A engineered Bifidobacterium longum secreting a bioative penetratin-Glucagon-like peptide 1 fusion protein enhances Glucagon-like peptide 1 absorption in the intestine.

Glucagon-like peptide-1 (GLP-1) is an incretin-derived hormone secreted by intestinal L-cells in response to nutrient ingestion. It improves pancreatic function and it is considered to have a potential role in treatment of type 2 diabetes. However, its short half-life limits its therapeutic applications. Here, to circumvent this problem, we engineered Bifidobacterium longum, a bacterium naturally occurring in the intestinal flora, to express a secreted and biologically active form of the human GLP-1. Our data showed that the bacteria secreted our penetratin-GLP-1fusion protein successfully. The penetratin-GLP-1 fusion protein was a fully functional GLP-1 and displayed enhanced absorption significantly (P<0.001) in the colon. This work is the first report of an expressed penetratin-GLP-1 fusion protein in bifidobacteria and lays the foundation for the use of GLP-1-based treatment of type 2 diabetes in the future.