Researchers at the Shanghai Academy of Natural Sciences have developed an orally administered living drug composed of engineered probiotic bacteria capable of sensing elevated blood glucose and automatically releasing GLP-1, a hormone that stimulates insulin secretion, in response. The study, published in Nature, represents a proof-of-concept for glucose-responsive, self-regulating diabetes therapy.
The system, termed GIFT, is built on Escherichia coli Nissle 1917, a well-characterised probiotic gut bacterium. The researchers introduced a synthetic gene circuit controlled by a sensor protein called HexR. In the absence of glucose, HexR suppresses therapeutic gene activity. When glucose enters the bacteria, cellular metabolism converts it into a molecule called KDPG, which binds to HexR and releases the promoter, triggering GLP-1 production. Once blood sugar returns to a normal range, hormone production ceases automatically. To extend bacterial survival in the gut, the bacteria were coated with tannic acid and poloxamer 188, prolonging intestinal activity from approximately 8 hours to 36 hours.
In diabetic mice treated daily for 30 days, GIFT reduced fat mass, lowered triglycerides and total cholesterol, improved metabolic markers, and protected liver and kidney function. Unlike semaglutide, which caused lean muscle loss over two months, the probiotic preserved or modestly increased lean muscle mass. When combined with insulin, the probiotic also appeared to reduce hypoglycaemia risk compared with semaglutide.
In spontaneously diabetic monkeys, a single oral dose maintained blood glucose control for up to three days and improved insulin levels, an important step given the genetic proximity of non-human primates to humans.
The authors note that clinical translation will require safety trials, stability testing, and regulatory assessment given the genetically modified nature of the organism.
Source: Guan N et al. Glucose-responsive probiotics for glycaemic modulation in mice and monkeys. Nature (2026). DOI: 10.1038/s41586-026-10909-6
