The inconsistent pathogenesis of endometriosis and adenomyosis: insights from endometrial metabolome and microbiome.
Journal:
mSystems
Published Date:
Apr 22, 2025
Abstract
UNLABELLED: Endometriosis (EM) and adenomyosis (AM) are interrelated gynecological disorders characterized by the aberrant presence of endometrial tissue and are frequently linked with chronic pelvic pain and infertility, yet their pathogenetic mechanisms remain largely unclear. In this cross-sectional study, we analyzed endometrial samples from 244 participants, split into 91 EM patients, 56 AM patients, and 97 healthy controls (HC). We conducted untargeted liquid chromatography-mass spectrometry (LC-MS) and 5R 16S rRNA sequencing to examine endometrial metabolome and microbiome profiles. Additionally, we integrated transcriptomic analysis using nine transcriptomic data sets to investigate the biological basis of these conditions. Metabolomic profiling and 16S rRNA sequencing revealed distinct metabolic and microbial signatures. Specific pathways, including linoleic acid and glycerophospholipid metabolism, show significant alterations in both conditions. Notably, four metabolites, including phosphatidylcholine 40:8 [PC(40:8)], exhibited marked changes in both EM and AM, suggesting shared pathological features. Furthermore, taxonomic analysis identified unique bacterial species associated with each condition, particularly those belonging to the phylum Proteobacteria, which correlated with altered metabolic signatures. Machine learning models demonstrated high predictive accuracy for differentiating between AM, EM, and HC based on metabolic and microbial signatures. Integrative analysis with transcriptomic data highlighted distinct pathways related to immune response and signaling transduction for each condition. Our study provides fresh insights into the pathogenesis of AM and EM through a multi-omic approach, suggesting potential inconsistencies in the underlying pathogenetic mechanisms.
