Ulcerative colitis linked to intestinal fungi
Bacteria in the gut play a crucial role in human health, and imbalances in bacterial populations can contribute to many disorders. New research suggests that fungi, though not as common in the intestines as bacteria, may also play a role in causing and modulating disease.
The results could lead to new treatments for conditions such as inflammatory bowel disease, ulcerative colitis and Crohn's disease. An estimated 1.4 million Americans have some form of inflammatory bowel disease, which can cause inflammation, ulcers in the bowel, abdominal pain, diarrhea, bleeding, fatigue, weight loss and loss of appetite. An additional 30,000 cases are diagnosed annually.
An estimated 100 trillion individual bacteria reside in the intestines -- more than the number of cells in the human body. They play crucial roles, such as aiding digestion of food, producing necessary vitamins and suppressing the growth of harmful microbes.
But according to Dr. David M. Underhill of the Inflammatory Bowel and Immunobiology Research Institute at Cedars-Sinai Medical Center, there has been little corresponding study of fungi in the intestine.
Working with mice, Underhill and his colleagues looked for fungal DNA in the animals' bowels. The team reported in the journal Science that they identified more than 100 species. "We were truly stunned to see just how common fungi are," he said.
The body's immune response to fungi is mediated by a protein called Dectin-1, which is produced by white blood cells and kills fungi. The team found that mice with a defective form of Dectin-1 were far more susceptible to developing ulcerative colitis than those with the normal form. When the mice with defective Dectin-1 and ulcerative colitis were given fluconazole, a drug commonly used to kill fungus, their symptoms moderated.
Underhill's team then looked at the Dectin-1 gene in humans. They found that the mutated form of the gene for Dectin-1 was much more common in patients with what is known as medically refractory ulcerative colitis -- that is, ulcerative colitis that does not respond to medical therapy, such as systemic corticosteroids, cyclosporine and biological therapies.
Intriguingly, the defective form of the gene, known as CLEC7A, has not been linked to ulcerative colitis in any genome-wide association studies.
The researchers' conclusion is not that the defective gene allows fungi to produce inflammatory bowel disease such as ulcerative colitis. Rather, they suggest that the presence of the defective gene makes the disease much more severe when it is caused by other things, but that treating the fungi might be of some help in treating the disease.
"Overall, the idea that fungi are present in the gut and that they interact strongly with the immune system will fundamentally alter how we think about the gut microflora and inflammatory bowel diseases," they concluded.