Association between Polycystic Ovary Syndrome and Gut Microbiota

Abstract

Polycystic ovary syndrome (PCOS) is the most frequent endocrinopathy in women of reproductive age. It is difficult to treat PCOS because of its complex etiology and pathogenesis. Here, we characterized the roles of gut microbiota on the pathogenesis and treatments in letrozole (a nonsteroidal aromatase inhibitor) induced PCOS rat model. Changes in estrous cycles, hormonal levels, ovarian morphology and gut microbiota by PCR-DGGE and real-time PCR were determined. The results showed that PCOS rats displayed abnormal estrous cycles with increasing androgen biosynthesis and exhibited multiple large cysts with diminished granulosa layers in ovarian tissues. Meanwhile, the composition of gut microbiota in letrozole-treated rats was different from that in the controls. Lactobacillus, Ruminococcus and Clostridium were lower while Prevotella was higher in PCOS rats when compared with control rats. After treating PCOS rats with Lactobacillus and fecal microbiota transplantation (FMT) from healthy rats, it was found that the estrous cycles were improved in all 8 rats in FMT group, and in 6 of the 8 rats in Lactobacillus transplantation group with decreasing androgen biosynthesis. Their ovarian morphologies normalized. The composition of gut microbiota restored in both FMT and Lactobacillus treated groups with increasing of Lactobacillus and Clostridium, and decreasing of Prevotella. These results indicated that dysbiosis of gut microbiota was associated with the pathogenesis of PCOS. Microbiota interventions through FMT and Lactobacillus transplantation were beneficial for the treatments of PCOS rats.

Prenatal androgen exposure causes hypertension and gut microbiota dysbiosis

“…42 , 77 PCOS has been linked to metabolic syndrome particularly insulin resistance 78 and hypertension. 79 −82 When a pregnant mother with PCOS is subsequently diagnosed with hyperinsulinemia, hypertension, or hyperandrogenemia during pregnancy this increases maternal and fetal morbidity and mortality.…”

“…In letrozole-induced PCOS models, gut microbiota exhibited a deficiency in bacteria from the genera Clostridium, Lactobacillus, Ruminococcus but an enrichment of Prevotella with no differences observed in bacteria from Bifidobacterium, Enterococcus , and Bacteroides . 42 Another letrozole-induced PCOS model displayed an increase in bacteria of the genera Alistipes, Allobaculum, Blautia , and Ruminococcaceae . 35 Neonatal exposure to a single-injection of testosterone increased the concentration of Ruminococcus and Coprococcus —two bacteria involved in bile acid synthesis and found to be increased in the gut of prediabetics.…”

“…33 , 42 Administration of Akkermansia as a probiotic was shown to improve the intestinal barrier of the gut by increasing the expression of mucin 2 within the colon. 126 A decreased abundance of Akkermansia within the colon of PCOS patients and our prenatal androgen model may be associated with impaired mucosal maintenance.…”

“…In an aromatase inhibitor-induced PCOS model, fecal microbial transplant from control animals alleviated symptoms associated with androgenization such as acyclicity, weight gain, and hyperleptinemia in adult rats. 42 Therefore, understanding the origins of dysbiosis in PCOS may be crucial to preventing and treating this disorder.…”

Alterations in Gut Microbiome Composition and Barrier Function Are Associated with Reproductive and Metabolic Defects in Women with Polycystic Ovary Syndrome (PCOS): A Pilot Study

“…In 2012, Tremellen and Pearce postulated the hypothesis that diet-induced gut bacterial dysbiosis and subsequent gut barrier dysfunction and endotoxemia may drive the chronic inflammation and subsequent insulin resistance and androgen hypersecretion associated with PCOS [18]. To date, no published data on the gut microbiome in human PCOS patients exist, though there have been recent reports of alterations in the fecal microbiome in PCOS rodent models [19,20]. Data on gut permeability in PCOS patients are likewise scarce, though an increase in serum zonulin, a regulator of tight junction function, has been reported [21].…”