多囊卵巢综合征子宫内膜功能障碍的微生物与代谢关联：一项转化研究
该项前瞻性队列研究纳入110名PCOS女性和110名年龄、BMI匹配的对照，探究肠道菌群失调与代谢紊乱对子宫内膜功能及妊娠结局的影响。结果显示PCOS女性流产率显著升高，伴Parabacteroides merdae丰度降低及血清支链氨基酸（尤其是异亮氨酸）升高。机制实验提示P.merdae耗竭与异亮氨酸累积可能通过诱导子宫内膜衰老增加流产风险。
要点
- PCOS女性流产率显著高于对照，且肠道P.merdae丰度明显减少。
- 血清异亮氨酸升高可剂量依赖性诱导人子宫内膜基质细胞衰老。
- 恢复P.merdae水平降低血清异亮氨酸，改善子宫内膜衰老表型并减少大鼠胚胎吸收率。
核心结论
- P.merdae耗竭与异亮氨酸累积可能关联子宫内膜衰老和流产风险增加，提示肠道微生物-代谢物通路参与PCOS相关生殖功能障碍。
研究设计与样本
- 前瞻性队列研究，整合机制实验，于浙江大学医学院附属妇产科医院进行（2022–2024）。
- 共纳入110名PCOS女性和110名年龄、BMI匹配的对照。
- 方法包括16S rRNA和宏基因组测序、非靶向和靶向血清代谢组学，以及原代子宫内膜基质细胞和PCOS大鼠模型的功能验证。
主要发现
- PCOS女性流产率显著高于对照。
- PCOS女性显示P.merdae丰度显著减少，血清支链氨基酸（尤其是异亮氨酸）水平升高。
- 外源性异亮氨酸以剂量依赖性方式诱导人子宫内膜基质细胞衰老。
关键数值与推荐
- 流产率：PCOS组显著高于对照组（具体数值未提供）。
- P.merdae丰度：PCOS组显著降低（具体数值未提供）。
- 血清异亮氨酸水平：PCOS组显著升高（具体数值未提供）。
临床怎么用
- 检测PCOS患者肠道P.merdae丰度和血清异亮氨酸水平，可能有助于识别流产高危人群。
- 补充P.merdae或调节异亮氨酸代谢可能成为改善PCOS子宫内膜功能和妊娠结局的新策略。
局限性
- 样本来源单一中心，可能限制外推性。
- 动物和细胞实验结果不能直接等同于人体效应。
以上解读依据论文摘要（全文未开放获取或许可不允许翻译转载）。
原文
ABSTRACT Objective Women with polycystic ovary syndrome (PCOS) exhibit a substantially increased risk of miscarriage, yet the underlying mechanisms remain inadequately understood. This study aimed to investigate whether specific gut microbial dysbiosis and metabolic disturbance are associated with and may potentially contribute to endometrial dysfunction and adverse pregnancy outcomes in women with PCOS. Design Prospective cohort study integrated with mechanistic experiments. Setting Women's Hospital, School of Medicine, Zhejiang University, China (2022–2024). Population A total of 110 women with PCOS and 110 age- and body mass index-matched controls were enrolled. Methods We performed 16S rRNA and metagenomic sequencing of gut microbiota, with untargeted and targeted serum metabolomics. Functional validation was conducted using primary human endometrial stromal cells and a PCOS rat model intervened with Parabacteroides merdae (P. merdae) supplementation or faecal microbiota transplantation. Main Outcome Measures Gut microbiota composition, serum metabolites, endometrial senescence markers, and pregnancy outcomes. Results Women with PCOS exhibited significantly higher miscarriage rates than controls, accompanied by a marked depletion of P. merdae abundance and elevated serum levels of branched-chain amino acids, particularly isoleucine. Exogenous isoleucine induced cellular senescence in human endometrial stromal cells in a dose-dependent manner. Restoration of P. merdae levels in the PCOS rat model resulted in decreased serum isoleucine levels, amelioration of the senescent endometrial phenotype, and reduction in the fetal resorption rate. Conclusions These findings suggest that P. merdae depletion and the concurrent accumulation of isoleucine may be associated with endometrial senescence and elevated risk of miscarriage, suggesting the possible involvement of a gut microbiota–metabolite pathway in PCOS-related reproductive dysfunction. These results also provide a mechanistic basis for future translational investigations.
引用
- BJOG：Microbial and Metabolic Correlates of Endometrial Dysfunction in Polycystic Ovary Syndrome: A Translational Study
供执业医师工作参考，不替代临床判断；数值与分级以指南原文为准。