Bioengineered Escherichia coli Nissle 1917 with ROS tolerance modulates gut microbiota-host metabolic axis to ameliorate type 2 diabetes

Wwe report a synthetically bioengineered probiotics consortium developed through directed metabolic adaptations of Escherichia coli Nissle 1917 (EcN) under iterative hydrogen peroxide selection, subsequently functionalized with fructooligosaccharide-calcium carbonate composites. REcN-F/Ca exhibited enhanced reactive oxygen species tolerance through upregulated antioxidant enzymes and hydrogen sulfide-mediated redox balancing, alongside improved gastrointestinal survivability. In high-fat diet-induced obese mice, REcN-F/Ca restored gut microbiota diversity, enriched butyrogenic taxa (Lachnospiraceae and Blautia), and rescued short-chain fatty acids depletion. Transcriptomic profiling revealed PPAR signaling activation, driving lipid metabolism and suppressing adipose inflammation. These effects translated to systemic metabolic improvements with attenuated weight gain, restored glucose homeostasis, and reduced insulin resistance in the obesity and T2DM murine model. Our findings establish REcN-F/Ca as a synthetically engineered probiotics that simultaneously corrects intestinal ecological perturbations and reverses host metabolic dysfunction, proposing a novel pharmacomicrobiomics paradigm for metabolic syndrome management.