01 September 2009

Genetically modified bacteria instead of a syringe with insulin

Scientists at Cornell University (Ithaca, New York), working under the leadership of John March, have brought to a new level the use of probiotics - beneficial microorganisms that have been consumed by humans as part of dairy products for centuries. They modified a non-pathogenic strain of E. coli (Escherichia coli) in such a way that yogurt enriched with such bacteria can soon replace insulin injections for diabetic patients.

In type I diabetes, beta cells of the pancreas lose their ability to synthesize the hormone insulin, which triggers the absorption and storage of glucose by muscle and liver cells. The authors decided to try to restore this mechanism with the help of a signaling system used by epithelial cells lining the intestine and beneficial bacteria inhabiting it.

The strain of non-pathogenic E. coli created by scientists synthesizes the GLP–1 protein - a glucagon-like peptide, glucagon-like peptide-1. In a healthy human body, this protein is synthesized by intestinal cells and, among other effects, triggers the production of insulin in the pancreas.

The authors demonstrated that in laboratory conditions, in the presence of glucose, GLP-1 secreting bacteria (dots at the bottom of the image) trigger the synthesis of insulin in human intestinal cell culture (above, highlighted in blue). The mechanisms underlying this phenomenon are not yet clear.

The introduction of new bacteria into the diet of mice with artificially induced diabetes for 80 days reduced the level of glucose in the blood of animals to normal, while in animals of the control group that did not consume bacteria, this indicator remained elevated.

According to the authors, the use of bacteria for the treatment of diabetes has a number of advantages over the use of the GLP-1 protein itself. Bacteria synthesize a certain amount of protein corresponding to the situation in the host body, which minimizes the need for independent monitoring of the body's condition.

Moreover, protein synthesis directly in the body makes it possible to overcome the difficulties associated with the use of protein preparations that are expensive to produce and easily destroyed by the action of digestive juices (the half-life of the active form of GLP–1 is less than two minutes). Probiotics are quite cheap, in addition, if desired, they can be propagated as part of yogurt starter culture.

To date, it is still unclear what exactly is happening in the intestines of animals using new probiotics. Although the animals look completely normal, it is extremely important to exclude the possibility of side effects, such as excessive hormone synthesis or suppression of the normal functioning of intestinal epithelial cells.

In addition to bacteria for the treatment of diabetes, the March group is working on the creation of a number of medicinal strains of microorganisms, including those designed to fight tooth decay, vitamin synthesis, lactose intolerance treatment and cholera prevention.

Despite the initial successes, the authors note that they still have to answer several difficult questions. It is necessary to find out how long modified bacteria can persist in the stomach and how dangerous interference with the intestinal microflora is. In addition, it is known that the composition of the intestinal microflora of different people varies quite a lot and today it is unclear how this can affect the results of bacterial treatment. This factor can be especially critical when selecting optimal individual doses of therapeutic yogurt.

Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of Technology Review

01.09.2009


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