Chinese researchers develop glucose-responsive oral probiotics for diabetes

A research team led by Professor Ye Haifeng from East China Normal University has developed an engineered probiotic, named GIFT, designed to treat diabetes by sensing glucose levels and responding accordingly. The study, published in the journal Nature, details how these oral probiotics use a synthetic gene circuit to automatically produce GLP-1 (glucagon-like peptide-1) analogues, such as semaglutide, based on the body's real-time glucose concentration.

Using Escherichia coli Nissle 1917 as a chassis, the GIFT system utilizes a glucose-sensing protein called HexR to act as a molecular switch. When glucose levels rise, the switch activates the production of GLP-1; when levels normalize, production ceases. This autonomous, demand-based synthesis aims to mitigate common side effects associated with long-term, high-dose semaglutide use, such as thyroid issues and gastrointestinal distress.

In animal trials, the probiotics demonstrated significant efficacy and safety. In mice, continuous oral administration improved fasting blood glucose, glucose tolerance, and insulin sensitivity while reducing liver and kidney damage. In tests involving cynomolgus monkeys with type 2 diabetes, oral GIFT administration maintained stable blood glucose levels over a five-week period without observed inflammatory or toxic reactions.