Colon-targeted alginate/chitosan microspheres for co-delivery of synbiotics and nanozymes ameliorate inflammatory bowel disease.

Inflammatory bowel disease (IBD) is closely associated with gut dysbiosis and immune imbalance. Synbiotics, combining probiotics and prebiotics, represent a promising dietary strategy; however, their therapeutic efficacy is often limited by poor gastrointestinal stability and insufficient colon delivery. In this study, we developed a colon-targeted delivery system based on alginate/chitosan microspheres for the co-delivery of L. acidophilus, prebiotic stachyose, and a redox-active component. The formulated system exhibited excellent stability under simulated gastrointestinal conditions and effectively preserved probiotic viability. In dextran sulfate sodium (DSS)-induced colitis models, oral administration significantly alleviated disease symptoms, including body weight loss, colon shortening, and histological damage. Mechanistically, treatment restored gut microbial diversity and composition, characterized by enrichment of beneficial genera (e.g., Lactobacillus and Akkermansia) and suppression of opportunistic pathogens. Notably, synbiotic delivery markedly enhanced short-chain fatty acid (SCFA) production, including acetate, propionate, and butyrate, accompanied by upregulation of SCFA receptor expression. These changes were associated with improved intestinal redox status and rebalanced immune responses, as evidenced by increased regulatory T cells and reduced pro-inflammatory Th17 cells. Collectively, this study demonstrates that colon-targeted synbiotic delivery effectively remodels the gut microbiota and metabolic microenvironment, offering a promising food-derived strategy for IBD management.