A Nature Biotechnology team engineered nonpathogenic E. coli with a bleeding‑inducible circuit that secretes a barnacle‑derived adhesive protein (CP43K) plus the gut‑healing factor TFF3. In mouse colitis models the bacteria adhered selectively to bleeding mucosa for days after a single administration, reduced intestinal inflammation, promoted mucosal repair and improved clinical endpoints. The approach couples autonomous sensing of a pathological cue (gastrointestinal bleeding) to localized, sustained therapeutic delivery—addressing the challenge of maintaining activity at inflamed sites. Data include two models of IBD (DSS colitis and IL‑10 knockout) with weight recovery and reduced bleeding reported. Authors discuss translational hurdles—biosafety, containment, and regulatory pathways—but position the work as a proof‑of‑concept for programmed living therapeutics that target dynamic disease signals.