Engineered Gut Bacteria Could Deliver GLP-1 'On Demand' for Diabetes, Early Animal Trials Suggest

Researchers at East China Normal University in Shanghai have engineered a strain of E. coli bacteria to sense blood glucose levels and release the hormone GLP-1 only when needed, in early animal trials described in a paper published in Nature. GLP-1, or glucagon-like peptide 1, is the hormone mimicked by diabetes and weight-loss drugs such as Ozempic and Wegovy.

The team inserted a glucose-responsive regulator gene into the bacteria, creating a "glucose-sensing and functional response probiotic" (GIFT). Delivered as an oral pill, the living bacteria activate only when blood glucose rises, in principle avoiding the risk of receiving needlessly high doses that can come with a fixed daily injection. "Our probiotics-based living drug enables therapeutic dosing in response to real-time blood glucose levels," the researchers wrote, describing it as "a programmable, orally deliverable sense-and-respond platform for metabolic therapy without transplantation."

In people with type 2 diabetes, cells become resistant to insulin, keeping glucose dangerously high in the blood. Existing GLP-1 drugs raise insulin levels to help overcome that resistance, but a daily dose does not always match the body's minute-by-minute needs. Because GIFT lives in bacteria already suited to the gut, the researchers say it can be given as a pill and avoids the rejection risk associated with other cell-based therapies.

Early trials in mice and diabetic macaques showed the bacteria worked as intended, with no signs of harmful effects, though the researchers caution that human trials are still some way off and further testing is needed to see whether the approach can compete with existing treatments. They said the same platform could potentially be adapted to deliver other blood-sugar-lowering compounds beyond GLP-1.