Ulcerative colitis is an agnogenic and refractory intestinal disease. Probiotic therapy has gained prevalence in medical research. Particularly, the probiotic spore coat has shown effectiveness in delivering oral drugs or probiotics for colitis treatment. Nevertheless, challenges persist in understanding the exact mechanism of the spore coat for optimal anti-inflammatory efficacy. Consequently, we develop a type of multifunctional spore coat nanoparticles (CN) derived from probiotic spore coat to comprehensively investigate its mechanisms of action in alleviating inflammation. Surprisingly, our research findings demonstrate that CN exhibits remarkable resistance to the harsh gastric acid environment and possesses the ability to selectively target inflammatory colonic sites characterized by an accumulation of positive charges. Additionally, CN effectively maintains the normal expression levels of zonula-1, occludin, and claudin-1 while simultaneously enhancing the small intestinal mucin 2 to ensure the integrity of intestinal barriers. Furthermore, the metabolomics analysis identifies 88 potential biomarkers that are enriched in three metabolic pathways, including tyrosine metabolism, tryptophan metabolism, and biosynthesis of valine, leucine, and isoleucine. These pathways are associated with Nrf2 signaling pathway activation, NF-kappa B and Nrf2 signaling pathways regulation, and metabolic disorders regulation. Collectively, our work provides a multifunctional nanomaterial CN and elucidates its anti-inflammatory mechanisms for ulcerative colitis treatment.
