Barnacle gloop could improve inflammatory bowel disease treatments


Inflammatory bowel disease can cause bleeding sores
SPRINGER MEDIZIN/SCIENCE PHOTO LIBRARY
Scientists seeking relief for people with inflammatory bowel disease have turned to an unusual source of inspiration: barnacles.
Inflammatory bowel diseases (IBD), such as Crohn’s disease and ulcerative colitis, appear to occur when a person’s immune system attacks their gut, leaving it inflamed. Its main symptoms are diarrhea, severe abdominal pain, weight loss and intestinal bleeding in the stool.
Anti-inflammatory medications, such as steroids, can relieve symptoms. But if the bleeding persists, doctors can use small metal clamps inserted into the intestine via the anus to close the wounds caused by the inflammation. However, this carries a risk of infection and can even make sores worse.
Looking for a gentler approach, scientists have previously genetically engineered bacteria to produce substances that help heal wounds. However, these microbes are usually cleared from the gut within a few days and must be activated manually using drugs, says Bolin An of the Shenzhen Institute of Synthetic Biology in China.
Now, An and his colleagues have genetically modified a harmless strain of Escherichia coli bacteria to produce a protein fragment that promotes wound healing when detecting blood. Importantly, bacteria also make certain types of “cement proteins,” which barnacles use to attach themselves to underwater surfaces. Based on tests in laboratory dishes, the team hoped that these proteins would act as an anti-inflammatory seal against bleeding wounds, calling them “living glue.”
To test it, researchers used a toxic chemical to cause IBD-like problems — including intestinal inflammation and injury, leading to weight loss — in mice. Each mouse then received either a single dose of a harmless strain of E.colithe genetically modified product E.coli or saline solution, all administered to the intestine via a tube passing through the anus.
Ten days later, the mice having received the modified bacteria, still present in their intestines, regained most of the weight lost. Unlike the other two groups, their intestines even resembled those of healthy mice. None of the mice showed signs of side effects.
The team also saw similar effects when mice were given a pill containing the bacteria, suggesting that this approach could one day be administered orally in humans. “It’s really promising and a novel approach,” says Shaji Sebastian of the University of Hull in the United Kingdom. Intestinal wound healing and inflammation in mice is quite similar to that in humans, although testing in humans is needed, he says.
Researchers now plan to test this approach in larger animals, including pigs, in part to determine how long the engineered bacteria can be retained in the gut, An says. But it could take up to 10 years before it reaches clinics, because more testing is needed to show that not only does it work, but it also offers benefits over existing treatments in humans, Sebastian says.
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