The study, published in Diabates, examines the potential benefits of a strain of lactobacillus bacteria that has been engineered to secrete glucagon-like peptide 1 (GLP-1), in aiding blood sugar management.
Led by Professor John March from Cornell University, the research team developed the genetically engineered probiotic strain from a bacterial strain that is commonly found in the human gut, and used a rat model of diabetes to test the potential benefits in controlling blood sugar.
“Diabetic rats fed GLP-1-secreting bacteria showed significant increases in insulin levels and, additionally, were significantly more glucose tolerant than those fed the parent bacterial strain,” reported March and his collegaues. “These rats developed insulin-producing cells within the upper intestine in numbers sufficient to replace 25–33% of the insulin capacity of nondiabetic healthy rats.”
According to the research team behind the study, the findings may put science and industry one step closer to battling diabetes with a human probiotic pill. The technology is licensed by BioPancreate, a wholly-owned subsidiary of Swedish biopharmaceutical firm Cortendo AB - which is working to get the therapy into production for human use.
March and his team engineered a strain of lactobacillus that is commonly found in the human gut to secrete GLP-1 – a hormone that increases the release of insulin and has been shown to stimulate the conversion of both rat and human intestinal epithelial cells into insulin-secreting cells. The GLP-1 secreting probiotic was then given orally to diabetic rats for 90 days, while control rats received the normal lactobacillus strain.
The team found the diabetic rats receiving the engineered probiotic had up to 30% lower incidence of high blood glucose, a hallmark of diabetes. They also reported that upper intestinal epithelial cells in the diabetic rats were converted into cells that acted very much like pancreatic beta cells - which monitor blood glucose levels and secrete insulin as needed to balance glucose levels in healthy individuals.
March explained that the effect this has, is to essentially mimic the blood sugar management role of a healthy, non-diabetic, pancreas.
"The amount of time to reduce glucose levels following a meal is the same as in a normal rat ... and it is matched to the amount of glucose in the blood," he explained – adding that the effect is just as it would be with a normal-functioning pancreas.
"It's moving the centre of glucose control from the pancreas to the upper intestine,” March reiterated.
Though these new intestinal cells replace the insulin capacity in diabetic rats, the team noted that no changes in blood glucose levels were observed when the probiotic was administered to healthy rats.
"If the rat is managing its glucose, it doesn't need more insulin," said March, who added that the current results are that of ‘proof of principle’ research, and future work will test higher doses to see if a complete reversal can be achieved.
Published online ahead of print, doi: 10.2337/db14-0635
“Engineered Commensal Bacteria Reprogram Intestinal Cells Into Glucose-Responsive Insulin-Secreting Cells for the Treatment of Diabetes”
Authors: Franklin F. Duan, Joy H. Liu and John C. March