The gut microbiome has received a lot of attention, but new research shows that fungi in the gut are also an important microorganism in gut functioning and health, which then affects human health.
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Contrasting effects of fungal communities in the gut
In recent years, the role of microbial diversity and richness in the gut has prompted extensive research into the benefits of maintaining a healthy gut microbiome. This has led to the rise of probiotic supplements, microbial treatments, but research now shows that bacterial communities are not the only actors in the gut generating such benefits.
In a new study from scientists at the University of Utah Health, fungi have been shown to also be key players in the balance of healthy gut functioning. The study, published in the journal Nature, describes how fungi thrive in a healthy gut, but they can also cause intestinal damage that may contribute to inflammatory bowel disease (IBD).
Fungi have been wholly understudied in part because they are vastly outnumbered by bacteria. This work adds an important piece to the bigger picture."
June Round, Ph.D., Professor of Pathology at U of U Health
To explore the role of fungi in the gut, researchers conducted experiments with mice to demonstrate how a healthy immune system maintains a healthy diversity and abundance of fungi, but when the system is unbalanced, IBD is more likely to occur. Initial hypotheses were made after Round noted that a common medical test for diagnosing Crohn's disease, a type of IBD, relies on detecting antibodies against fungi, but the role of fungi itself on the antibodies is unknown.
To address this knowledge gap, researchers searched for the trigger of the immune response to IBD. Data from patient samples affected by the disease were used to design experiments on mice, from which the researchers found that the yeast Candida albicans elicited the strongest immune response. This species is one of the main species of fungi that reside in the human gut, providing key insights for the team to explore the role of gut fungi further.
Following detection, the scientists found the antibodies produced by the immune response targeted hyphae, which are fungal cell types, that bind to proteins helping microbes adhere to surfaces and become invasive. This mechanism was key proof for researchers to demonstrate fungi’s role in balancing gut health.
A fragile balancing act in the gut but with potential supporting treatments
Using a series of experiments on mice, researchers found that mice inoculated with Candida in its normal state remained healthy, but when administered with Candida in its invasive form, it caused intestinal damage that resembled IBD. The results demonstrated how a healthy antibody response in the gut inhibits disease by recognizing the harmful, hyphal form of fungi.
However, IBD is just one of many health conditions associated with fungi, which also include conditions such as vaginal yeast infections. The researchers, therefore, used existing vaccinations tested for yeast infections and found that the vaccine triggered an immune reaction against adhesin proteins that is similar to the reaction in Crohn's patients.
The vaccine was effective in the mouse population prone to an IBD-like condition, and researchers are now confident that similar vaccines could help mitigate IBD and related conditions in people.
Kyla Ost, Ph.D., a postdoctoral researcher in Round's lab and the study's lead author describes; "The immune system is constraining Candida to its least pathogenic form," adding, "This is showing us that the communication between host and microbe can be friendly, as opposed to antagonistic, to benefit both."
Usually, a typical immune response is to clear infections by eliminating invasive organisms. However, fungi benefit from their interaction with antibodies, as they prod fungi from their invasive state into their rounded, budding state, which improves fungal survival in the gut.
These findings provide important insights into gut functioning as it is the first study showing that fungi benefit from antibody production, which could offer potential treatments to curb gastrointestinal diseases, but also that fungi are key to maintaining a healthy gut.