The role of the vaginal microbiome in distinguishing female chronic pelvic pain caused by endometriosis/adenomyosis Original paper

What was studied?

This study investigated whether the composition of the vaginal microbiome could serve as a diagnostic biomarker to differentiate chronic pelvic pain (CPP) caused by endometriosis or adenomyosis (EM/AM) from other causes of chronic pelvic pain syndrome (CPPS) in women. Using 16S rRNA sequencing (V4 region), the researchers profiled the vaginal microbiota of 37 women with EM/AM-associated CPP, 25 with CPPS from other causes, and 66 healthy controls without CPPS. Additionally, the study explored whether combining vaginal microbial markers with serum CA125 could improve differential diagnostic accuracy.

Who was studied?

The study included 128 premenopausal women attending the gynecology department of Peking Union Medical College Hospital. These were stratified into three groups: 37 women with surgically confirmed EM/AM-associated CPP, 25 women with non-EM/AM CPPS (adhesions, hydrosalpinx, infertility), and 66 women without any chronic pelvic pain. All participants were HPV-negative, had not recently used antibiotics or vaginal products, and were matched for age, gravidity, parity, and contraceptive method to control for confounding variables.

What were the most important findings?

The vaginal microbiome of women with EM/AM-associated CPP exhibited significantly higher alpha diversity than those in the CPPS and healthy control groups. Taxonomic analyses revealed distinct microbial signatures: increased abundance of Clostridium butyricum, Clostridium disporicum, Alloscardovia omnicolens, and Veillonella montpellierensis, alongside a marked depletion of Lactobacillus jensenii, Lactobacillus reuteri, and Lactobacillus iners. These differentially abundant taxa serve as potential microbiome biomarkers.

Diagnostic performance analysis demonstrated that a combination of microbial biomarkers (specifically, a relative abundance of Clostridium disporicum >0.001105% and Lactobacillus reuteri<0.1911349%) yielded 81.08% sensitivity and 52% specificity for identifying EM/AM-associated CPP. When combined with serum CA125 levels, sensitivity increased to 89.19%, although specificity remained unchanged. Functional predictions via PICRUSt revealed enrichment of metabolic pathways such as amino acid metabolism, energy metabolism, and metabolism of cofactors and vitamins in EM/AM patients, along with downregulation of membrane transport and nucleotide metabolism compared to controls. These shifts may reflect microbial contributions to inflammation and pain signaling pathways implicated in EM/AM-associated CPP.

From a microbiome signature standpoint, the enriched taxa—particularly Clostridium disporicum and Alloscardovia omnicolens—emerge as Major Microbial Associations (MMAs) due to their consistent elevation in EM/AM patients. Conversely, Lactobacillus jensenii and L. reuteri, known for their protective, anti-inflammatory properties, are depleted, suggesting their role in maintaining vaginal eubiosis and preventing EM/AM-associated pathogenesis.

What are the greatest implications of this study?

This research provides compelling evidence that the vaginal microbiome harbors discriminative microbial signatures capable of differentiating EM/AM-associated CPP from other forms of chronic pelvic pain. The incorporation of specific microbial biomarkers, particularly when paired with serum CA125, may improve non-invasive diagnostic accuracy, enabling earlier and more targeted therapeutic intervention. Clinically, these findings underscore the potential of microbiome-informed diagnostics for gynecological conditions where conventional markers fall short. More broadly, this study suggests that vaginal dysbiosis, characterized by Lactobacillus depletion and enrichment of saccharolytic and anaerobic species, could be causally linked to EM/AM pathogenesis, possibly via inflammatory or metabolic pathways. Future studies incorporating metagenomic or metabolomic analyses are warranted to functionally validate these microbial associations and to explore the feasibility of microbial modulation as a therapeutic strategy.