Letrozole and the Traditional Chinese Medicine, Shaofu Zhuyu Decoction, Reduce Endometriotic Disease Progression in Rats: A Potential Role for Gut Microbiota.

Ying Cao,Yongsen Jia,Dingjie Xu,Chunhua Jiang,Yanyan Yu

doi:10.1155/2020/3687498

Abstract

We previously showed that the Chinese herbal medicine, Shaofu Zhuyu decoction (SFZYD), shrank the size of endometriotic lesions in rats with endometriosis. We therefore conducted the present study to investigate the effects of letrozole and SFZYD on gut microbiota in endometriotic rats. Rats were divided into four groups: a blank group, model group, letrozole group, and SFZY group. Ectopic lesion size and COX-2 expression in the endometrium and endometriotic lesions were compared, and the community of gut microbiota was detected using 16S rRNA gene sequencing. Both letrozole and SFZYD reduced the size of ectopic lesions as well as lowered the expression of COX-2, thus reducing the inflammatory response. Compared with the blank group, the α-diversity of gut microbiota in endometriotic rats decreased, the Firmicutes/Bacteroidetes ratio increased, and the abundance of Ruminococcaceae was reduced. The α-diversity of gut microbiota in the letrozole group was similar to that in the model group, but the Firmicutes/Bacteroidetes ratio was diminished. The α-diversity in the SFZY group was similar to that in the blank group, the Firmicutes/Bacteroidetes ratio was attenuated, and the abundance of Ruminococcaceae was elevated compared with the model group. These results indicated that the therapeutic mechanisms of both letrozole and SFZYD were related to the restoration of gut microbiota.

Highlights

Endometriosis (EMs) is an estrogen-dependent disease in which endometrial glands and stromal tissues are implanted outside the uterine cavity. e incidence of EMs is 10% in women of childbearing age and up to 30–45% in infertile women [1]. e primary manifestations include dysmenorrhea, chronic pelvic pain, and infertility that seriously affect the quality of life of patients
Our previous study showed that Shaofu Zhuyu decoction (SFZYD) inhibited cellular proliferation, promoted apoptosis, and reduced angiogenesis in ectopic endometrial tissues, playing a role in the treatment of endometriosis [18]. e purpose of the present study is to investigate our hypothesis that letrozole and SFZYD act on gut microbiota to inhibit the progression of lesions in rats with EMs
Yuan et al demonstrated that the Firmicutes/Bacteroidetes ratio was elevated in mice with endometriosis, as were the abundances of Firmicutes and Bacteroidetes in the gut microbiota flora of mice 42 days after modeled induction [15]; this is consistent with our study

Summary

Introduction

Endometriosis (EMs) is an estrogen-dependent disease in which endometrial glands and stromal tissues are implanted outside the uterine cavity. e incidence of EMs is 10% in women of childbearing age and up to 30–45% in infertile women [1]. e primary manifestations include dysmenorrhea, chronic pelvic pain, and infertility that seriously affect the quality of life of patients. Its arcane etiology is an important reason hindering research on treatment for EMs. According to the ectopic implantation theory accepted by most scholars, EMs originated from the shedding of endometrial debris that enters the pelvic cavity with countercurrent menstrual blood flow [2]. Investigators have demonstrated an increase in the number of activated macrophages and proinflammatory cytokines and angiogenic factors in the pelvic fluid of EMs patients [7, 8], which could provide a favorable environment for ectopic endometrial implantation [8]. Compared with normal pelvic fluid, the pelvic fluid in EMs patients promotes the expression of the vascular endothelial growth factor (VEGF) and urokinase plasminogen activator (uPA) in endometrial cells [9]. Lipopolysaccharide (LPS), a common endotoxin, is at a much higher concentration in the Evidence-Based Complementary and Alternative Medicine menstrual blood of EMs patients relative to women without EMs, and the combination of LPS and toll-like receptor 4 (TLR4) can promote the proliferation of eutopic endometrial stromal cells. e quantity of E. coli (i.e., the principal source of LPS in the menstrual blood of EMs patients) is much higher than that in the normal population [10]

Methods

Results

Conclusion