Engineered Gut Bacteria ‘Talks’ to Other Cells and Fights Disease

Researchers introduced genetically modified bacteria into mice, which reduced glucose and insulin levels in the blood and could become a treatment for diseases like diabetes.

Science has long known that the human gastrointestinal tract operates as a kind of auxiliary central nervous system, communicating with other parts of the body through a chemical language transmitted on the molecular level.

New research suggests this chemical language can be used to treat diseases by sending in genetically engineered bacteria that “talk” to human cells. Given the right circumstances, the modified bacteria can exchange chemical information with the cells and convince them to make metabolic changes that help fight disease.

Scientists at Rockefeller University and the Icahn School of Medicine at Mt. Sinai published research this week demonstrating the new technique in laboratory mice. In a series of experiments, the introduction of modified gut bacteria led to reduced blood-glucose levels and concentrations of insulin, which play a role in the treatment of diseases, including diabetes.

The research, published in the journal Nature, provides new and persuasive evidence that gut bacteria and human cells share a common chemical language. If researchers can achieve fluency in that language, scientists may be able to use genetically modified bacteria to trigger therapeutic changes in the body.

“I believe there is a fundamental need, for healthy human physiology, that the host and its resident bacteria form a stable ecosystem,” co-authors Sean Brady and Louis Cohen said in an email. “To do this requires the ability for bacteria and humans to sense each other through a very simple and perhaps shared chemical language.”

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The key element in this shared chemical language is the presence of organic molecules called ligands, which tend to bind to other, larger molecules. In the gastrointestinal tract, ligands latch onto receptors in the membranes of human cells, leading to specific biological effects, according to the researchers.

The new method developed by Brady and Cohen basically creates artificial ligands by tinkering with the genetics of bacteria in the lab. When these engineered ligands bind with targeted receptors, the cell membrane reacts as if the modified molecules were standard ligands.

A major benefit of the new technique is the genetic material inside the bacteria is much easier to work with than human genes. In fact, all of the genes for all the bacteria inside the human biome have been sequenced at some point, Cohen said. Manipulating the bacterial genes in the lab is therefore simpler, since the scientists have a kind of map from which to work.

Brady and Cohen said the new technique could treat a wide array of ailments.

“There are diseases associated with the microbiome such as inflammatory bowel disease where the therapeutic manipulation of bacterial genes could hold great promise,” they said. “The local delivery of beneficial bacterial metabolites may help to prevent disease flares or promote healing of the intestinal mucosa.”

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In press materials accompanying the research, Cohen argued that even though the engineered bacteria are created in a lab, they shouldn't be thought of as foreign bodies. The body doesn't think so, so neither should we.

“The biggest change in thought in this field over the last 20 years is that our relationship with these bacteria isn't antagonistic,” he said. "They are a part of our physiology. What we're doing is tapping into the native system and manipulating it to our advantage."

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