Abstract
PURPOSE: The aim of this study is to explore the changes of gut microbiota, the metabolic characteristics and sex hormones in polycystic ovary syndrome with insulin resistance (PCOS-IR), and to clarify the role of gut microbiota in the occurrence of this condition. METHODS: We established a rat model of PCOS-IR using dehydroepiandrosterone (DHEA) combined with a high-fat diet, and recruited patients who met the clinical diagnostic criteria for PCOS-IR. We measured metabolic parameters and sex hormone profiles, and analyzed gut microbiota characteristics via high-throughput 16S rRNA sequencing. We also conducted microbial transplantation experiments to verify the causal relationship between gut microbiota and PCOS-IR. RESULTS: In PCOS-IR rats, we observed significant endocrine-metabolic disturbances and alterations in gut microbiota β-diversity, characterized by an enrichment of Fusobacterium. Transplantation of this dysbiotic microbiota to healthy rats reproduced key PCOS-IR features, confirming a causal role. In people with PCOS-IR, we found a distinct gut microbial profile compared to both healthy individuals and those with PCOS without IR, with Fusobacterium consistently identified as a key genus across species. CONCLUSION: Our findings show that gut microbiota disturbance leads to endocrine and metabolic features resembling PCOS-IR. The gut microbiota, particularly Fusobacterium, could serve as a clinical marker and potential therapeutic target for people with PCOS-IR. This study provides mechanistic insights into how gut microbiota contributes to PCOS-IR pathogenesis.