Department of Biology, San Diego State University, San Diego, California.
Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Diego, La Jolla, California.
Endocrinology. 2019 May 1;160(5):1193-1204. doi: 10.1210/en.2019-00050.
Polycystic ovary syndrome (PCOS) is a common endocrine disorder affecting ∼10% to 15% of reproductive-aged women worldwide. Diagnosis requires two of the following: hyperandrogenism, oligo-ovulation or anovulation, and polycystic ovaries. In addition to reproductive dysfunction, many women with PCOS display metabolic abnormalities associated with hyperandrogenism. Recent studies have reported that the gut microbiome is altered in women with PCOS and rodent models of the disorder. However, it is unknown whether the gut microbiome plays a causal role in the development and pathology of PCOS. Given its potential role, we hypothesized that exposure to a healthy gut microbiome would protect against development of PCOS. A cohousing study was performed using a letrozole-induced PCOS mouse model that recapitulates many reproductive and metabolic characteristics of PCOS. Because mice are coprophagic, cohousing results in repeated, noninvasive inoculation of gut microbes in cohoused mice via the fecal-oral route. In contrast to letrozole-treated mice housed together, letrozole mice cohoused with placebo mice showed significant improvement in both reproductive and metabolic PCOS phenotypes. Using 16S rRNA gene sequencing, we also observed that the overall composition of the gut microbiome and the relative abundance of Coprobacillus and Lactobacillus differed in letrozole-treated mice cohoused with placebo mice compared with letrozole mice housed together. These results suggest that dysbiosis of the gut microbiome may play a causal role in PCOS and that modulation of the gut microbiome may be a potential treatment option for PCOS.
多囊卵巢综合征（PCOS）是一种常见的内分泌疾病，影响全球约 10%至 15%的育龄妇女。诊断需要满足以下两个条件之一：高雄激素血症、排卵障碍或无排卵，以及多囊卵巢。除了生殖功能障碍外，许多患有 PCOS 的女性还表现出与高雄激素血症相关的代谢异常。最近的研究报告称，多囊卵巢综合征患者和该疾病的啮齿动物模型的肠道微生物组发生了改变。然而，尚不清楚肠道微生物组是否在 PCOS 的发展和病理中起因果作用。鉴于其潜在作用，我们假设暴露于健康的肠道微生物组将预防 PCOS 的发展。使用来曲唑诱导的 PCOS 小鼠模型进行了共栖研究，该模型再现了 PCOS 的许多生殖和代谢特征。由于小鼠是食粪动物，因此共栖会通过粪便-口腔途径在共栖小鼠中重复进行非侵入性的肠道微生物接种。与共同饲养的来曲唑处理的小鼠相比，与安慰剂小鼠共栖的来曲唑处理的小鼠的 PCOS 生殖和代谢表型均显著改善。使用 16S rRNA 基因测序，我们还观察到与共同饲养的来曲唑处理的小鼠相比，与安慰剂小鼠共栖的来曲唑处理的小鼠的肠道微生物组的整体组成和 Coprobacillus 和 Lactobacillus 的相对丰度存在差异。这些结果表明，肠道微生物组的失调可能在 PCOS 中起因果作用，并且调节肠道微生物组可能是 PCOS 的一种潜在治疗选择。
