Antibiotic Therapy and Vaginal Microbiota Transplantation Reduce Endometriosis Disease Progression in Female Mice via NF-κB Signaling Pathway

Abstract

Endometriosis (EMS) is a disease characterized by estrogen-dependent, chronic inflammatory, and annoying symptoms, which inflicts about 10% reproductive-age women. The diagnosis of endometriosis mainly depends on pathological examination after surgical resection while the pathogenesis of EMS is not clear enough. Surgical resection and drug therapy (including painkillers and hormone therapy, especially gonadotropin-releasing hormone analogs, GnRH-a) are widely used, but they are expensive and have many side effects. There are few studies on vaginal microorganisms in women with endometriosis. We collected vaginal secretions from women with EMS confirmed by pathology and demonstrated that they were different from that of healthy women by 16s rRNA high-throughput sequencing. Additionally, we established the EMS model in female mice by intraperitoneally injecting fragments from donor mice (3-week growth). Then, the mice were treated with mixed antibiotics (vagina) and NF-κB signaling pathway inhibitors (intraperitoneal injection), respectively. The result suggested that the ectopic lesions were inhibited. In addition, inflammatory cytokines IL-1β, IL-6, and TNF-α in peritoneal fluid, cell proliferation marker ki-67, and macrophage marker Iba-1 in ectopic lesions decreased significantly from that of mock mice. We also observed similar results as above by vaginal microbiota transplantation (VMT) and subcutaneous injection of leuprorelin acetate (LA, one of GnRH-a) for mice with EMS. These results showed that vaginal use of antibiotics or VMT is helpful to treat endometriosis in mice. However, due to the great difference between human and mouse vaginal microbiota, its mechanism and clinical transformation application still need to be further studied in the future.

Female reproductive dysfunctions and the gut microbiota

“…However, enrichment of Gardnerella was seen in both endometriosis and infertility (Wee et al 2018, Ata et al 2019. Further, the study of vaginal microbiota in healthy controls (n = 18) and endometriosis patients (n = 16) also found a significant enrichment of Atopobium as well as Gardnerella, while Lactobacillus was found to be lower in patients with endometriosis (Lu et al 2022). Similarly, the decrease in the Lactobacillus level of the vaginal microbiome was highlighted in the patient with endometriosis (Wei et al 2020).…”

The effect of broccoli extract and soy isoflavones on endometrial implants and oxidative parameters in female rat model of endometriosis

“…The current ndings showed no signi cant effects of the studied treatments on MDA. Previous studies have represented that the volume of endometriosis lesions was signi cantly decreased simultaneously with a reduction in the level of IL-6, TNF-α, estradiol and vascular endothelial growth factor (VEGF) within serum and peritoneal uid [35]. It has been corroborated that dietary supplements including sulforaphane and iso avones decrease the levels of anti-in ammatory cytokines such as TNF-α and nuclear factor kappa B (NF-κB), that are involved in the mechanism of in ammation [36,37].…”

Endometriosis as an Infectious Disease: Association with Chronic Endometritis

“…Interestingly, oral administration of feces from mice with endometriosis exacerbates the growth and inflammation of the endometriotic lesions in metronidazole-treated mice, indicating a key role of gut bacteria in the promotion and progression of endometriosis in these mice. Furthermore, Lu et al [65] reported the effectiveness of the vaginal administration of the VNMA mixture (once every 3 days for 21 days) via an absorbable gel sponge on endometriosis lesions. While the disorder of the vaginal microbiota potentially promoted the progression of endometriosis, antibiotic treatment was capable of reducing the volume of the endometriotic lesions via regulation of the nuclear factor-kappa B signaling pathway.…”