Synthetically engineered probiotic suppresses colorectal cancer via inhibition of Wnt/β-catenin signaling

Recent breakthrough of synthetic biology stimulates the utilization of engineered bacteria for cancer diagnosis and treatment. To achieve the early CRC diagnosis, we performed a comprehensive fecal metabolomic analysis in CRC mice models and patients, and identified ornithine as a specific metabolic biomarker for tumor development.

We subsequently engineered an E. coli Nissle 1917 (EcN)-based bioluminescent (Rluc8) reporter system capable of ornithine-responsive tumor detection. For therapeutic intervention, we constructed a probiotic system that locally releases Dickkopf 3 (DKK3), a potent Wnt signaling antagonist to retard tumor growth. Oral administration of the bacteria demonstrated reduced tumor burden, improved survival outcomes in multiple preclinical models, and the anticancer efficacy was further confirmed in CRC patient-derived organoids.