Characteristic Gut Microbiota in PCOS-IR Patients and Its Association with Endocrine Features

Wenyi Liang,1,* Yanning Yao,2,* Xinyang Ren,3 Anran Xue,4 Mengcheng Cai,2 Jin Yu,2 Chaoqin Yu,2 Ling Zhou,2 DongXia Zhai2 1School of Pharmacy, Naval Medical University, Shanghai, People’s Republic of China; 2Department of Gynecology of Traditional Chinese Medicine, Changhai Hospital, Naval Medical University, Shanghai, People’s Republic of China; 3Shanghai Pinghe School, Shanghai, People’s Republic of China; 4School of Clinical Medicine, Southwest Medical University, Lu Zhou, Sichuan, People’s Republic of China*These authors contributed equally to this workCorrespondence: DongXia Zhai, Department of Gynecology of Traditional Chinese Medicine, Changhai Hospital, Naval Medical University, No. 168 Changhai Road, Shanghai, 200433, People’s Republic of China, Email [email protected] Ling Zhou, Department of Gynecology of Traditional Chinese Medicine, Changhai Hospital, Naval Medical University, No. 110 Ganhe Road, Shanghai, People’s Republic of China, Email [email protected]: 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.Keywords: polycystic ovary syndrome, insulin resistance, gut microbiota, metabolism