A recent study entitled “Engineered Commensal Bacteria Reprogram Intestinal Cells Into Glucose-Responsive Insulin-Secreting Cells for the Treatment of Diabetes” reveals that an engineered a strain of Lactobacillus producing GLP-1 can promote insulin secretion from intestinal cells and lower hyperglycemia in diabetic rats. The study was published in the journal Diabetes.
A strategy to treat diabetes has focused on reprogramming non-pancreatic β cells into insulin-producing cells. This has been pursued in vitro, but more recently researchers have tried to reprogram cells in vivo by inducing non insulin producing pancreatic cells or even other tissue specific cells, such as rat intestinal epithelial cells, into β cells. This was discovered to be possible with a single factor, the full-length form of glucagon-like peptide-1 (GLP-1), a 30-amino acid peptide hormone produced in the intestinal epithelial endocrine L-cells that increases insulin secretion from the pancreas. However, the same study highlighted that delivering GLP-1 to intestinal cells, either by injection or surgery, proved difficult. Other strategies to deliver bioactive compounds such as GLP-1 were necessary. A subsequent suggested method involved using intestinal commensal bacteria in the gut that, because they have already established a line of communication with intestinal cells, are more efficient and avoid the degradation observed with other methods.
In this study, a team of researchers at Cornell University in Ithaca, NY investigated a new method of delivery by oral administration of human commensal bacteria, specifically Lactobacillus, a common gut probiotic, which were engineered to secrete GLP-1. The authors determined whether this route of administration resulted in an improvement of hyperglycemia of diabetic rats by GLP-1 targeting intestinal cells and reprogramming the cells to secrete insulin. Rats were given engineered Lactobacillus over 90 days and the authors observed that this resulted in a 30 percent decrease of blood hyperglycemia. The team’s present goal is to determine whether higher doses of engineered Lactobacillus can be administered with better outcomes. Notably, the treatment indeed resulted in a reprogramming of intestinal epithelial cells into functional insulin-secreting cells.
John March, professor of biological and environmental engineering at Cornell University and the study’s lead author commented in a press release, “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. It’s moving the center of glucose control from the pancreas to the upper intestine.”
The strategy was licensed by BioPancreate, a subsidiary of biopharmaceutical company Cortendo AB, currently focused on testing the translation of these findings into human application.