The human gut is crawling with bacteria, but a new study suggests these microbes are not alone: Mammal intestines are also home to at least 100 distinct types of fungi.
Although these fungi generally help maintain gut health, the new research in mice suggests an overgrowth of fungi worsens inflammatory bowel diseases, such as colitis and Crohn’s disease, by increasing inflammation in the intestines. Further, the findings suggest anti-fungal drugs may have a role in treating these incurable diseases.
"We’re not sure if it’s the levels or the types of fungi that might matter, or the genetic predisposition of the individual to deal with the fungi in the gut," that affects the development of gut diseases, said study author David Underhill, an immunobiology professor at Cedar-Sinai Medical Center. "There may just be a group of people who are bad at handling fungi."
Inflammatory bowel diseases (IBDs) affect an estimated 1.4 million people in the U.S, with 30,000 new cases diagnosed each year. They are chronic conditions with no cure. With treatments, sometimes including surgery, doctors can manage patients’ symptoms, which include weight loss, bleeding, fatigue, diarrhea, loss of appetite and abdominal pain.
Based on their studies of fungal DNA in the intestines of mice and the feces of other mammals, including pigs, dogs and people, the researchers found that fungi make up a small but significant part of mammals' gut microbial communities.
In one experiment, the researchers removed the gene for a protein called Dectin-1 in mice. Mice that became deficient in Dectin-1 developed an overgrowth of fungi in their guts. Additionally, among the deficient mice, those that developed colitis had more-severe symptoms than control mice did, likely due to the additional fungi, the researchers said.
"Under certain conditions, the study has shown that fungi can make inflammatory intestinal disease even worse," Underhill said.
The researchers also found that mice with acute colitis experienced reduced symptoms when treated with anti-fungal drugs, suggesting a possible way to treat people with the condition.
"By adding an anti-fungal, it may be possible to bring that inflammation under control," said Dr. Michael Camilleri, a gastroenterologist at the Mayo Clinic who was not involved in the study. "The implication of that is that patients may avoid surgery."
IBDs can have severe consequences. Colitis can lead to intestinal ulcers and increases the risk of certain types of cancer. Crohn’s disease can cause malnutrition, and both diseases can create holes in the intestine wall.
While little is known about the cause of IBDs, many things — from eating certain foods to stress — may worsen them. The new research suggests certain types of fungi could be added to that list.
The results of the study are "very exciting," Camilleri said, because most evidence has suggested that gut fungi are "innocent bystanders." The new findings show how, under certain conditions, fungi "actually damage the intestine."
"The fascinating thing is it really opens the door to possibly treating this apparently innocuous fungus" with anti-fungal drugs, he said. Such drugs are accessible around the world, Camilleri noted.
Underhill said intestinal fungi are probably similar to intestinal bacteria, in that there are "good" bacteria that "occupy a niche that prevents bad bacteria from growing."
While the researchers found fungi in human fecal matter, their experiments primarily focused on mice, and they acknowledged their conclusions are limited. For example, there isn’t a model of Crohn’s disease in mice.
The authors said they hope next to study the role of fungi in the human gut.
The study was published on June 6 in the journal Science.
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