Intestinal flora is a key factor in insulin resistance and contribute to the development of polycystic ovary syndrome and ameliorates glucose metabolism via activation of intestinal farnesoid X receptor (Human)

Polycystic ovary syndrome (PCOS) is a common gynecological endocrine disease and was reported to be affected by the gut microbiome dysbiosis. We recruited treatment-naïve PCOS patients and hormonally healthy controls and found that the abundance of Bacteroides increased significantly in treatment-naïve PCOS, and the dysbiosis patterns could be modeled by machine learning to diagnose treatment-naïve PCOS. The increase of Bacteroides in PCOS was reproduced in mice PCOS models induced by letrozole (LET), along with increased cecal farnesol. Removing gut microbiota ameliorated PCOS phenotype, insulin resistance and glucose metabolism and increased the relative mRNA levels of farnesoid X receptor (FXR) in the ileum and serum and serum fibroblast growth factor 15 (FGF15). Nevertheless, transplantation of PCOS human stool into mice did not induce PCOS but showed insulin resistance at ten weeks. Treating PCOS mice model with FXR agonist chenodeoxycholic acid (CDCA) can improve glucose metabolism.

多囊卵巢综合征（Polycystic ovary syndrome, PCOS）是一类常见的妇科内分泌疾病，现有研究表明其发病与肠道菌群失调（gut microbiome dysbiosis）存在关联。本研究招募了未经治疗的PCOS患者与激素水平健康的对照个体，发现未经治疗的PCOS患者体内拟杆菌属（Bacteroides）的丰度显著升高，且可通过机器学习构建菌群失调模型以诊断未经治疗的PCOS。PCOS患者体内拟杆菌属丰度升高的现象在来曲唑（letrozole, LET）诱导的小鼠PCOS模型中得到重现，该模型小鼠的盲肠法尼醇水平亦同步升高。清除肠道菌群可改善PCOS表型、胰岛素抵抗与糖代谢异常，并提升回肠、血清中法尼醇X受体（farnesoid X receptor, FXR）的mRNA相对表达水平以及血清成纤维细胞生长因子15（fibroblast growth factor 15, FGF15）的含量。不过，将PCOS患者的人类粪便移植至小鼠体内并未诱导出PCOS表型，但在移植10周后小鼠出现了胰岛素抵抗。采用法尼醇X受体激动剂鹅去氧胆酸（chenodeoxycholic acid, CDCA）处理PCOS小鼠模型，可改善其糖代谢水平。