Oral, Vaginal, and Stool Microbial Signatures in Patients With Endometriosis as Potential Diagnostic Non-Invasive Biomarkers: A Prospective Cohort Study Original paper

What was studied?

This prospective cohort pilot study examined the oral, vaginal, and stool microbiota of three cohorts: confirmed endometriosis patients (ENDO, n=21), patients with other gynecological conditions but no endometriosis (N-ENDO, n=24), and healthy controls without gynecologic disease (HC, n=19). Using 16S rRNA sequencing, the study sought to identify non-invasive microbial biomarkers that could potentially differentiate individuals with endometriosis from others, with the ultimate goal of developing a diagnostic tool.

Who was studied?

A total of 64 women were studied, all age- and sex-matched. ENDO and N-ENDO participants were recruited from a hospital setting where they underwent laparoscopy with histological confirmation. Healthy controls were recruited from a separate longitudinal study (MothersBabies), with no known gynecological pathology.

Key Findings:

The study revealed significant microbial diversity and compositional differences in oral and stool samples among patients with endometriosis, non-endometriosis gynecologic conditions, and healthy controls, while vaginal samples showed no significant variation. Specifically, alpha diversity was reduced in the stool microbiota of endometriosis patients compared to healthy controls, and beta diversity analysis confirmed that both oral and stool communities were distinctly structured across cohorts. LEfSe analysis identified differentially abundant taxa specific to body site and disease severity. In stool samples, Phascolarctobacterium and Lactobacillus were enriched in endometriosis, with Actinomyces elevated in minimal/mild cases and Paraprevotellaceae in moderate/severe cases.

Oral samples from patients with moderate/severe endometriosis were characterized by a marked increase in Fusobacterium, a genus previously shown to facilitate lesion development in murine models and implicated in human periodontal disease. This is especially relevant given the higher incidence of periodontitis in endometriosis patients. Cardiobacterium was elevated in mild disease. In vaginal samples, the enrichment of Escherichia, Enterococcus, and Tepidimonas supports the bacterial contamination hypothesis, which posits that lipopolysaccharide (LPS)-mediated inflammation may play a role in lesion formation.

Here is a summary of the differentially abundant taxa by body site and disease severity:

Implications for Microbiome Research and Clinical Practice:

The study underscores the potential for developing a non-invasive diagnostic tool for endometriosis using microbial biomarkers obtained from oral or stool samples. Specific taxa such as Fusobacterium, Escherichia, and Phascolarctobacterium emerged as promising microbial targets for future mechanistic and therapeutic investigations due to their known roles in modulating inflammation and estrogen metabolism. Additionally, the observed enrichment of Lactobacillus in the stool of patients with endometriosis suggests a possible link to estrobolome activity, with implications for enhanced estrogen recycling and disease progression. Furthermore, the detection of overlapping genera in the gut and peritoneal fluid, as reported in other studies, lends support to the hypothesis that intestinal bacterial translocation may contribute to the peritoneal inflammation characteristic of endometriosis.