Fungi that live in the gut can be equally important to health and disease

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The role of bacteria in gut health has received a lot of attention in recent years. But new research, led by scientists from the University of Utah Health, shows that fungi – another microorganism that lives inside us – can be important to health and disease alike.

Fungi thrive in healthy intestines, but can also cause intestinal damage, which 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 usually keeps fungi in check and attacks the microbe when it enters a state that can cause harm. When the system is out of whack, illness is more likely to occur.

“Fungi have been completely under-researched in part because they are far inferior to bacteria,” says June Round, Ph.D., professor of pathology at the University of U Health and lead author of the study. New tools and technology are making research like this possible, she adds. “This work adds an important piece to the overall picture.”

These findings open new avenues for the development of therapeutics to improve gut health. The study shows that vaccines could one day be used to curb gastrointestinal disease by boosting the natural immune responses that promote a healthy balance of fungi and other gut microbiota.

A search for balance

Round became interested in this line of research after discovering that a common medical test used to diagnose Crohn’s disease, a type of IBD, works by detecting antibodies to fungus. How antibodies influence the influence of fungi on diseases, however, still had to be researched.

To dig deeper, her team looked for what triggered the immune response. Using patient samples and tests with mice, they found that the yeast Candida albicans-; one of the most important types of fungus that live in the human intestine; triggered the strongest immune response. Further research showed that antibodies were directed to elongated types of fungal cells called hyphae, which specifically bind to proteins called adhesins, which help microbes adhere to surfaces and become invasive.

With that goal in hand, the researchers were able to take a closer look at the role mushrooms played in intestinal health. They found that mice colonized with the yeast in its normal, rounded state stayed healthy. In contrast, mice populated with candidate 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 fungi.

IBD isn’t the only health condition associated with fungus. Another is vaginal yeast infections. The researchers found that a vaccine studied as a yeast cure elicited an immune response against adhesin proteins similar to the response seen in Crohn’s disease. When vaccinated with the vaccine, mice, which were usually prone to an IBD-like condition, were less likely to develop disease.

Researchers are now investigating whether vaccines could help alleviate IBD in humans and whether the same approach can be more broadly applied to shape other microbial communities in the gut.

Our goal is to use interactions with commensal microbes and the host’s immune system to make microbial products useful for therapies. “

June Round, Ph.D., Professor of Pathology, U of U Health

Healthy competition

In addition to the effects on disease, the results also suggest that mushrooms may be important for a healthy gut. Typically, the immune system’s job is to clear infections by getting rid of invasive organisms. In this case, fungi benefit from their interaction with antibodies. The immune response brings fungi from their invasive state to their round, budding state, which improves their survival in the gut.

“The immune system is limiting candidate to their least pathogenic form, “says Kyla Ost, Ph.D., postdoctoral fellow in Round’s lab and lead author of the study.” This shows us that communication between host and microbe can be friendly rather than antagonistic in order to benefit both. “

Source:

University of Utah Health

Journal reference:

East, KS, et al. (2021) Adaptive Immunity Induces Mutualism Between Commensal Eukaryotes. Nature. doi.org/10.1038/s41586-021-03722-w.



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