Friendly gut microbes that have been engineered to make a specific protein can help regulate blood sugar in diabetic mice, according to preliminary research presented last week at the American Chemical Society conference in Washington, D.C. While the research is still in the very early stages, the microbes, which could be grown in yogurt, might one day provide an alternative treatment for people with diabetes.
The research represents a new take on probiotics: age-old supplements composed of nonharmful bacteria, such as those found in yogurt, that are ingested to promote health. Thanks to a growing understanding of these microbes, a handful of scientists are attempting to engineer them to alleviate specific ailments. “The concept of using bacteria to help perform (or fix) human disorders is extremely creative and interesting,” wrote Kelvin Lee, a chemical engineer at the University of Delaware, in Maryland, in an e-mail. “Even if it does not directly lead to a solution to the question of diabetes, it opens up new avenues of thought in a more general sense,” says Lee, who was not involved in the research.
People with type 1 diabetes lack the ability to make insulin, a hormone that triggers muscle and liver cells to take up glucose and store it for energy. John March, a biochemical engineer at Cornell University, in Ithaca, NY, and his collaborators decided to re-create this essential circuit using the existing signaling system between the epithelial cells lining the intestine and the millions of healthy bacteria that normally reside in the gut. These epithelial cells absorb nutrients from food, protect tissue from harmful bacteria, and listen for molecular signals from helpful bacteria. “If they are already signaling to one another, why not signal something we want?” asks March.
The researchers created a strain of nonpathogenic E. coli bacteria that produce a protein called GLP-1. In healthy people, this protein triggers cells in the pancreas to make insulin. Last year, March and his collaborators showed that engineered bacterial cells secreting the protein could trigger human intestinal cells in a dish to produce insulin in response to glucose. (It’s not yet clear why the protein has this effect.)
In the new research, researchers fed the bacteria to diabetic mice. “After 80 days, the mice [went] from being diabetic to having normal glucose blood levels,” says March. Diabetic mice that were not fed the engineered bacteria still had high blood sugar levels. “The promise, in short, is that a diabetic could eat yogurt or drink a smoothie as glucose-responsive insulin therapy rather than relying on insulin injections,” says Kristala Jones Prather, a biochemical engineer at MIT, who was not involved in the research.