Engineered Living Glues for Autonomous Detection and On-Demand Treatment of Inflammatory Bowel Disease

Abstract Smart biomaterials capable of autonomously sensing pathological conditions and executing targeted medical interventions offer therapeutic advantages over conventional passive biomaterials. However, their development remains a considerable challenge. Here, we introduce a therapeutic “living glue” for the automatic detection and on-demand treatment of inflammatory bowel disease (IBD). This living glue employs a genetically engineered, non-pathogenic Escherichia coli with a highly sensitive blood-inducible gene circuit to monitor gastrointestinal bleeding, a key indicator of severe IBD. Upon detection, the bacteria respond by producing potent adhesive and therapeutic proteins around bleeding sites, enabling robust attachment to inflamed tissues and sustained treatment. In a dextran sulfate sodium (DSS)-induced mouse model, a single rectal administration of the living glue markedly improved weight recovery, reversed colonic shortening, and reduced intestinal bleeding. Additionally, the living glue decreased intestinal inflammation, promoted mucosal repair, and restored gut barrier integrity, demonstrating comprehensive therapeutic effects in alleviating IBD symptoms. This study highlights the potential of integrating programmable, living components into biomaterials for autonomous, targeted, and enhanced medical interventions.