Department of Obstetrics and Gynecology, Center for Obesity and Metabolic Disease Research, School of Basic Medical Sciences, Third Hospital, Peking University, Beijing, China.
Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University, and the Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, China.
Nat Med. 2019 Aug;25(8):1225-1233. doi: 10.1038/s41591-019-0509-0. Epub 2019 Jul 22.
Polycystic ovary syndrome (PCOS) is characterized by androgen excess, ovulatory dysfunction and polycystic ovaries, and is often accompanied by insulin resistance. The mechanism of ovulatory dysfunction and insulin resistance in PCOS remains elusive, thus limiting the development of therapeutics. Improved metabolic health is associated with a relatively high microbiota gene content and increased microbial diversity. This study aimed to investigate the impact of the gut microbiota and its metabolites on the regulation of PCOS-associated ovarian dysfunction and insulin resistance. Here, we report that Bacteroides vulgatus was markedly elevated in the gut microbiota of individuals with PCOS, accompanied by reduced glycodeoxycholic acid and tauroursodeoxycholic acid levels. Transplantation of fecal microbiota from women with PCOS or B. vulgatus-colonized recipient mice resulted in increased disruption of ovarian functions, insulin resistance, altered bile acid metabolism, reduced interleukin-22 secretion and infertility. Mechanistically, glycodeoxycholic acid induced intestinal group 3 innate lymphoid cell IL-22 secretion through GATA binding protein 3, and IL-22 in turn improved the PCOS phenotype. This finding is consistent with the reduced levels of IL-22 in individuals with PCOS. This study suggests that modifying the gut microbiota, altering bile acid metabolism and/or increasing IL-22 levels may be of value for the treatment of PCOS.
多囊卵巢综合征（PCOS）的特征是雄激素过多、排卵功能障碍和多囊卵巢，常伴有胰岛素抵抗。PCOS 患者排卵功能障碍和胰岛素抵抗的机制仍不清楚，从而限制了治疗方法的发展。改善代谢健康与相对较高的微生物组基因含量和增加的微生物多样性有关。本研究旨在探讨肠道微生物群及其代谢产物对调节 PCOS 相关卵巢功能障碍和胰岛素抵抗的影响。在这里，我们报告说，脆弱拟杆菌在 PCOS 患者的肠道微生物群中明显升高，伴随着甘氨脱氧胆酸和牛磺脱氧胆酸水平降低。来自 PCOS 女性或脆弱拟杆菌定植的受体小鼠的粪便微生物群移植导致卵巢功能破坏增加、胰岛素抵抗、胆汁酸代谢改变、白细胞介素-22 分泌减少和不孕。从机制上讲，甘氨脱氧胆酸通过 GATA 结合蛋白 3诱导肠道第三组固有淋巴细胞 IL-22 的分泌，而 IL-22 反过来又改善了 PCOS 表型。这一发现与 PCOS 患者 IL-22 水平降低相一致。这项研究表明，改变肠道微生物群、改变胆汁酸代谢和/或增加 IL-22 水平可能对治疗 PCOS 有价值。
