Groundbreaking Study Reveals Genetic Connections Between Gut Fungi, Human Genes, and Disease Risk

Recent research has uncovered the first evidence linking human genetic variation to gut fungal communities, shedding light on how these interactions may influence health and disease. Published on September 2, 2025, in PLOS Biology, the study led by scientists from Pennsylvania State University examined the complex relationships between human genes, gut fungi (mycobiome), and chronic disease risk.

Gut fungi are known to be involved in various intestinal conditions, yet their role and determinants remain poorly understood. Traditionally, diet was thought to be the primary factor influencing fungal communities in the gut. However, this new study challenges that view by demonstrating a genetic basis for the composition of the gut mycobiome.

Researchers conducted a genome-wide association study (GWAS) utilizing paired gut mycobiome and human genome data from 125 individuals obtained via the Human Microbiome Project. They identified 148 genetic variants (Fungi-Associated Variants, FAVs) spread across seven chromosomes, which are statistically linked to nine different fungal taxa. These findings suggest that certain human genetic factors influence the prevalence of specific fungi in the gut.

Further analysis indicated that some of these genetic variants are also associated with disease risk, although the cohort size was limited. Notably, a key validation was achieved in an independent, larger cohort, confirming the reproducibility of the findings. The study paves the way for future research into how gut fungi may mediate chronic disease development and how genetic variation modulates this relationship.

Scientists emphasize the significance of these results in expanding our understanding of host-microbe interactions, particularly highlighting the dynamic role of the gut mycobiome. The discovery of genetic links to specific fungi, including the yeast Kazachstania—which they found to be connected to cardiovascular disease risk—is of particular interest.

Authors such as Seth Bordenstein and Emily Davenport highlight that this research broadens the traditional focus from gut bacteria to include fungi, revealing new avenues for personalized diagnostics and therapeutics. The findings suggest that host genetics not only influence bacterial populations but also play a crucial role in shaping the gut fungal landscape.

Lead researcher Emily Van Syoc notes that this pioneering work aims to understand the genetic factors controlling the mycobiome and their contribution to health and disease. The research opens numerous questions about the variability of these associations across different populations and potential interactions between fungi and bacteria, ultimately advancing our knowledge of microbial involvement in human health.