2. Academic Validation
  3. The intestinal fungus Aspergillus tubingensis promotes polycystic ovary syndrome through a secondary metabolite

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

  • Cell Host Microbe. 2025 Jan 8;33(1):119-136.e11. doi: 10.1016/j.chom.2024.12.006.
Jiayu Wu 1,  Kai Wang 1,  Xinyu Qi 2,  Shuang Zhou 1,  Shuyun Zhao 3,  Meisong Lu 4,  Qixing Nie 5,  Meng Li 6,  Mengwei Han 7,  Xi Luo 6,  Chuyu Yun 2,  Pengcheng Wang 8,  Rong Li 2,  Chao Zhong 9,  Xiaofei Yu 10,  Wen-Bing Yin 11,  Changtao Jiang 12,  Jie Qiao 13,  Yanli Pang 14
Affiliations

Affiliations

  • 1 State Key Laboratory of Female Fertility Promotion, Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China; Department of Immunology, School of Basic Medical Sciences, State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing 100191, China; NHC Key Laboratory of Medical Immunology, Peking University, Beijing, China.
  • 2 State Key Laboratory of Female Fertility Promotion, Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China; Institute of Advanced Clinical Medicine, Peking University, National Clinical Research Center for Obstetrics and Gynecology (Peking University Third Hospital), Beijing, China; Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing, China.
  • 3 Reproductive Medicine Center, Department of Obstetrics and Gynecology, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China.
  • 4 The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
  • 5 State Key Laboratory of Female Fertility Promotion, Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China.
  • 6 Department of Physiology and Pathophysiology, Center for Obesity and Metabolic Disease Research, School of Basic Medical Sciences, State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing 100191, China.
  • 7 Institute of Systems Biomedicine, School of Basic Medical Sciences, Peking University Health Science Center, Beijing Key Laboratory of Tumor Systems Biology, Beijing, China.
  • 8 Center of Basic Medical Research, Institute of Medical Innovation and Research, Peking University Third Hospital, Beijing, China.
  • 9 Department of Immunology, School of Basic Medical Sciences, State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing 100191, China.
  • 10 State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai 200438, China.
  • 11 State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
  • 12 State Key Laboratory of Female Fertility Promotion, Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China; Department of Immunology, School of Basic Medical Sciences, State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing 100191, China.
  • 13 State Key Laboratory of Female Fertility Promotion, Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China; Institute of Advanced Clinical Medicine, Peking University, National Clinical Research Center for Obstetrics and Gynecology (Peking University Third Hospital), Beijing, China; Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing, China. Electronic address: jie.qiao@263.net.
  • 14 State Key Laboratory of Female Fertility Promotion, Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China; Institute of Advanced Clinical Medicine, Peking University, National Clinical Research Center for Obstetrics and Gynecology (Peking University Third Hospital), Beijing, China; Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing, China. Electronic address: yanlipang@bjmu.edu.cn.
PMID: 39788092 DOI: 10.1016/j.chom.2024.12.006
Abstract

Polycystic ovary syndrome (PCOS) affects 6%-10% of women of reproductive age and is known to be associated with disruptions in the gut bacteria. However, the role of the gut mycobiota in PCOS pathology remains unclear. Using culture-dependent and internal transcribed spacer 2 (ITS2)-sequencing methods, we discovered an enrichment of the gut-colonizable fungus Aspergillus tubingensis in 226 individuals, with or without PCOS, from 3 different geographical areas within China. Colonization of mice with A. tubingensis led to a PCOS-like phenotype due to inhibition of Aryl Hydrocarbon Receptor (AhR) signaling and reduced interleukin (IL)-22 secretion in intestinal group 3 innate lymphoid cells (ILC3s). By developing a strain-diversity-based-activity metabolite screening workflow, we identified secondary metabolite AT-C1 as an endogenous AhR antagonist and a key mediator of PCOS. Our findings demonstrate that an intestinal fungus and its secondary metabolite play a critical role in PCOS pathogenesis, offering a therapeutic strategy for improving the management of the disease.

Keywords

PCOS; gut microbiota; gut mycobiota; secondary metabolite.

Figures
Products