Depletion of gut microbiota influents glucose metabolism and hyperandrogenism traits of mice with PCOS induced by letrozole

作者：Yushan Li, Yuchen Zhu, Dan Li, Wen Liu, Yi Zhang, Wei Liu, Chenhong Zhang, Tao Tao · 发表于：Frontiers in Endocrinology · 年份：2023 · DOI：10.3389/fendo.2023.1265152 · 被引用次数：23 · 研究领域：Ovarian function and disorders、Gut microbiota and health、Reproductive tract infections research

Background: Polycystic ovary syndrome (PCOS) is a multifaceted disorder that impacts metabolism, reproduction, as well as endocrine function, characterized by excessive levels of androgen and insulin resistance. The gut microbiota has been implicated in the pathogenesis of PCOS. However, the precise mechanisms through which the gut microbiota influences PCOS still require further elucidation. Methods: The PCOS mouse model was established through the administration of letrozole to both conventional and antibiotics-treated mice. The evaluation of glucose metabolism, sex hormone levels, and ovarian morphology was conducted. Furthermore, the fecal samples from each group of mice were subjected to 16S rRNA gene sequencing, and functional prediction of gut microbiota was proceeded using PICRUSt2 to explore potential mechanisms. Results: By using letrozole-induced PCOS mice model, we manifested that antibiotic intervention significantly reduced the serum total testosterone level and ameliorated glucose intolerance. Antibiotic treatment reduced the number of amplicon sequence variants (ASVs), as well as the Shannon and Simpson index. Meanwhile, letrozole induced a significant increase in the Shannon and Simpson index instead of ASVs. Through random forest model analysis, the results revealed significant alterations in three distinct groups of microbiota, namely Clostridia_vadinBB60_group, Enterorhabdus, and Muribaculaceae after letrozole treatment. Further correlation analysis reveal...