In a new study titled “Debaryomyces is enriched in Crohn’s disease intestinal tissue and impairs healing in mice” published in the journal Science, researchers at Washington University School of Medicine in St. Louis and the Cleveland Clinic have discovered that a salt-tolerant fungus Debaryomyces hansenii, used in the food industry for surface ripening of cheese and meat products, latches on to injured and inflamed regions in the guts of patients with Crohn’s disease, causing wounds to fester, abdominal pain, bleeding, diarrhea and other unpleasant symptoms.
The researchers also show, treating infected model mice with antifungal medication eliminates the fungus and allows the wounds to heal, suggesting antifungal drugs and dietary changes targeted to reduce fungal growth in the gut, are potential new therapeutic approaches to improving intestinal wound healing and managing the symptoms of Crohn’s disease.
“We’re not suggesting that people stop eating cheese and processed meat. That would be going far beyond what we know right now,” says Umang Jain, PhD, an instructor in pathology & immunology at the School of Medicine and first author on the study.
“What we know is that this foodborne fungus gets into inflamed, injured tissue and causes harm. We’re planning to perform a larger study in people to figure out if there’s a correlation between diet and the abundance of this fungus in the intestine. If so, it is possible dietary modulation could lower levels of the fungus and thereby reduce symptoms of Crohn’s disease.”
Crohn’s is a chronic inflammatory disease of the digestive tract involving repeated cycles where symptoms flare up and subside. When symptoms flare up, patients’ digestive tracts are speckled with multiple open sores that can persist for weeks or months. Immunosuppressive medications are currently the first course of treatment.
Jain and senior author Thaddeus Stappenbeck, MD, PhD, formerly at Washington University and now at the Cleveland Clinic, use model mice with intestinal injuries to understand why intestinal ulcers take so long to heal in some people. Sequencing microbial DNA at the site of injury, the authors discovered that the fungus Debaryomyces hansenii is abundant in wounds but not in uninjured parts of the intestine.
“People acquire the fungus through their food and drink,” says Jain. D. hansenii is commonly found in all kinds of cheeses, as well as sausage, beer, wine and other fermented foods.
When the authors introduce this fungus into mice with injured intestines, it slows down the healing process. They then eliminate the fungus using an antifungal drug amphotericin B and the healing process speeds up, indicating this fungus plays a role in slowing down wound healing in the gut.
Jain and Stappenbeck examine intestinal biopsies from seven people with Crohn’s disease and ten healthy individuals. All seven patients harbored the fungus in their gut tissue, as compared with only one of the healthy controls.
Tissue sample analysis comparing inflamed and uninflamed regions of the gut in ten Crohn’s patients in a separate analysis, revealed the presence of the fungus in all ten patients was restricted to the inflamed regions.
“If you look at stool samples from healthy people, this fungus is highly abundant,” says Jain. “It goes into your body and comes out again. But people with Crohn’s disease have a defect in the intestinal barrier that enables the fungus to get into the tissue and survive there. And then it makes itself at home in ulcers and sites of inflammation and prevents those areas from healing.”
Amphotericin B was effective in eliminating the fungus in mouse studies but in humans the drug is administered intravenously limiting its use. The researchers are working with chemists to develop an effective antifungal that can be taken by mouth.
“Crohn’s disease is fundamentally an inflammatory disease, so even if we figured out how to improve wound healing, we wouldn’t be curing the disease,” says Jain. “But in people with Crohn’s, impaired wound healing causes a lot of suffering. If we can show that depleting this fungus in people’s bodies—either by dietary changes or with antifungal medications—could improve wound healing, then it may affect the quality of life in ways that we’ve not been able to do with more traditional approaches.”