Allen decided to consult with Stappenbeck, an expert in IBD.
"I've looked at quite a few proposed mouse models of IBD, and I recognized right away that this had the potential to be outstanding," says Stappenbeck. "The colons of the mice were incredible. They were filled with inflammatory T cells. We found the mice almost exactly replicated the most acute types of ulcerative colitis."
Unlike prior models of IBD, the mice consistently develop gastrointestinal problems within a short time period and at a predictable point in their lifespan. When researchers treated the mice at three weeks with the antibiotics ciprofloxacin and metronidazole, colon inflammation was reduced and the mice were able to gain weight and survive longer.
Scientists believe IBD results from the host immune system damaging the tissues of the gut while erroneously attacking food and gut microorganisms that aid food digestion. There are an estimated 500 different species of microbes living in the gut, so sorting out which species are being attacked by the immune system has been an imposing challenge.
The new model may significantly ease that challenge. Although the dual antibiotics used to treat the mice are broad-spectrum, they didn't sterilize the guts of the mice, suggesting that the treatment happened to eliminate the microorganisms causing IBD.
"We'd like to treat the mice and then reintroduce candidate microorganisms into their guts to see if this restarts the inflammatory reaction," says Stappenbeck.
Stappenbeck and Allen plan continued collaborative study of the model.
|Contact: Michael C. Purdy|
Washington University in St. Louis