Gut microbiome in patients with early-stage and late-stage endometriosis Original paper

What was studied?

This study examined gut microbiome in early-stage and late-stage endometriosis by comparing fecal microbial composition, diversity, and inferred microbial functions across 75 surgically confirmed patients. Using 16S rRNA sequencing (V3–V4 region), the authors investigated how disease severity and dysmenorrhea symptoms relate to microbial composition. Early-stage and late-stage cases showed distinct clustering patterns in principal coordinate analysis, highlighting structural community differences. Late-stage disease also demonstrated notable enrichment of Bartonella, Snodgrassella, Gilliamella, and other taxa, while early-stage cases exhibited higher abundances of Bacteroides, Prevotella, Succiniclasticum, and Rikenellaceae. Functional predictions indicated suppression of steroid biosynthesis pathways in late-stage gut communities, potentially linking hormonal signaling and microbial metabolism. The study further explored dysmenorrhea-associated patterns and found that late-stage patients with dysmenorrhea represented a unique microbial subgroup with distinct beta-diversity signatures.

Who was studied?

Seventy-five adult women (median age 32) residing in Guangzhou, China, were included after surgical confirmation of endometriosis and strict exclusion of confounders such as antibiotic use, pelvic infections, immune disorders, or recent hormonal therapies. Thirty-nine individuals had early-stage disease (ASRM I–II) and thirty-six had late-stage disease (ASRM III–IV). As shown in the study, the two groups did not differ significantly in BMI, marital status, gravidity, or parity, ensuring demographic comparability. Fecal samples were collected one day before surgery under standardized sterile procedures to minimize environmental and dietary variability—an important design strength in microbiome research. Dysmenorrhea was reported by 33 participants and was evenly distributed between early and late stages. This allowed the authors to generate four subgroups (Early_F, Early_T, Late_F, Late_T) that enabled refined stratification of microbial patterns linked specifically to pain phenotypes.

Most important findings

The gut microbiome in early-stage versus late-stage disease showed marked compositional and functional divergence. Structural separation appeared along PCoA2, with late-stage cases displaying higher abundance of Bartonella, Snodgrassella, Bombella, and Commensalibacter species also positively correlated with r-AFS severity scores and CA125 levels. Early-stage disease was enriched in Bacteroides, Prevotella ruminicola, Bacteroides caecimuris, and Succiniclasticum, taxa negatively associated with disease severity. Dysmenorrhea modified the microbial signature, showing that only late-stage dysmenorrhea patients displayed distinct beta-diversity shifts, forming a unique microbial cluster. Functional prediction revealed consistent suppression of steroid biosynthesis pathways in late-stage disease. Two enzymes (EC:2.1.1.41, EC:1.1.1.21) and three orthologs (K00559, K00011, K12688) distinguished early-stage from late-stage, linking microbial metabolism to hormonal signaling. The repeated enrichment of Gilliamella, Bartonella, Snodgrassella, and related taxa suggests microbiome-based severity signatures relevant for clinical classifiers.

Key implications

This study strengthens evidence that endometriosis progression is accompanied by specific microbial shifts, particularly reduction of Bacteroides–Prevotella groups and increased colonization by taxa associated with immune tolerance. The suppressed steroid biosynthesis pathways in late-stage disease suggest that gut microbes may participate in hormonal modulation central to endometriosis pathophysiology. The distinct microbial phenotype observed in late-stage dysmenorrhea cases indicates a possible microbiome-influenced pain subtype. These findings provide candidate microbial signatures for diagnostic modeling and suggest that targeted microbiome modulation—potentially via probiotics affecting steroid metabolism—may serve as adjunctive care.

Citation

Cai Z, Zhou Z, Huang S, Ma S, Chen Y, Cao Y, Ma Y. Gut microbiome in patients with early-stage and late-stage endometriosis. BMC Women’s Health. 2025;25:163. doi:10.1186/s12905-025-03689-0