Clinicians’ ability to diagnose and treat chronic diseases has long been hindered by uncertainties surrounding the factors contributing to disease risk. A groundbreaking study published on September 2nd in the open-access journal PLOS Biology by researchers at The Pennsylvania State University unveils the first known connections between human genetic variation, gut mycobiome diversity, and the risk of developing chronic diseases.
Drs. Emily Van Syoc, Emily Davenport, and Seth Bordenstein spearheaded this research, which challenges the previous assumption that gut fungi are primarily determined by diet. Instead, their findings suggest a more complex interaction involving human genetics. Through a genome-wide association study (GWAS) involving data from 125 individuals provided by the Human Microbiome Project, the researchers identified 148 fungi-associated variants (FAVs) across seven chromosomes. These variants are linked to nine different fungal taxa, establishing a significant connection between genetic loci, gut fungi, and disease risk.
Unveiling the Gut Fungi-Genetics Connection
The study highlights the role of gut fungi in intestinal diseases, an area that has been largely overlooked compared to bacterial studies. The researchers’ findings indicate that human genetic variation influences the abundance and types of gut fungi, which in turn may affect disease risk. This discovery opens new avenues for understanding the complex interplay between genetics and the gut microbiome.
According to the authors, “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.” The findings broaden the paradigm of human-microbe interactions in the gut to include the mycobiome, advancing the traditional focus on human genetics and gut bacteria to the fungal biosphere.
Expert Insights and Implications
Co-corresponding author Seth Bordenstein emphasized the significance of this research as a first step toward understanding the impacts of human genetic variation on the mycobiome. “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 noted.
Coauthor Emily Davenport highlighted the under-researched nature of gut fungi compared to other gut microbes. “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,” she said. Davenport also pointed out the potential for this research to lead to new questions about genetic regulation of the mycobiome and its interactions with other gut microbes.
Challenges and Future Directions
While the study’s small cohort size presents limitations, a key result was validated in an independent, larger cohort, underscoring the robustness of the findings. The researchers are optimistic that future studies will further elucidate how gut fungi mediate chronic disease risk and the mechanisms by which genetic variation influences fungal communities.
First author Emily Van Syoc expressed excitement about the potential of this research to unravel the genetic underpinnings of the human gut mycobiome. “In a small discovery GWAS cohort, we find that gut fungi, in particular the commensal Kazachstania, are associated with human genetic variants, and in turn, disease states,” she remarked. “We are excited to continue pulling at this thread to unravel the forces that shape human gut fungi and contribute to health and disease.”
Broader Implications for Personalized Medicine
The implications of these findings are profound, suggesting a future where personalized medicine could be informed by an individual’s genetic predisposition to certain gut fungi. This could lead to more targeted therapies and diagnostics, particularly for chronic diseases where the gut microbiome plays a critical role.
As the researchers continue to explore the genetic links to gut fungi, their work promises to deepen our understanding of the gut microbiome’s role in health and disease. This research not only challenges existing paradigms but also sets the stage for a new era of microbiome research that includes the often-overlooked fungal component.
For more detailed insights, the full study is available in PLOS Biology and can be accessed here.
Citation: Van Syoc EP, Davenport ER, Bordenstein SR (2025) Gut fungi are associated with human genetic variation and disease risk. PLoS Biol 23(9): e3003339. https://doi.org/10.1371/journal.pbio.3003339
This research was supported by funding from Pennsylvania State University and various grants, with no influence from the funders on the study’s design or outcomes.
