Polycystic ovary syndrome (PCOS) is a common endocrine disease in females that is characterized by hyperandrogenemia, chronic anovulation, and polycystic ovaries. However, the exact etiology and pathogenesis of PCOS are still unknown. The aim of this study was to clarify the bacterial, stress status, and metabolic differences in the gut microbiomes of healthy individuals and patients with high body mass index (BMI) PCOS (PCOS-HB) and normal BMI PCOS (PCOS-LB), respectively. Here, we compared the gut microbiota characteristics of PCOS-HB, PCOS-LB, and healthy controls by 16S rRNA gene sequencing, FK506-binding protein 5 (FKBP5) DNA methylation and plasma metabolite determination. Clinical parameter comparisons indicated that PCOS patients had higher concentrations of total testosterone, androstenedione, dehydroepiandrosterone sulfate, luteinizing hormone, and HOMA-IR while lower FKBP5 DNA methylation. Significant differences in bacterial diversity and community were observed between the PCOS and healthy groups but not between the PCOS-HB and PCOS-LB groups. Bacterial species number was negatively correlated with insulin concentrations (both under fasting status and 120 min after glucose load) and HOMA-IR but positively related to FKBP5 DNA methylation. Compared to the healthy group, both PCOS groups had significant changes in bacterial genera, including Prevotella_9, Dorea, Maihella, and Slackia, and plasma metabolites, including estrone sulfate, lysophosphatidyl choline 18:2, and phosphatidylcholine (22:6e/19:1). The correlation network revealed the complicated interaction of the clinical index, bacterial genus, stress indices, and metabolites. Our work links the stress responses and gut microbiota characteristics of PCOS disease, which might afford perspectives to understand the progression of PCOS.

多囊卵巢综合征（PCOS）是女性常见的内分泌疾病，以高雄激素血症、慢性无排卵和多囊卵巢为特征。然而，PCOS的确切病因和发病机制仍不清楚。本研究的目的是阐明健康个体和高体重指数 (BMI) PCOS (PCOS-HB) 和正常 BMI PCOS (PCOS-LB) 患者肠道微生物组的细菌、压力状态和代谢差异，分别。在这里，我们通过 16S rRNA 基因测序、FK506 结合蛋白 5 (FKBP5) DNA 甲基化和血浆代谢物测定比较了 PCOS-HB、PCOS-LB 和健康对照的肠道微生物群特征。临床参数比较表明，PCOS 患者的总睾酮、雄烯二酮、硫酸脱氢表雄酮、黄体生成素和 HOMA-IR，同时降低 FKBP5 DNA 甲基化。在 PCOS 组和健康组之间观察到细菌多样性和群落的显着差异，但在 PCOS-HB 和 PCOS-LB 组之间没有观察到。细菌种类数与胰岛素浓度（空腹状态和葡萄糖负荷后 120 分钟）和 HOMA-IR 呈负相关，但与 FKBP5 DNA 甲基化呈正相关。与健康组相比，两个 PCOS 组的细菌属都发生了显着变化，包括 细菌种类数与胰岛素浓度（空腹状态和葡萄糖负荷后 120 分钟）和 HOMA-IR 呈负相关，但与 FKBP5 DNA 甲基化呈正相关。与健康组相比，两个 PCOS 组的细菌属都发生了显着变化，包括 细菌种类数与胰岛素浓度（空腹状态和葡萄糖负荷后 120 分钟）和 HOMA-IR 呈负相关，但与 FKBP5 DNA 甲基化呈正相关。与健康组相比，两个 PCOS 组的细菌属都发生了显着变化，包括普雷沃_9，Dorea，Maihella，和的Slackia，和血浆代谢物，包括硫酸雌酮，溶血磷脂酰胆碱18：2，和磷脂酰胆碱（22：6E / 19：1）。相关网络揭示了临床指标、细菌属、应激指标和代谢物之间复杂的相互作用。我们的工作将 PCOS 疾病的压力反应和肠道微生物群特征联系起来，这可能为了解 PCOS 的进展提供新的视角。