Study uncovers three-way relationships between gut fungi, genetics and disease risk

Some gut fungi have been implicated in intestinal diseases, however, human-fungi interactions are poorly understood, and scientists had previously thought gut fungi were determined by diet, according to the research team. To examine the relationship between human genetic variation and variation in gastrointestinal fungal communities, the researchers conducted a genome-wide association study (GWAS). They focused on the number and types of human genes influencing gut fungi abundance and the development of major chronic diseases.

"This research embarks on a first-in-kind journey to uncover the genetic underpinnings of the human gut mycobiome," said Emily Van Syoc, a postdoctoral researcher at Penn State at the time of the research and first author of the paper. "In a small discovery GWAS cohort that was validated in two larger datasets, we find that gut fungi, are associated with human genetic variants and, in turn, disease states. We are excited to continue pulling at this thread to unravel the forces that shape human gut fungi and contribute to health and disease."

"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 said. "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."

The researchers found a total of 148 fungi-associated genetic variants across seven chromosomes that statistically associate with nine fungal taxa, uncovering several genetic relationships with gut fungi and disease risk. The study was limited by a small cohort assessed for gut fungi in the Human Microbiome Project, but the connection with cardiovascular disease was validated in data from larger cohorts in the United Kingdom and a global consortium focused on coronary artery disease. Future studies may clarify if and how gut fungi mediate chronic disease risk, as well as reveal the mechanism by which genetic variation and gut fungi are connected, Bordenstein said.

"These results offer an exciting first glimpse into host genetic regulation of the mycobiome," Davenport said. "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."

The U.S. National Institutes of Health and Penn State funded the research.

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Penn State

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