A common yeast used in food processing may exacerbate the effects of Crohn's disease by weakening the colon's healing process.
A study published March 11 in Science suggests that the fungus can infiltrate protective areas in the colon lining. The study is the first to present compelling evidence that there may be an infectious element to the chronic inflammatory bowel disease, which has no cure.
An estimated half-million Americans live with Crohn's disease, according to the National Institutes of Health, and Crohn's has become more common for unknown reasons. Symptoms include diarrhea, weight loss and abdominal cramping and pain.
For the study, researchers examined intestinal biopsy wounds of lab mice previously treated with antibiotics, and investigated why their wounds were not healing properly. The researchers suspected the presence of a fungus, and were able to treat the improper healing with a broad-spectrum antifungal drug.
This treatment alone confirmed that a fungus was likely to blame, but it did not identify which one. So the researchers proceeded to sequence the microorganisms inside each mouse gut, revealing a robust myriad of fungi. But they still did not find the culprit until they looked at the wounds themselves.
"That's when we knew we had something really good," corresponding author Thaddeus Stappenbeck, chair of the Cleveland Clinic's Lerner Research Institute, told The Academic Times. "We did this experiment 10 different ways in all different kinds of mice. We got the same exact result every single time: If there was impaired healing, the only fungus that got into the wound bed was Debaryomyces hansenii."
D. hansenii is already known by food manufacturers as a hardy fungus. It is renowned for its ability to withstand the high heat and high salinity of meat and cheese processing, along with winemaking, and is consumed by millions of people every day. Its resilience may allow it to thrive in the guts of mice and humans, according to Stappenbeck.
Because this yeast was so active inside the wounds of lab mice, the researchers hypothesized that it may be found in the intestinal ulcers of Crohn's disease patients as well. To test this hypothesis, they removed inflamed pieces of tissue from the colons of Crohn's disease patients undergoing colonoscopy, and found D. hansenii there, too.
"Crohn's disease is a miserable disease, and very hard to treat," said Stappenbeck. "We know from previous studies that there are a lot of fungi in the gut, but no one has known exactly where the pathogenic bug really is."
While this research does not prove exactly how D. hansenii exacerbates Crohn's disease, the yeast may be infiltrating the pockets of stem cell-producing areas that line the colon and protect the body from the bacteria, viruses and fungi found within. These areas are known as crypts, and are typically very resilient themselves. Stappenbeck compared them to a line of egg cartons forming a barrier, where a few bare spots can compromise an entire area and lead to infection.
"There are certain injuries, like in Crohn's disease, where the inflammation damages and eliminates certain crypts, and you have to have a mechanism to replace them," said Stappenbeck. "That's also been a mystery: Why some patients don't replace crypts very well. This is a potential explanation. This infection seems to inhabit this process of reassembling crypts."
Crohn's has long been considered an immune disorder, possibly resulting from the body overreacting to microorganisms found inside the intestines.
Prior research from the 1980s and '90s, now largely discredited, tried to link Crohn's to a bacteria related to tuberculosis, according to Stappenbeck.
"What's exciting about this work is that it at least opens the door to the idea that there may be an infectious component to the disease that propagates it," said Stappenbeck. "And if it is an infectious disease, you don't want to inhibit the immune system — you want to do something to remove the infectious agent."
The research may lead to greater use of antifungal treatments in the future, but this doesn't necessarily mean that Crohn's patients should start asking their doctor for antifungal medications. Stappenbeck would like to see these results replicated elsewhere first. Also, antifungal treatments tend to have "some toxicity," he said, and it would be best to determine if the patient actually has the infection before prescribing anything.
A quick, easy way to do that is with a blood test, which is currently being developed. Stappenbeck also plans to expand this research to include children and Crohn's patients outside the U.S.
The study, "Debaryomyces is enriched in Crohn's disease intestinal tissue and impairs healing in mice," published March 11 in Science, was authored by Umang Jain, Aaron M. Ver Heul, Shanshan Xiong, Martin H. Gregory, Justin T. Kern, Derek A. G. Barisas, J. Steven Leal-Ekman, Parakkal Deepak, Matthew A. Ciorba and Ta-Chiang Liu, Washington University in St. Louis; Elora G. Demers and Deborah A. Hogan, Dartmouth University; Chin-Wen Lai, Washington University in St. Louis and Agmen Inc.; Brian D. Muegge, Washington University in St. Louis and VA Medical Center, St. Louis; Philip Debbas, Jonathan Braun, Dermot P. B. McGovern and David M. Underhill, Cedars-Sinai Medical Center, Los Angeles; and Thaddeus Stappenbeck, Washington University in St. Louis and Cleveland Clinic.