A newly identified fungus found in the stomachs of mice may provide insights into the evolution of fungi in the gastrointestinal system, according to recent research from Weill Cornell Medicine. This discovery indicates that previous preclinical research may have missed an important factor influencing mouse biology.
A newly identified fungus found in the stomachs of mice may provide insights into the evolution of fungi in the gastrointestinal system, according to recent research from Weill Cornell Medicine. This discovery indicates that previous preclinical research may have missed an important factor influencing mouse biology.
Researchers have increasingly recognized the crucial role that gut-dwelling microbes, often referred to as “commensals,” play in human health and illness. These bacteria, for instance, significantly influence human immunity, and changes in their populations have been linked to various health issues, including cancers, inflammatory conditions, and even depression. However, the effects of fungal commensals on immunity are less understood, largely due to the absence of a solid mouse model for studying fungal commensalism.
The study, published on November 27 in Nature, highlights that a yeast named Kazachstania pintolopesii, which is plentiful in the stomachs of wild mice, is highly adapted to these animals. This fungus enhances their immune defense against parasites but also makes them more susceptible to certain allergies.
“For many years, we have been searching for a genuine fungal commensal in mice. However, the fungal populations in laboratory mice, as revealed by DNA analysis, tend to be inconsistent and greatly differ from one colony to another,” explained Dr. Iliyan Iliev, a senior author of the study and an associate professor of immunology.
In a 2019 study led by Dr. Barbara Rehermann from the National Institutes of Health, it was discovered that lab mice raised with gut microbes resembling those of wild mice respond more effectively to human immune responses compared to conventional lab mice. Dr. Iliev’s lab found these “wildling” mice had significantly higher levels of fungal DNA in their guts than what was previously noted in standard lab mice.
“This initiated a kind of investigative journey as we searched for the main fungus, expanding our research into various mouse populations,” Dr. Iliev remarked. “And where better to find wild mice than in New York City?”
The researchers sought signs of the fungus in fecal samples and other materials collected from pest control companies in New York City and Los Angeles, as well as samples from various research institutions that utilize or sell lab mice. Ultimately, they confirmed that K. pintolopesii is very common in wild mice and frequently present in lab mouse colonies, often without researchers being aware of it.
“The presence or absence of this fungus should be considered in various types of mouse studies,” remarked Dr. Yun Liao, a co-first author and postdoctoral researcher in the Iliev laboratory.
“K. pintolopesii can significantly alter the outcomes of experiments,” stated Dr. Iris Gao, another co-first author who was a graduate student in Iliev’s lab during the investigation.
The study revealed that K. pintolopesii can quickly colonize the guts of lab mice, is reliably passed on to newborn mice, and manages to evade the antifungal defenses of its host while partially inhibiting the growth of other fungal species. This indicates that this fungus has adapted over time to thrive in mice, functioning as a genuine commensal organism.
However, changes in gastrointestinal mucus due to dietary shifts or the use of antibiotics can make the fungus noticeable to the immune system by triggering the production of a cytokine called IL-33. This cytokine activates what is known as a “type 2” immune response. The fungus benefits its hosts by suppressing other fungal species and aiding in defense against worms through this enhanced immune response, but it also worsens food allergies, the research team found.
If your research involves allergies, parasitic infections, cancer progression, or any area related to type 2 or type 17 immune responses, this fungus might be a crucial factor that should not be ignored, Dr. Iliev advised.
While this study indicates that K. pintolopesii is a promising model for studying fungal commensalism, it also raises pertinent questions: Is this fungus a routine part of the mouse microbiota that should always be present in lab mice, especially in immunological studies? Is there a similar fungal commensal in humans that promotes type 2 immunity?
Dr. Iliev and his team are currently investigating these questions by analyzing samples collected from various locations across the continent in collaboration with multiple institutions, including the Broad Institute, the National Institutes of Health, and Penn State.
