Naringenin, a Flavonoid, Modulates Gut Microbiome and Ameliorates Hormone Levels to Improve Polycystic Ovary Syndrome in Letrozole-induced Rats 

Abstract Background: Polycystic ovary syndrome (PCOS) is a common female endocrinopathy, which severely affect the menstruation and fertility of patients. Naringenin, a natural flavanone, has emerged as a potential therapeutic agent for the management a variety of diseases. However, the underlying mechanism of naringenin in anti‑PCOS is unclear. This study was focused on investigating the effects of naringenin on body weight, ovarian tissue, serum hormone level, glucose metabolism level and gut microbiome in letrozole-induced PCOS model rats.Methods: First, we administered letrozole gavage to 10-week-old SD female rats for 4 weeks to induce PCOS rats model, the estrus cycle was observed through the vaginal smear of rats to determine the establishment successful of a PCOS rat model. Then, the successfully modeled PCOS rats were treated with naringenin for 2 months. Finally, observed the changes of rat body weight, ovarian tissue, serum hormone level, glucose metabolism level and gut microbiome after naringenin treatment. Results: The naringenin treatment ameliorate the hormone levels, such testosterone (T), estradiol (E2), follicle-stimulating hormone (FSH), luteinizing hormone (LH), improve insulin resistance and the ovarian tissue pathological changes, reduced body weight in the PCOS model rat. Meanwhile, through the detection of rDNA in the faeces of the PCOS model rat, we found some beneficial microbes such [Ruminococcus], Faecalibacterium, Butyricimonas, Lachnospira, Parabacteroides, Butyricicoccus and Roseburia were enrichment in naringenin group when compared with the PCOS rats. Conclusions: In summary, our results indicated that naringenin could play an anti-PCOS role, and its mechanism may be closely related to regulating the beneficial microbes of gut microbiome. Our research could provide a new perspective for the treatment of PCOS and its related disease.