Gut fungi have been far less studied than other gut microbes such as bacteria and archaea said Emily Davenport assistant professor of biology at Penn State’s Eberly College of Science and co-author of the study. We know little about what shapes the gut mycobiome and its role in human health. Our findings show for the first time that host genetics can influence gut fungi and shed light on the physiological mechanisms governing their abundance. The study conducted by scientists at Penn State’s One Health Microbiome Center and published Sept. 2 in the open-access journal PLOS Biology addresses a key challenge in medicine. Clinicians’ ability to predict and manage chronic diseases is limited by uncertainties about disease-contributing factors said Seth Bordenstein, director of OHMC. Understanding how human genes interact with microorganisms could transform personalized diagnostics and biotherapeutics.

While some gut fungi have been linked to intestinal diseases human-fungi interactions remain poorly understood, and scientists previously believed diet was the primary determinant of gut fungi. To explore how human genetics influences gastrointestinal fungal communities the researchers conducted a genome-wide association study (GWAS), examining which genes affect gut fungi abundance and the risk of major chronic diseases. This research represents a first-of-its-kind effort to uncover the genetic basis of the human gut mycobiome said Emily Van Syoc a postdoctoral researcher at Penn State and first author of the study. In a small discovery cohort validated across two larger datasets we found that gut fungi are associated with human genetic variants and in turn with disease states. We look forward to further unraveling the factors that shape gut fungi and their impact on health and disease.

The researchers analyzed paired gut mycobiome and human genome data from 125 participants in the NIH’s Human Microbiome Project which investigates the microbial communities that inhabit the human body and their roles in health and disease. By identifying human genes linked to variations in specific gut fungi, they explored whether these gene-fungi relationships influence disease risk. We discovered numerous genetic connections to particular gut fungi and the link between the yeast Kazachstania and cardiovascular disease risk is especially intriguing for future studies said Seth Bordenstein. This work represents an important first step in understanding how human genetic variation shapes the largely understudied gut mycobiome.

The study identified 148 genetic variants across seven chromosomes linked to nine fungal taxa, revealing multiple connections between human genetics gut fungi and disease risk. Although the analysis was limited by the small cohort from the Human Microbiome Project, the association with cardiovascular disease was confirmed using larger datasets from the United Kingdom and an international coronary artery disease consortium. These findings provide an exciting first look at how host genetics regulate the mycobiome said Emily Davenport. Even more importantly, they raise new questions: Will associations differ across populations? Are there gene-mediated interactions between gut fungi and bacteria? We look forward to exploring the many avenues this research opens for understanding the role of gut fungi in health and disease.

Source: https://www.psu.edu/news/eberly-college-science/story/connection-among-gut-fungi-genetics-and-disease-risk-humans-identified