An oral engineered cerium-peptide composite microsphere inhibits inflammatory bowel disease and reverses chronic fibrosis​​.

Excessive accumulation of reactive oxygen species (ROS) and dysbiosis of the gut microbiota are pivotal contributors to the pathogenesis of inflammatory bowel disease (IBD) and associated fibrosis. In this study, a microfluidic approach was utilized to fabricate a multifunctional therapeutic microsphere system by encapsulating hollow mesoporous cerium oxide nanoparticles (HCeO2) loaded with KP1 short peptides-specific inhibitors of the TGF-β/Smad signaling pathway. The resulting composite formulation (KP1@HCeO₂@SAM) was designed to achieve synergistic antioxidant, anti-inflammatory, and antifibrotic effects. The developed microspheres exhibited prolonged intestinal retention and effectively modulated gut microbiota composition, increasing the relative abundance of probiotic species by over sevenfold. Moreover, they demonstrated remarkable reactive oxygen species (ROS) scavenging efficiency (> 95%) and significant inhibition of fibrotic signaling cascades. In dextran sulfate sodium (DSS)-induced murine colitis models, treatment with the microspheres led to a substantial reduction in Disease Activity Index (DAI) (> 76%), restoration of intestinal barrier integrity (> 90%), and mitigation of fibrotic progression, as indicated by a 66% decrease in α-SMA expression. These findings establish a novel and integrative therapeutic platform for the effective management of IBD.