Orchestrating Gut Disorders by Oral Delivery of a Living–Synthetic Hybrid Hydrogel

Elevated intestinal inflammation, reactive oxygen species (ROS), and gut microbiota dysbiosis are prominent features of various intestinal disorders. In this work, we develop an oral inulin-based hydrogel delivery system (LICH) containing living probiotics and hyaluronic acid (HA)-modified carbon dot (CD) nanoenzymes to orchestrate gut disorders. Utilizing the hydrophobic properties of HA under acidic conditions, LICH contracts its network to safeguard probiotics during gastric transit. Upon reaching the intestine, HA-modified CD enables spatiotemporal targeting of lesion sites, achieving anti-inflammatory and ROS-scavenging effects. Concurrently, probiotics and inulin synergistically restore a balanced gut microbiota. In a murine model of ulcerative colitis, LICH exhibits prolonged intestinal retention and significantly ameliorates the pathological microenvironment. Transcriptomic and metabolomic analyses further reveal that LICH exerts its therapeutic effects primarily by modulating inflammation, scavenging ROS, and promoting intestinal barrier repair. This study provides a versatile oral platform to regulate multifaceted pathological characteristics for the treatment of intestinal disorders.