Biochemotaxis‐Oriented Engineering Bacteria Expressing GLP‐1 Enhance Diabetes Therapy by Regulating the Balance of Immune

Abstract Glucagon like peptide‐1 (GLP‐1) is an effective hypoglycemic drug that can repair the pancreas β cells and promote insulin secretion. However, GLP‐1 has poor stability and lacks of target ability, which makes it difficult to reach the site of action to exert its efficacy. Here, GLP‐1‐expressing plasmids are introduced into the Escherichia coli Nissle 1917 (EcN) and a lipid membrane is formed through simple self‐assembly on its surface, resulting in an oral delivery system (LEG) capable of resisting the harsh environment of the gastrointestinal tract. The system utilizes the chemotactic properties of probiotics to achieve efficient enrichment at the pancreatic site, and protects islet β cells from destruction by regulating the balance of immune cells. More interestingly, LEG not only continuously produces GLP‐1 to restore pancreatic islet β cell function and secrete insulin to control blood sugar levels, but also regulates the intestinal flora and increases the richness and diversity of probiotics. In mice diabetes models, oral administration of LEG only once every other day has good biosafety and compliance, and achieves long‐term control of blood glucose. Therefore, this strategy not only provides an oral delivery platform for pancreatic targeting, but also opens up new avenues for reversing diabetes.