Biomarker-responsive engineered probiotic diagnoses, records, and ameliorates inflammatory bowel disease in mice

Rapid advances in synthetic biology have fueled interest in engineered microorganisms that can diagnose and treat disease. However, designing bacteria that detect dynamic disease-associated biomarkers that then drive treatment remains difficult. Here, we have developed an engineered probiotic that noninvasively monitors and records inflammatory bowel disease (IBD) occurrence and progression in real time and can release treatments via a self-tunable mechanism in response to these biomarkers. These intelligent respon-sive bacteria for diagnosis and therapy (i-ROBOT) consists of E. coli Nissle 1917 that responds to levels of the inflammatory marker thiosulfate by activating a base-editing system to generate a heritable genomic DNA sequence as well as producing a colorimetric signal. Fluctuations in thiosulfate also drive the tunable release of the immunomodulator AvCystatin. Orally administering i-ROBOT to mice with colitis generated molecular recording signals in processed fecal and colon samples and effectively ameliorated disease. i-ROBOT provides a promising paradigm for gastrointestinal and other metabolic disorders.

Automated summary

Engineered probiotic i-ROBOT has been developed to noninvasively monitor and record the occurrence and progression of inflammatory bowel disease (IBD) in real time, and release treatments based on disease-associated biomarkers. It provides a heritable genomic DNA sequence and a colorimetric signal by activating a base-editing system in response to the inflammatory marker thiosulfate. In experiments with mice, i-ROBOT effectively ameliorated colitis and showed potential for the treatment of gastrointestinal and metabolic disorders.