Fungi that live in the gut influence health and disease
Vaccines that balance gut microbial communities may one day be used to
improve gastrointestinal health

Date:
July 14, 2021
Source:
University of Utah Health
Summary:
Bacteria's role in gut health has received attention in recent
years. But new research shows that fungi -- another microorganism
that lives within us -- may be equally important in health and
disease. Fungi thrive in the healthy gut, but when interactions
with the immune system are off- balance, they cause intestinal
damage that may contribute to gastrointestinal disease. Additional
investigation demonstrate that vaccines could be developed as
therapeutics to improve gut health.



FULL STORY ========================================================================== Bacteria's role in gut health has received a lot of attention in recent
years.

But new research led by scientists at University of Utah Health shows
that fungi -- another microorganism that lives within us -- may be
equally important in health and disease.


========================================================================== Fungi thrive in the healthy gut, but they can also cause intestinal damage
that may contribute to inflammatory bowel disease (IBD), according to
the study published in Nature on July 14. Experiments with mice show that normally, the immune system keeps fungi in check, targeting the microbe
when it switches into a state that can cause harm. When the system is off-balance, disease is more likely to occur.

"Fungi have been wholly understudied in part because they are
vastly outnumbered by bacteria," says June Round, Ph.D., professor of
pathology at U of U Health and the study's senior author. New tools and technologies are starting to make investigations like this one possible,
she adds. "This work adds an important piece to the bigger picture."
These insights open new avenues for developing therapeutics to improve
gut health. The study shows proof of concept that, one day, vaccines
could be used to curb 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 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 fungi's influence on disease had yet to be explored.



==========================================================================
To dig deeper, her team searched for the trigger of the immune response.

Working with patient samples and carrying out tests with mice,
they determined that the yeast Candida albicans -- one of the main
species of fungi that reside in the human gut -- elicited the strongest
immune response. Further investigation showed that antibodies zeroed
in on elongated fungal cell types called hyphae, specifically binding
to proteins called adhesins that help microbes stick to surfaces and
become invasive.

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

IBD isn't the only health condition associated with fungi. Another is
vaginal yeast infections. The researchers determined that a vaccine
being investigated 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 an IBD-like condition were less likely to develop disease.

The researchers are now investigating whether vaccines could help
mitigate IBD in people -- and whether the same approach can be applied
more broadly to shape other microbial communities in the gut. "We aim to exploit interactions with commensal microbes and the host immune system
to harness microbial products for therapies," Round says.

Healthy competition In addition to implications for disease, the findings
also suggest fungi may be important in the 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 reaction prods fungi from their invasive state into their rounded, budding state, which improves their survival in the gut.

"The immune system is constraining Candida to its least pathogenic
form," says Kyla Ost, Ph.D., a postdoctoral researcher in
Round's lab and the study's lead author. "This is showing
us that the communication between host and microbe can be
friendly, as opposed to antagonistic, in order to benefit both." ========================================================================== Story Source: Materials provided by University_of_Utah_Health. Note:
Content may be edited for style and length.


========================================================================== Journal Reference:
1. Kyla S. Ost, Teresa R. O'Meara, W. Zac Stephens, Tyson Chiaro,
Haoyang
Zhou, Jourdan Penman, Rickesha Bell, Jason R. Catanzaro, Deguang
Song, Shakti Singh, Daniel H. Call, Elizabeth Hwang-Wong, Kimberly
E. Hanson, John F. Valentine, Kenneth A. Christensen, Ryan
M. O'Connell, Brendan Cormack, Ashraf S. Ibrahim, Noah W. Palm,
Suzanne M. Noble, June L.

Round. Adaptive immunity induces mutualism between commensal
eukaryotes.

Nature, 2021; DOI: 10.1038/s41586-021-03722-w ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/07/210714110525.htm

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