Molecular detection of intrauterine microbial colonization in women with endometriosis Original paper

What Was Studied?

This study investigated the molecular detection of intrauterine microbial colonization in women with and without endometriosis, utilizing a 16S rDNA metagenome assay to evaluate bacterial presence in endometrial swabs and cystic fluid samples. The primary aim was to explore the role of microbial colonization in the intrauterine environment and its potential contribution to endometriosis pathogenesis, especially in women treated with gonadotropin-releasing hormone agonist (GnRHa). The study compared microbial communities in both endometrial tissue and cystic fluid derived from ovarian endometrioma and non-endometrioma cysts. The analysis aimed to validate the “bacterial contamination hypothesis,” which posits that microbial colonization might exacerbate inflammatory responses, contributing to endometriosis progression.

Who Was Studied?

The study included 32 women with endometriosis and 32 women without endometriosis. Among these, half of each group (16 women) received GnRHa treatment for 4–6 months prior to sample collection. Endometrial swabs and cystic fluid samples were collected during laparoscopic procedures at Nagasaki University. Women were included if they were of reproductive age, with regular menstrual cycles, and had not taken antibiotics or immunosuppressants within three months prior to the study. The endometriosis cases were confirmed histologically, and cystic fluids were categorized as either ovarian endometrioma (OE) or non-endometrioma (NE) cysts. The study employed 16S rDNA metagenome sequencing using the Illumina MiSeq system to identify bacterial taxa.

What Were the Most Important Findings?

The study identified a significant alteration in the microbial landscape within the intrauterine environment and ovarian cystic fluid of women with endometriosis, particularly those undergoing GnRHa treatment. Notably, there was a significant decrease in Lactobacillaceae populations (p <0.01) and a marked increase in Streptococcaceae, Staphylococcaceae, and Enterobacteriaceae (p <0.05 for each) in GnRHa-treated women with endometriosis. This microbial shift was associated with sub-clinical infection in the uterine cavity and cystic fluid of ovarian endometrioma. Furthermore, the 16S metagenome assay detected higher proportions of Streptococcaceae and Staphylococcaceae in ovarian endometrioma cyst fluid compared to non-endometrioma cysts, suggesting a unique microbial signature linked to inflammatory pathogenesis. Interestingly, traditional bacterial culture methods failed to detect colonies in the cystic fluids, while PCR analysis revealed substantial colonization. This discrepancy indicates that sub-clinical infections in the uterine and ovarian microenvironments may contribute to the chronic inflammatory state characteristic of endometriosis. The study also proposed that GnRHa-induced hypoestrogenism might reduce the expression of antimicrobial peptides in the genitourinary tract, facilitating microbial colonization and chronic inflammation.

What Are the Greatest Implications of This Study?

The findings provide robust evidence that intrauterine microbial colonization—particularly of Streptococcaceae, Staphylococcaceae, and Enterobacteriaceae—is prevalent in women with endometriosis and is significantly heightened with GnRHa treatment. This suggests that silent intrauterine infections could exacerbate inflammatory responses and potentially influence disease progression. Furthermore, the detection of bacterial DNA in ovarian endometrioma cystic fluid indicates that microbial colonization extends beyond the uterine environment, potentially affecting ovarian tissue integrity. These insights propose that targeted antimicrobial therapy might mitigate intrauterine bacterial load, reduce inflammation, and improve disease management. The study challenges the traditional view of the sterile uterine environment, suggesting that the bacterial contamination hypothesis should be revisited as a contributing factor in endometriosis pathogenesis.