezia, coupled with a significant dampening of inflammatory markers. These beneficial effects are underpinned by significant in vitro antioxidant capacity and a favorable initial safety profile, alongside marked immunomodulatory functions. Mechanistically, we propose a significant role for the miR-146a-5p/TRAF6 signaling axis in LM-EV-mediated immunomodulation, specifically its influence on macrophage polarization. Our findings indicate that LM-EVs modulate the expression level of miR-146a-5p within macrophages. miR-146a-5p subsequently targets and suppresses the TRAF6/NF-κB signaling axis, driving macrophage polarization from the M1 to the M2 phenotype, thereby effectively ameliorating colitis. These insights reveal a promising avenue, potentially utilizing probiotic extracellular vesicles for alleviating colitis and paving the way for new frontiers in gut health modulation.