A yogurt-based treatment for diabetes that uses non-harmful bacteria is being tested on diabetic mice. Gut microbes that have been engineered to make a specific protein are helping regulate blood sugar in the rodents, according to research presented at the American Chemical Society conference in Washington, D.C. Scientists hope the treatment might one day provide an alternative for people with diabetes.
The research, which is still in its early stages, represents a new take on age-old supplements – probiotics – which are composed of non-harmful bacteria. Often found in yogurt, these live microorganisms are ingested to promote health. New understanding of these microbes is allowing them to be engineered to help alleviate specific ailments such as diabetes, cholera and even tooth decay.
"The concept of using bacteria to help perform (or fix) human disorders is extremely creative and interesting," said Kelvin Lee, a chemical engineer at the University of Delaware, in Maryland. "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, commenting on the research.
People with type 1 diabetes can’t make insulin, a hormone that triggers muscle and liver cells to take up glucose and store it for energy. By using the existing signaling system between the epithelial cells lining the intestine and the millions of healthy bacteria that normally reside in the gut, biochemical engineer John March and his team at Cornell University re-created this missing circuit. 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 produces the protein 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 GLP-1 could trigger human intestinal cells in a dish to produce insulin in response to glucose (though it's not yet clear why the protein has this effect).
In the new research, scientists fed the bacteria to diabetic mice. "After 80 days, the mice [went] from being diabetic to having normal glucose blood levels," says March. "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.
March says creating bacteria that produce the protein has a number of advantages over using the protein itself as the treatment. "The bacteria can secrete just the right amount of the protein in response to conditions in the host," says March. That could ultimately "minimize the need for self-monitoring and allow the patient's own cells (or the cells of the commensal E. coli) to provide the appropriate amount of insulin when needed," observes Cynthia Collins, a bioengineer at Rensselaer Polytechnic Institute, in Troy, NY.
Protein-based drugs can be very expensive to make and often strike problems as they degrade during digestion. “Probiotics are cheap - less than a dollar per dose," added March. This is especially helpful in third world countries where cheaper delivery methods of treatment (yogurt) could be easily distributed throughout villages, etc.
The researchers don't know exactly how or where the diabetic mice are producing insulin or if the treatment has any harmful effects. "The mice seem to have normal blood glucose levels at this point, and their weight is normal," says March. "If they stopped eating, we would be concerned."
March's microbes are just one of a number of new strains being developed to treat disease, including bacteria designed to fight cavities, produce vitamins and treat lactose intolerance. His group is also engineering a strain of E. coli to prevent cholera. Cholera prevention "needs to be something cheap and easy and readily passed from village to village, so why not use something that can be mixed in with food and grown for free?" says March.
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