Abstract
<title>Abstract</title> <p> Current therapies of inflammatory bowel disease (IBD) predominantly target single inflammatory pathways and often fail to resolve oxidative stress or restore mucosal homeostasis, resulting in suboptimal clinical outcomes. Here, we report a biomimetic nano-biohybrid platform that integrates multifunctional nanozymes with probiotic-derived extracellular vesicles for synergistic treatment of IBD. In this system, a Cu/Zn bimetallic nanozyme with superoxide dismutase- and catalase-mimetic activities is engineered to achieve efficient reactive oxygen species (ROS) scavenging, while extracellular vesicles derived from <italic>Faecalibacterium prausnitzii</italic> provide intrinsic intestinal targeting, mucus penetration capability, and immunomodulatory bioactivity. Thus, in a colitis model, the hybrid system markedly alleviates disease severity, as evidenced by improved body weight recovery, reduced disease activity index (DAI), and restoration of colon length. In addition, this treatment significantly suppresses ROS accumulation, downregulates pro-inflammatory cytokines, and promotes epithelial barrier repair by upregulating tight junction proteins. These results indicated that our work establishes a multifunctional therapeutic strategy that integrates nanocatalytic ROS regulation with microbiota-derived biological signaling, providing a promising platform for precision intervention in IBD and other inflammation-associated diseases. </p>