Integrated microbiome and metabolome analysis reveals that zishen qingre lishi huayu recipe regulates gut microbiota and butyrate metabolism to ameliorate polycystic ovary syndrome

Background: Polycystic ovary syndrome (PCOS) is a metabolic disorder disease strongly associated with gut microbiota (GM). Zishen Qingre Lishi Huayu recipe (ZQLHR), a traditional Chinese medicinal compound, has patented and shown therapeutic effects in treating PCOS in clinical trials without clear pharmacological mechanisms. This study aimed to disclose the potential therapeutic mechanism of ZQLHR on PCOS. Methods: We firstly confirmed the therapeutic effects of ZQLHR treatment in PCOS patients. 16S rRNA sequencing, untargeted metabolomics, fecal microbiota transplantation (FMT), high performance liquid chromatography (HPLC) and Person's correlation analysis were conducted to elucidate the potential therapeutic mechanism. Results: These results showed that PCOS symptoms in ZQLHR patients were significantly ameliorated. ZQLHR could increase the levels of butyrate-producing Lachnospira and Faecalibacterium and decrease the abundance of Escherichia-Shigella. Untargeted metabolomics showed that ZQLHR significantly improved host metabolic function, particularly butyrate metabolism and citrate cycle (TCA cycle) metabolism. The combined Faecalibacterium and butyrate metabolism datasets were correlated. Stool samples from ZQLHR patients could ameliorate ovarian architecture, significantly reduce testosterone (T), estradiol (E-2) and luteinizing hormone (LH) levels and increased follicle-stimulating hormone (FSH) levels and increase the content of butyric acid in PCOS mice (P < 0.01). Moreover, the correlation analysis showed that some biochemical parameters (T, E-2, LH levels and FSH) and butyric acid were correlated. Conclusion: We firstly depicted that ZQLHR could alleviate the series of symptom in women with PCOS by regulating gut microbiota and butyrate metabolism. This study provides a scientific basis and new ideas for the therapy of PCOS.