The role of bacteria in intestinal health has received a lot of attention in recent years. But new research led by scientists at the University of Utah Health shows that fungal; another microorganism that lives in us-; can be just as important in health and illness.
Fungi bloom 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 on July 14th. Experiments with mice show that the immune system normally keeps fungi under control, targeting the microbe when it enters a state that can cause damage. When the system is out of balance, illness occurs more often.
“Fungi have been fully investigated in part because they are much smaller than bacteria,” says June Round, Ph.D., professor of pathology at U or U Health and senior author of the study. New tools and technologies are beginning to enable research like this, she adds. “This work adds an important piece to the bigger picture.”
These insights open up new avenues for developing therapies to improve gut health. The study shows evidence of concept that vaccines can one day be used to control gastrointestinal disease by enhancing natural immune responses that stimulate a healthy balance of fungi and other intestinal microbiota.
A quest for balance
Round became interested in this line of research after noting that a common medical test for diagnosing Crohn’s disease, a type of IBD, works by detecting antibodies against fungi. And yet, how antibodies affect fungal disease has yet to be investigated.
To dig deeper, her team looked for the trigger of the immune response. Working with patient samples and performing tests with mice, they determine that the yeast Candida albicans-; one of the most important types of fungi living in the human gut; elicits the strongest immune response. Further research showed that antibodies zeroed in on elongated fungal types called hyphae, specifically bound to egg proteins called adhesins that help microbes maintain surfaces and become invasive.
With this goal in hand, the researchers were able to more definitively investigate the role of fungi in intestinal health. They found that mice populated with the yeast in its normal, depleted state remained healthy. In contrast, mice populated with Candida in its invasive form causes intestinal damage similar to IBD. The results show that normal anti-inflammatory responses in the gut inhibit disease by recognizing the harmful, hyphal form of fungi.
IBD is not the only health care associated with fungi. Another is vaginal yeast infections. The researchers concluded that a vaccine being studied as a remedy for yeast infection elicited an immune response against adhesin proteins that is similar to the reaction in Crohn’s patients. When vaccinated with the vaccine, mice were normally susceptible to an IBD-like condition less likely to develop the disease.
Researchers are now investigating whether vaccines can help IBD reduce people; and whether the same approach can be applied more broadly to form other microbial communities in the gut. “We aim to use interactions with commensal microbes and the host’s immune system to use microbial products for therapies,” says Round.
In addition to consequences for disease, the findings also suggest that fungi may be important in the healthy gut. Typically, the task of the immune system is to eradicate infections by getting rid of invasive organisms. In this case, fungi benefit from their interaction with antibodies. The immune response produces fungi from their invasive state in their round, emerging state, which improves their survival in the gut.
“The immune system is limited Candida to its least pathogenic form, “says Kyla Ost, Ph.D., a postdoctoral researcher in the lab of Round and the lead author of the study.” This shows us that the communication between host and microbe can be friendly, as opposed to antagonistic, in order to benefit both. “
University of Utah Health
Ost, KS, and others. (2021) Adaptive immunity causes mutualism between commensal eukaryotes. Nature. doi.org/10.1038/s41586-021-03722-w.