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Gut fungi are associated with human genetic variation and disease risk

Summary

Researchers discovered for the first time how human genes influence the fungi living in our gut and how this connection affects heart disease risk. They found that a yeast called Kazachstania is regulated by a gene called CDH13, and people with certain genetic variants have less of this beneficial yeast and higher risk of heart disease. This groundbreaking study shows that our genetics don’t just affect bacteria in our gut—they also shape our fungal community, which has real implications for heart health.

Background

While human genetic influences on gut bacteria have been extensively studied, the genetic determinants of the gut mycobiome (fungal community) remain largely unexplored. Gut fungi may play important roles in human health and disease, yet have been understudied compared to bacterial components of the microbiome.

Objective

To conduct the first genome-wide association study (GWAS) on human genetic variants influencing gut fungal abundance and to determine whether these genetic-fungal associations link to chronic disease risk, particularly focusing on cardiovascular disease.

Results

The researchers identified 148 fungi-associated variants (FAVs) across 7 chromosomes associated with 9 fungal taxa, with several variants located in protein-coding genes (PTPRC, ANAPC10, NAV2, CDH13). Notably, the yeast Kazachstania associated with genetic variation in CDH13 and showed a causal relationship with cardiovascular disease risk in Mendelian randomization analysis.

Conclusion

This study establishes previously unrecognized connections between human genetics, gut fungi, and chronic disease, expanding the understanding of human-microbe interactions beyond bacteria to include the mycobiome. The findings suggest potential applications for precision diagnostics and personalized medicine approaches to cardiovascular disease and other conditions.
  • Published in:PLoS Biology,
  • Study Type:Genome-wide Association Study,
  • Source: 10.1371/journal.pbio.3003339; PMID: 40892706
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