Fungi that live in the gut can be just as important for health and disease

The role of bacteria in gut health has received a lot of attention in recent years. But new research from scientists at the University of Utah Health shows that fungi, another microorganism that lives in us, can be just as important for health and disease.

The fungi thrive in the healthy gut, but they can also cause intestinal damage that can contribute to inflammatory bowel disease (IBD), according to the study published in Nature the 14th of July. Experiments with mice show that the immune system normally controls fungi, targeting the microbe when it goes into a state that can cause damage. When the system is out of balance, disease is more likely to occur.

“Fungi have been totally under-studied in part because they are vastly outnumbered by bacteria,” says June Round, Ph.D., professor of pathology at the U of U Health and senior author of the study. New tools and technologies are starting to make investigations like this possible, she adds. “This work adds an important element to the bigger picture.”

This knowledge opens up new avenues for the development of therapies aimed at improving intestinal health. The study shows proof of concept that one day vaccines could be used to fight gastrointestinal disease by enhancing natural immune responses that encourage a healthy balance of fungi and other gut microbiota.

A quest for balance

Round became interested in this line of research after noticing that a common medical test to diagnose Crohn’s disease, a type of IBD, works by detecting antibodies against fungi. And yet, how antibodies affect the influence of fungi on disease has yet to be explored.

To dig deeper, his team researched the trigger for the immune response. By working with patient samples and performing tests on mice, they determined that the yeast Candida albicans-; one of the main species of fungi that reside in the human intestine; elicited the strongest immune response. Further investigation showed that the antibodies focused on elongated types of fungal cells called hyphae, specifically binding to proteins called adhesins that help microbes stick to surfaces and become invasive.

With that target in hand, researchers could more definitively probe the role of fungi in gut health. They found that mice populated with yeast in its normal, rounded state remained healthy. In contrast, mice populated with Candidiasis in its invasive form caused intestinal damage that resembled IBD. The results show that normal antibody responses in the gut inhibit the disease by recognizing the harmful hyphae form of the fungi.

IBD is not the only health problem associated with fungi. Another is vaginal yeast infections. The researchers determined that a vaccine being studied as a remedy for yeast infection triggered an immune reaction against adhesin proteins that is similar to the reaction in Crohn’s patients. When inoculated with the vaccine, mice normally prone to IBD-type disease were less likely to develop the disease.

Researchers are now investigating whether vaccines could help alleviate IBD in humans and whether the same approach can be applied more broadly to shape other microbial communities in the gut. “We aim to harness interactions with commensal microbes and the host immune system to harness the microbial products for therapies,” Round said.

Healthy competition

In addition to the implications for the disease, the findings also suggest that fungi may be important in the healthy gut. Usually, the job of the immune system is to clear infections by getting rid of invading organisms. In this case, the fungi benefit from their interaction with the antibodies. The immune response pushes the fungi from their invasive state to their rounded and budding state, which improves their survival in the gut.

“The immune system is binding Candidiasis at its least pathogenic form, ”says Kyla Ost, Ph.D., a postdoctoral researcher in Round’s lab and lead author of the study. “This shows us that communication between host and microbe can be friendly, as opposed to antagonistic, in order to benefit both.