Key takeaways:
- Endometriosis was associated with distinct alterations in both vaginal and gut microbiome composition compared with controls.
- Patients with endometriosis demonstrated hormonal imbalances, including lower estradiol and higher luteinizing hormone levels.
- Vaginal microbial shifts included reduced Lactobacillus dominance and increased abundance of EMS-associated bacteria such as Gardnerella and Streptococcus.
- Gut microbiome remodeling in EMS patients was accompanied by widespread functional gene differences linked to host metabolism.
- Findings support gut and vaginal dysbiosis as potential contributors to systemic inflammation and as emerging biomarkers for endometriosis.
Data published in the International Journal of Women’s Health has highlighted a complex interplay between microbial dysbiosis and disease pathogenesis in endometriosis (EMS) patients.1
There is currently limited data about the pathogenesis of EMS, with the retrograde menstruation theory considered the most likely explanation for the condition’s development. However, more recent trials have indicated influence from genetic, hormonal, immunological, and environmental factors.2
“Emerging evidence suggests that dysbiosis of the vaginal and gut microbiomes may contribute to the pathophysiology of EMS,” wrote investigators.1
Clinical assessment and sample collection
The study was conducted to perform an integrated analysis of both the vaginal and gut microbiome in EMS patients. Participants included 5 women with confirmed EMS and 6 non-EMS controls. Those using antibiotics, with a history of human papillomavirus infection, or with a body mass index over 30 mg/m2 were excluded from the analysis.
Endocrine status was determined in all patients using sex hormone testing, with American Society for Reproductive Medicine criteria used to stage EMS cases. Sterile swabs were used to obtain vaginal discharge samples, while fecal discharge samples were collected by participants using sterile stool collection kits.
The E.Z.N.A. Soil DNA Kit (Omega Bio-Tek, USA) was used to extract genomic DNA from vaginal and fecal samples. Quality control was performed for all raw sequences once sequencing reads were obtained. Additionally, clean reads were assembled to contigs to evaluate the microbial functions.
Hormonal findings
An algorithm obtained the top 4 variables from all microbial and functional multiple variables. This information was used to evaluate the impact of the microbial and functional composition on the models.
There were 22 paired vaginal and fecal samples from 11 participants included in the final analysis. No significant differences in body mass index, age, smoking status, or other baseline characteristics were reported between EMS vs non-EMS patients.
However, lower estradiol and increased luteinizing hormone and follicle were reported in the EMS group vs the non-EMS group. This highlighted a disorder of sex hormones in patients with EMS. While both groups reported Firmicutes as the predominant phylum, the non-EMS group had enriched Actinobacteria, while the EMS group had an increased abundance of Bacteroidota.
Vaginal microbiome composition
There were 5 community state types for the microbial composition of the reproductive tract: CST 1, 2, 3, 4, and 5. Of these, CST 1, 2, 3, and 5 predominantly present with Lactobacillus, which plays an important role in the reproductive tract.
Bacteria associated with EMS included Klebsiella, Gardnerella, Streptococcus, and Staphylococcus. Overall, investigators identified 1165 genes that significantly differed between groups. The main differential genes originated from Bifidobacterium, Lactobacillus, and Gardnerella.
When comparing the gut microbiome of EMS vs non-EMS patients, increased Dialister, a biomarker of cervical cancer, was reported in the former. Relatively little variation was reported in the overall functional genes of the EMS group despite the taxonomic remodeling identified in these patients.
Functional gene differences
Overall, 13,466 under-represented and 14,317 over-represented genes were reported in the EMS group. These were primarily derived from the Bacteroides, Prevotella, Oscillibacter, and other common gut bacteria. According to investigators, this indicates potential effects on host metabolism from the altered function spectrum of intestinal microbes.
These results highlighted alterations in the vaginal and gut microbiome of EMS patients. Investigators concluded gut dysbiosis may contribute to systemic inflammation and changes in estrogen metabolism often observed among individuals with EMS.
“This underscores the potential of gut microbiota as a biomarker for EMS and highlights the critical role of gut health in the disease,” wrote investigators.
References
- Zhao Y, Hu X, Li C, et al. Comprehensive analysis of vaginal and gut microbiome alterations in endometriosis patients. International Journal of Women’s Health. 2025. doi:10.2147/IJWH.S561386
- Bellelis P, Podgaec S, Abrão MS. Environmental factors and endometriosis. Rev Assoc Med Bras. 2011;57(4):456–461. doi:10.1590/S0104- 42302011000400022
