Correlation of fecal metabolomics and gut microbiota in mice with endometriosis Original paper

What Was Studied?

This study investigated the correlation between fecal metabolomics and gut microbiota in mice with endometriosis. Using a controlled experimental design, researchers constructed an endometriosis (EMS) mouse model with female C57BL/6J mice and analyzed fecal samples through non-targeted metabolomics and 16S rRNA sequencing. The primary objective was to identify differential metabolites and microbial compositions that could serve as biomarkers for endometriosis and provide insight into the metabolic pathways affected by gut dysbiosis in EMS. Functional prediction of the gut microbiota was performed using PICRUSt, and metabolite-microbiota correlations were assessed through Spearman correlation coefficients.

Who Was Studied

The study involved female C57BL/6J mice, which were divided into two groups: an EMS group and a control group. Endometriosis was induced in the EMS group through intraperitoneal injection of endometrial fragments, while the control group received saline injections with adipose tissue. Fecal samples were collected from both groups, processed for liquid chromatography-mass spectrometry (LC-MS), and subjected to 16S rRNA sequencing to map microbial diversity and metabolic profiles. The study aimed to simulate the inflammatory and microbiome-related characteristics of endometriosis in humans by using this established animal model.

What Were the Most Important Findings?

The study identified significant shifts in both fecal metabolomics and gut microbiota composition in mice with endometriosis compared to controls. A total of 156 named differential metabolites were screened, with key changes observed in pathways linked to secondary bile acid biosynthesis and alpha-linolenic acid (ALA) metabolism. Notably, there was an increased abundance of chenodeoxycholic acid (CDCA) and ursodeoxycholic acid (UDCA) alongside a decreased presence of ALA and 12,13-EOTrE in the EMS mice. Microbial diversity was reduced in the EMS group, with a specific loss in Bacteroides and Firmicutes, contrasted by increases in Proteobacteria and Verrucomicrobia. At the genus level, there was a marked increase in Allobaculum, Akkermansia, Parasutterella, and Rikenella, with significant decreases in Lachnospiraceae, Lactobacillus, and Bacteroides. Functional predictions revealed alterations in oxidative phosphorylation, alanine, aspartate, glutamate metabolism, and starch and sucrose metabolism. Importantly, the study identified Sphingobium and Pseudomonas viridiflava as consistently enriched in EMS mice, suggesting their potential role in inflammation and metabolic disruption. The correlation analysis demonstrated strong associations between specific metabolites (like CDCA and ALA) and microbial shifts, indicating a complex interaction between gut dysbiosis and metabolic imbalances in endometriosis.

What Are the Greatest Implications of This Study?

The findings suggest that endometriosis is associated with profound shifts in gut microbiota and fecal metabolomics, which may contribute to chronic inflammation and disease persistence. The increased levels of chenodeoxycholic acid (CDCA) and ursodeoxycholic acid (UDCA), combined with reductions in ALA, indicate that bile acid metabolism and fatty acid dysregulation are central to the pathogenesis of endometriosis. The enrichment of Allobaculum, Akkermansia, Parasutterella, and Rikenella in the gut microbiota suggests these species could be contributing to local and systemic inflammation, disrupting gut barrier integrity. These microbial and metabolomic signatures could serve as non-invasive biomarkers for diagnosing endometriosis and may offer new therapeutic targets focused on restoring microbial balance and metabolic homeostasis. Furthermore, the study highlights the critical role of gut microbiota in modulating immune responses and metabolic pathways, paving the way for microbiome-targeted treatments in endometriosis management.