Gut microbiota dysbiosis in polycystic ovary syndrome: Mechanisms of progression and clinical applications.

Polycystic ovary syndrome (PCOS) is the most common endocrine diseases in women of childbearing age that leads to menstrual disorders and infertility. The pathogenesis of PCOS is complex and has not yet been fully clarified. Gut microbiota is associated with disorders of lipid, glucose, and steroid hormone metabolish. A large body of studies demonstrated that gut microbiota could regulate the synthesis and secretion of insulin, and affect androgen metabolism and follicle development, providing us a novel idea for unravelling the pathogenesis of PCOS. The relationship between gut microbiota and the pathogenesis of PCOS is particularly important. This study reviewed recent research advances in the roles of gut microbiota in the occurrence and development of PCOS. It is expected to provide a new direction for the treatment of PCOS based on gut microbiota.

Sun Y ，Gao S ，Ye C ，Zhao W ... -  《Frontiers in Cellular and Infection Microbiology》

A New Approach to Polycystic Ovary Syndrome: The Gut Microbiota.

Yurtdaş G ，Akdevelioğlu Y 《-》

Effects of gut microbiota on omega-3-mediated ovary and metabolic benefits in polycystic ovary syndrome mice.

Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disorder that frequently exhibits low-grade inflammation, pro-oxidant activity, and gut dysbiosis. PCOS has become one of the leading causes of female infertility worldwide. Recently, omega-3 polyunsaturated fatty acids (PUFAs) have been proven to benefit metabolic disorders in PCOS patients. However, its roles in the regulation of metabolic and endocrinal balances in PCOS pathophysiology are not clear. In the present study, we aimed to explore how omega-3 PUFAs alleviate ovarian dysfunction and insulin resistance in mice with dehydroepiandrosterone (DHEA)-induced PCOS by modulating the gut microbiota. We induced PCOS in female mice by injecting them with DHEA and then treated them with omega-3 PUFAs. 16S ribosomal DNA (rDNA) amplicon sequencing, fecal microbiota transplantation (FMT) and antibiotic treatment were used to evaluate the role of microbiota in the regulation of ovarian functions and insulin resistance (IR) by omega-3 PUFAs. To further investigate the mechanism of gut microbiota on omega-3-mediated ovarian and metabolic protective effects, inflammatory and oxidative stress markers in ovaries and thermogenic markers in subcutaneous and brown adipose tissues were investigated. We found that oral supplementation with omega-3 PUFAs ameliorates the PCOS phenotype. 16S rDNA analysis revealed that omega-3 PUFA treatment increased the abundance of beneficial bacteria in the gut, thereby alleviating DHEA-induced gut dysbiosis. Antibiotic treatment and FMT experiments further demonstrated that the mechanisms underlying omega-3 benefits likely involve direct effects on the ovary to inhibit inflammatory cytokines such as IL-1β, TNF-α and IL-18. In addition, the gut microbiota played a key role in the improvement of adipose tissue morphology and function by decreasing multilocular cells and thermogenic markers such as Ucp1, Pgc1a, Cited and Cox8b within the subcutaneous adipose tissues. These findings indicate that omega-3 PUFAs ameliorate androgen-induced gut microbiota dysbiosis. The gut microbiota plays a key role in the regulation of omega-3-mediated IR protective effects in polycystic ovary syndrome mice. Moreover, omega-3 PUFA-regulated improvements in the ovarian dysfunction associated with PCOS likely involve direct effects on the ovary to inhibit inflammation. Our findings suggest that omega-3 supplementation may be a promising therapeutic approach for the treatment of PCOS by modulating gut microbiota and alleviating ovarian dysfunction and insulin resistance.

Zhang H ，Zheng L ，Li C ，Jing J ，Li Z ，Sun S ，Xue T ，Zhang K ，Xue M ，Cao C ，Ouyang L ，Qian Z ，Xu R ，He Z ，Ma R ，Chen L ，Yao B ... -  《Journal of Ovarian Research》

Present and Future: Crosstalks Between Polycystic Ovary Syndrome and Gut Metabolites Relating to Gut Microbiota.

Polycystic ovary syndrome (PCOS) is a common disease, affecting 8%-13% of the females of reproductive age, thereby compromising their fertility and long-term health. However, the pathogenesis of PCOS is still unclear. It is not only a reproductive endocrine disease, dominated by hyperandrogenemia, but also is accompanied by different degrees of metabolic abnormalities and insulin resistance. With a deeper understanding of its pathogenesis, more small metabolic molecules, such as bile acids, amino acids, and short-chain fatty acids, have been reported to be involved in the pathological process of PCOS. Recently, the critical role of gut microbiota in metabolism has been focused on. The gut microbiota-related metabolic pathways can significantly affect inflammation levels, insulin signaling, glucose metabolism, lipid metabolism, and hormonal secretions. Although the abnormalities in gut microbiota and metabolites might not be the initial factors of PCOS, they may have a significant role in the pathological process of PCOS. The dysbiosis of gut microbiota and disturbance of gut metabolites can affect the progression of PCOS. Meanwhile, PCOS itself can adversely affect the function of gut, thereby contributing to the aggravation of the disease. Inhibiting this vicious cycle might alleviate the symptoms of PCOS. However, the role of gut microbiota in PCOS has not been fully explored yet. This review aims to summarize the potential effects and modulative mechanisms of the gut metabolites on PCOS and suggests its potential intervention targets, thus providing more possible treatment options for PCOS in the future.

Zhang M ，Hu R ，Huang Y ，Zhou F ，Li F ，Liu Z ，Geng Y ，Dong H ，Ma W ，Song K ，Song Y ... -  《Frontiers in Endocrinology》

Exploration of the pathogenesis of polycystic ovary syndrome based on gut microbiota: A review.

Guo H ，Luo J ，Lin H 《-》