Foodborne fungus may disrupt gut healing in Crohn’s disease

• A usually harmless fungus found in cheese, sausage, beer, wine, and other fermented foods may prevent intestinal ulcers from healing in people with Crohn’s disease.
• The researchers behind the new study say their evidence is preliminary, so it is too soon to recommend dietary changes.
• Antibiotic treatments in people may disrupt friendly gut bacteria, allowing the fungi to thrive.
• If scientists can develop an oral antifungal, it could improve intestinal wound healing and reduce symptoms.

Crohn’s disease is a type of inflammatory bowel disease that causes chronic inflammation of the gut, mainly in the small intestine.

The National Institute of Diabetes and Digestive and Kidney Diseases report that more than half a million people in the United States have the condition.

In people with Crohn’s disease, minor injuries to the gut lining fail to heal properly. These ulcers cause abdominal pain, bleeding, and diarrhea, among other symptoms.

Researchers have now discovered that a common foodborne fungus colonizes the intestinal wounds in a mouse model of the disease and in humans.

Once established, the microbe appears to enhance inflammation and slow down wound healing.

The research, led by scientists at Washington University School of Medicine in St. Louis, MO, and the Cleveland Clinic, OH, has been published in the journal Science.

Exploiting a weakness

The fungus is a type of yeast called Debaryomyces hansenii that is often found in:

• cheese
• sausage and other processed meats
• beer and wine
• fermented foods

The fungus is harmless to people who are otherwise healthy, but it exploits a weakness in the intestinal lining of people with Crohn’s disease to penetrate the tissue.

First author Dr. Umang Jain, an instructor in pathology and immunology at the School of Medicine, explains:

“If you look at stool samples from healthy people, this fungus is highly abundant. 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.”

Dr. Jain emphasizes that the research is preliminary and that patients should not stop eating cheese or processed meat.

His team is planning a larger study to investigate whether a person’s diet helps determine the abundance of the fungus in their intestine.

“If so, it is possible dietary modulation could lower levels of the fungus and thereby reduce symptoms of Crohn’s disease,” he says.

Sites of injury

To discover what impairs wound healing in the guts of people with Crohn’s disease, Dr. Jain and his colleagues studied mice with injured intestines.

When they sequenced microbial DNA in the animals’ gut, this revealed that D. hansenii was particularly abundant at the sites of injury.

To investigate whether the same is true of humans, the researchers compared biopsies from the intestines of seven people with Crohn’s disease with biopsies from 10 healthy people.

While the gut tissue of all seven people with the condition contained the fungus, only one of the healthy individuals harbored it.

Next, the researchers compared tissue samples from inflamed and uninflamed areas in the guts of 10 people with Crohn’s disease. This showed that the fungus had only colonized sites of injury and inflammation.

While these results are strong evidence that the fungus colonizes inflamed areas, they do not prove that it is responsible for impairing wound healing.

To investigate whether there is a causal link, the scientists grew cultures of D. hansenii from the guts of injured mice and people in the lab.

When they later introduced these fungi into the injured intestines of antibiotic-treated, microbe-free mice, the fungi colonized their wounds and slowed down healing.

Treating the mice with an antifungal drug called amphotericin B — which eliminated the fungus — accelerated healing.

Unintended consequence

In a comment article accompanying the paper, Tyson Chiaro and Dr. June L. Round from the University of Utah School of Medicine in Salt Lake City note that friendly bacteria are known to promote healing of the gut lining.

However, doctors often treat Crohn’s disease with antibiotics, which can disrupt these beneficial bacterial species.

The authors say this may have the unintended consequence of exacerbating inflammation by allowing fungi to colonize parts of the gut lining formerly dominated by bacteria.

While the new study found that amphotericin B could help heal ulcers in the intestines of people with Crohn’s disease, the antifungal is not widely used in people, because it must be injected into the bloodstream.

Dr. Jain and his colleagues are working with chemists to develop an oral antifungal.

A new treatment and possibly dietary changes could one day improve Crohn’s disease symptoms by speeding up wound healing.

It would not be a cure, however, because inflammation would still be present.

“But in people with Crohn’s [disease], impaired wound healing causes a lot of suffering,” says Dr. Jain. “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 have not been able to do with more traditional approaches.”

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