The intestinal fungus Aspergillus tubingensis promotes polycystic ovary syndrome through a secondary metabolite.

Summary

Across three Chinese cohorts (n=226), the gut fungus Aspergillus tubingensis was enriched in PCOS and induced a PCOS-like phenotype upon colonization in mice by inhibiting AhR signaling and decreasing IL-22 in ILC3s. A strain-diversity metabolite screen identified AT-C1 as an endogenous AhR antagonist mediating the phenotype. This establishes a mycobiome-derived mechanism for PCOS and nominates AhR signaling restoration as a therapeutic strategy.

Key Findings

• Aspergillus tubingensis was enriched in the gut of PCOS cohorts across three regions (total n=226).
• Colonization with A. tubingensis induced PCOS-like phenotypes in mice via inhibition of AhR signaling and reduced IL-22 from ILC3s.
• A strain-diversity-based metabolite screen identified AT-C1 as an endogenous AhR antagonist that mediated PCOS features.

Clinical Implications

Suggests screening the gut mycobiome in PCOS and exploring AhR pathway–modulating interventions (e.g., AhR agonists, microbiome/mycobiome modulation) as adjunctive therapies alongside lifestyle and ovulatory treatments.

Limitations

• Human cohorts were restricted to three regions in China, potentially limiting generalizability.
• Causality in humans remains to be proven and metabolite exposure levels in human gut remain to be quantified.

Future Directions

Validate fungal prevalence and AT-C1 levels in diverse populations; test AhR-targeted or mycobiome-modulating therapies in PCOS; delineate dietary and environmental modifiers of the mycobiome–endocrine axis.