Inflammatory bowel disease can cause wounds that bleed
SPRINGER MEDIZIN/SCIENCE PHOTO LIBRARY
Scientists looking to provide relief for people with inflammatory bowel disease have turned to an unusual source for inspiration: barnacles.
Inflammatory bowel disease (IBD), such as Crohn’s disease and ulcerative colitis, seems to occur when someone’s immune system attacks their bowel, leaving it inflamed. Its main symptoms are diarrhoea, severe abdominal pain, weight loss and bleeding from the gut into faeces.
Anti-inflammatory drugs, such as steroids, can ease symptoms. But if bleeding persists, doctors may use small metal clips, passed into the gut via the anus, to close wounds caused by the inflammation. However, this carries the risk of infections and can even worsen the wounds.
Searching for a gentler approach, scientists previously genetically engineered bacteria to produce substances that help heal wounds. However, such microbes are typically cleared from the gut within a couple of days, and must be manually activated using drugs, says Bolin An at the Shenzhen Institute of Synthetic Biology in China.
Now, An and his colleagues have genetically engineered a harmless strain of Escherichia coli bacteria to produce a protein fragment that promotes wound healing upon sensing blood. Crucially, the bacteria also make certain types of “cement proteins”, which barnacles use to attach to underwater surfaces. Based on tests in lab dishes, the team hoped these proteins would act like an anti-inflammatory seal against bleeding wounds, calling it a “living glue”.
To put it to the test, the researchers used a toxic chemical to induce IBD-like issues – including inflammation and gut wounds, which led to weight loss – in mice. Each mouse then received either a single dose of a harmless strain of non-engineered E.coli, the genetically engineered E.coli or a saline solution, all of which were delivered to the gut via a tube through the anus.
Ten days later, the mice that received the engineered bacteria, which were still present in their guts, regained most of the weight they had lost. Unlike the other two groups, their guts even resembled those of healthy mice. None of the mice showed signs of experiencing side effects.
The team also saw similar effects when the mice were given a pill containing the bacteria, suggesting that this approach could one day be administered orally in people. “It’s definitely promising and it’s a novel approach,” says Shaji Sebastian at Hull University in the UK. Gut wound healing and inflammation in mice is fairly similar to that in humans, although tests in people are needed, he says.
The researchers now plan to test the approach in larger animals, including pigs, partly to determine how long the engineered bacteria can be retained within the gut, says An. But it could be up to 10 years before it reaches clinics, because so much testing is needed to show that it not only works, but also provides benefits over existing treatments in people, says Sebastian.
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