Fungal jungle: Scientists discover first genetic, mycobiome & chronic disease risk links

New research finds evidence of a previously unknown three-way relationship between human genetics, the gut mycobiome, and the risks of developing chronic diseases. Nutrition Insight speaks to a study author to learn how the finding opens the door to exploring the fungal biosphere, as the mycobiota is an often-overlooked part of the gut microbiome.

The Pennsylvania State University, US, researchers note that physicians’ lack of knowledge about what contributes to disease risks limits their ability to treat chronic diseases. They point to the gut fungi as drivers of intestinal diseases. Previously, scientists thought gut fungi were determined by diet.

To determine which fungi are linked to genetic variation, researchers carried out a genome-wide association study. They found 148 fungi-associated variants across seven chromosomes that statistically associate with nine fungal taxa. This reveals a link between gut fungi and human genes.

“Fungi can be diet-derived and diet-influenced. That means the foods you eat may carry fungal cells that end up inside your gut, or the foods provide the nutrients for resident gut fungi to survive,” co-corresponding author Seth Bordenstein, Ph.D., tells us. He is the director of the One Health Microbiome Center and professor of Biology and Entomology.

“Since diet plays a crucial role in the development of inflammation and disease, as well as the structure of the gut fungi, it will be important to study if and how genetic variants in the human genome hinder or accelerate the response of the gut fungi to dietary influences.”

No longer blind to fungi

First author Emily van Syoc notes that commensal Kazachstania were discovered to be linked with human genetic variants and, in turn, disease states. 

It is important to study how human genetic variants affect gut fungi’s response to diet influences.“This research is our first major step toward understanding the impacts of human genetic variation on a very understudied group of gut microorganisms — the mycobiome — or community of fungal species that occur in our intestinal tracts,” says Bordenstein.

“We’ve uncovered a surprising number of genetic links to specific gut fungi, and our discovery of a connection between a particular yeast, Kazachstania, and cardiovascular disease risk is particularly interesting for future studies and validation.”

Bordenstein adds that academia and industry have overlooked the possibility that gut fungi play a role in human health, which has not been tested extensively nor largely. 

“But part of the motivation of our work is to ensure that we no longer have a blind eye for these microorganisms in scientific studies and applications.” 

Cohort and future studies

The publication in PLOS Biology examined the data from 125 individuals from the Human Microbiome Project, launched by the US National Institutes of Health to identify microorganisms in humans and their role in health and disease.

Although the cohort was small, the researchers say the results were supported by an independent larger cohort. They suggest that future studies could provide deeper insights into how gut fungi might influence chronic disease risk. This could also help clarify the mechanisms connecting gut fungi and genetic variation.

“Determining whether human genetics simultaneously associates with differential microbial abundance and disease risk is a central challenge to resolve with substantive potential for personalized diagnostics and/or biotherapeutics,” suggest the study authors.

The researchers found a link between human genetics, Kazachstania, and cardiovascular disease risk.“The findings establish previously unrecognized connections between human genetics, gut fungi, and chronic disease, broadening the paradigm of human-microbe interactions in the gut to the mycobiome. Taken together, this work advances the canonical, two-dimensional focus on human genetics and gut bacteria to the gut fungal biosphere.”

World of wonder

Study co-author Emily Davenport notes that gut fungi are understudied compared to the gut bacteria and archaea. “We know much less about what determines the fungi that reside in the gut and whether they are important for human health.” 

“These results demonstrate for the first time that host genetics can influence the fungi that live in the gut and provide clues about the physiological mechanisms that determine their abundances.”

“Even more exciting, they open up many more questions about how that occurs. Will we see different associations in different populations? Are there interactions between gut fungi and gut bacteria that are modulated by genetics? We are excited to see the new avenues this research opens up.”

An intricate and dynamic ecosystem is created by the complex interactions between gut bacteria and fungi, details Bordenstein. However, he warns of risks of treatments that do not consider the role of gut fungi. “Antibacterial treatments such as antibiotics will not only eliminate or reduce bacterial pathogens and their signaling molecules, but they can indirectly alter the abundance of fungi that co-occur with and depend on these bacteria and molecules.”  

“Fungal pathogens may bloom when certain bacteria are antibiotically eliminated. As a consequence, scientific investigations may need to stay more vigilant of key fungal determinants of health when antibacterial treatments are used.” 

Nutrition Insight recently spoke to researchers who warned that antibiotic treatment unintentionally makes the gut a more hospitable environment for drug-resistant enterococci. Probiotics are being explored as a new approach in microbiome-based therapies against these antibiotic-resistant superbugs that cause hospital-acquired infections. 

We also spoke to a researcher about a review of the mycobiota, which opens an underexplored challenge for developing new nutrition solutions. It revealed probiotics and diets influencing this environment.