Oligofructose alleviates hyperandrogenism in polycystic ovary syndrome through gut microbiota-derived bile acids

作者：Yuhui Wang, Xitong Liu, Zhi Li, Ahui Kang, Yixuan Bai, Yang Wang, Yan Liu, Chujun Zhang, Jiaqi Yang, Qingqing Cai, Yi Feng, Huan Yi, Mengyu Zhang, Feifei Zhang, Haiou Liu, Congjian Xu · 发表于：Journal of Advanced Research · 年份：2026 · DOI：10.1016/j.jare.2026.04.036 · 被引用次数：2 · 研究领域：Gut microbiota and health、Ovarian function and disorders、Liver Disease Diagnosis and Treatment

INTRODUCTION: Polycystic ovary syndrome (PCOS) is a common endocrine disorder in reproductive-age women, characterized by hyperandrogenism and metabolic dysfunction. Dietary interventions are recommended as one of the first-line therapies. Oligofructose (OFS), a prebiotic fiber, has demonstrated clinical benefits in PCOS; however, its underlying mechanism remains unclear. OBJECTIVES: To determine whether OFS alleviates PCOS-like phenotypes through bile acid-dependent mechanisms and to identify downstream ovarian steroidogenic responses. METHODS: Letrozole-induced PCOS-like mice received OFS supplementation. Microbiota dependence was assessed using antibiotic depletion and fecal microbiota transplantation. Bile acid involvement was evaluated using cholestyramine. Gut microbial composition and function were profiled by 16S rRNA and metagenomic sequencing, and bile acids were quantified by UHPLC-MS/MS. Ovarian transcriptomics, ex vivo ovarian explants, and primary granulosa cells were used to examine steroidogenic changes, with pharmacological inhibition applied to assess TGR5-related signaling. RESULTS: OFS improved reproductive and metabolic abnormalities in PCOS-like mice. These benefits were abolished by microbiota depletion and bile acid sequestration, indicating microbiota- and bile acid-dependent effects. OFS was associated with increased circulating hyodeoxycholic acid (HDCA), which negatively correlated with serum testosterone. HDCA supplementation partially reproduced ...