北京大学第三医院乔杰研究组和北京大学基础医学院姜长涛研究组，合作揭示了肠微生物-胆汁酸-白介素-22信号轴在多囊卵巢综合征中的作用。2019年8月出版的《自然—医学》发表了这项成果。

研究人员希望了解肠道微生物群及其代谢产物对PCOS相关卵巢功能障碍和胰岛素抵抗的调节作用。研究人员发现，在PCOS患者的肠道微生物群中，普通拟杆菌（Bacteroides vulgatus）显著升高，同时伴随着甘氨脱氧胆酸和牛磺熊去氧胆酸水平的降低。来自患有PCOS女性的粪便微生物群移植或普通拟杆菌定植的受体小鼠会产生卵巢功能的紊乱、胰岛素抗性、胆汁酸代谢改变、白细胞介素-22分泌减少和不育。在机制上，甘氨脱氧胆酸通过GATA结合蛋白3引起肠道3型天然淋巴样细胞IL-22的分泌，而IL-22反过来改善PCOS表型。这一发现与PCOS患者中IL-22水平低是一致的。该研究表明，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PCOS的治疗有价值。

据了解，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，并且通常伴有胰岛素抵抗。PCOS中排卵功能障碍和胰岛素抵抗的机制仍然难以捉摸，因此限制了相关治疗的发展。代谢健康的改善与相对较高的微生物群基因含量和增加的微生物多样性有关。

更多阅读：

乔杰

乔杰，医学博士，教授，博士生导师，主任医师，中国工程院院士。现任北京大学第三医院院长，妇产科、生殖医学中心主任。作为世界最大疑难不孕诊治中心和国家自然科学基金委创新群体的带头人，乔杰建立了临床与基础多学科交叉的团队，带领团队年诊治国内外不孕患者近60万人次、实施辅助生殖技术手术3万余例，使中国大陆首例试管婴儿诞生地发展成为国际领先的生殖健康研究与培训基地。（据北京大学第三医院）

姜长涛

姜长涛，北京大学基础医学院生理学与病理生理学系研究员，博士生导师。研究方向为基于功能代谢组学探讨代谢性疾病发病机制及其药物靶点。（据北京大学基础医学院）

附：英文原文

Title: Gut microbiota–bile acid–interleukin-22 axis orchestrates polycystic ovary syndrome

Author: Xinyu Qi, Chuyu Yun, Lulu Sun, Jialin Xia, Qing Wu, Ying Wang, Lina Wang, Yangming Zhang, Xianyi Liang, Liying Wang, Frank J. Gonzalez, Andrew D. Patterson, Huiying Liu, Liangshan Mu, Zehong Zhou, Yue Zhao, Rong Li, Ping Liu, Chao Zhong, Yanli Pang, Changtao Jiang, Jie Qiao

Issue&Volume: Volume 25 Issue 8, August 2019

Abstract: Polycystic ovary syndrome (PCOS) is characterized by androgen excess, ovulatory dysfunction and polycystic ovaries1, and is often accompanied by insulin resistance2. 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 diversity3,4. 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.

DOI: 10.1038/s41591-019-0509-0

Source::https://www.nature.com/articles/s41591-019-0509-0