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Biologists manufacture bacteria that may one day treat an unhealthy stomach

Biologists at the Massachusetts Institute of Technology have created a genetically modified version of a common bacteria found in the gut that can sense the environment there and fight disease. And when this designer bacteria works, the proof is in the poop — glowing poop. (In this case, mouse poop.)

We wanted to equip this bacteria with the ability to do new things, like turn on the production of therapeutic molecules or sense disease inside guts, said Timothy Lu, a biologist and senior author on the study. The designer bacteria is modeled after a common gut bacteria called Bacteroides Thetaiotaomicron.

In the past, clinical studies and lab experiments made use of manmade modified bacteria, like E. coli and Listeria, to deliver medicine to treat cancer or obesity. But E. coli and Listeria have a downside. They’re cleared from the body rapidly. Bacteroides thetaiotaomicron is already highly abundant in the human gut, meaning that an altered version of this bacteria designed for therapeutic treatment would last longer within the intestines. This designer bacteria, in other words, could play an important role in drug treatment.

But to monitor whether it was working, Lu’s team had to see the results first.

To do that, they used a technique called bacterial conjugation to insert a gene called luciferase that codes for fluorescence into the gut bacteria’s genome.

“You can turn on genes in the bacterium based on what you feed the mouse,” said Christopher Voigt, a biologist at Massachusetts Institutes of Technology and also a senior author on the study .

Researchers wired the bacteria to switch on when mice chowed down on a plant-based edible starch called arabinogalactan. This starch interacts with a protein that turns on the production of the luciferase gene. Mice fed arabinogalactan had a 75-fold increase in luciferase in their stool. And the more starch the mice were fed, the more the gene turned on, Lu said. In other words, eating starch caused the designer bacteria to produce glowing poop.

Lu’s team also created an off-switch for the bacteria’s glow using CRISPR, a genetic technology that edits DNA. This year, scientists reported that they could edit human embryos using CRISPR, in a bid to possibly tweak genes that cause heritable human diseases.

The end result of the current study, published July 9 in the journal Cell Systems, was that mice with the designer bacteria produced fluorescent poop. Scientists hope this research could eventually help humans with gut diseases like colon cancer or Crohn’s disease.

“You could engineer a Bacteroides to live in the gut and detect when inflammation is just starting, and then flip a switch to turn your poop a certain color, so that you can seek treatment right away,” Lu said.

Or scientists could insert DNA segments into Bacteroides that create therapeutic molecules like aspirin, Lu said.

Some questions remain. Lu’s team would like to invent a signal that would prevent the bacteria from producing too much of a desired gene, which could be harmful. And even though they can turn genes off and on, it’s still unclear how long Bacteroides thetaiotaomicron will stick around in the gut.

Editor’s note: This piece was modified to remove the term, “Frankengut.”

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