Antibiotic therapy with metronidazole reduces endometriosis disease progression in mice: a potential role for gut microbiota Original paper

What Was Studied?

This study examined the impact of antibiotic therapy with metronidazole on endometriosis disease progression in a mouse model, exploring its potential effects on gut microbiota and inflammation. Researchers induced endometriosis in mice through surgical transplantation of uterine tissue onto the peritoneal wall. Mice were then treated with either broad-spectrum antibiotics (vancomycin, neomycin, metronidazole, and ampicillin) or metronidazole alone, with control groups receiving vehicle-only treatment. The primary goal was to determine if modulating gut bacteria through antibiotic therapy could reduce endometriotic lesion growth and inflammation, potentially revealing gut microbiota as a therapeutic target.

Who Was Studied?

The study utilized a well-established mouse model of surgically induced endometriosis, where uterine tissue from estrus-stage mice was autologously transplanted onto the peritoneal wall. Mice were separated into groups receiving either broad-spectrum antibiotics, metronidazole alone, or vehicle treatments. To assess the effect of gut microbiota on disease progression, fecal transplantation experiments were performed, where feces from endometriosis-induced mice were gavaged into metronidazole-treated mice to observe the restoration of lesion growth and inflammation.

What Were the Most Important Findings?

The findings demonstrated that antibiotic therapy, particularly with metronidazole, significantly reduced the size and volume of endometriotic lesions in mice. Mice treated with broad-spectrum antibiotics showed a five-fold reduction in lesion size and markedly fewer proliferating cells and macrophages within the lesions compared to vehicle-treated controls (p <0.01). Metronidazole-treated mice specifically exhibited smaller ectopic lesions than those receiving neomycin or vehicle, suggesting a unique sensitivity of certain gut bacteria to metronidazole’s antimicrobial activity. Importantly, inflammation markers, including IL-1β, TNF-α, IL-6, and TGF-β1, were significantly reduced in the peritoneal fluid of metronidazole-treated mice, indicating a diminished inflammatory response.

Additionally, fecal transplantation experiments highlighted the role of gut microbiota in lesion progression. Oral gavage of feces from endometriosis-induced mice restored lesion growth and inflammation in metronidazole-treated mice, implicating gut bacteria as contributors to disease persistence. 16S rRNA sequencing of fecal samples showed that Bacteroidetes were enriched in endometriosis-induced mice and nearly absent in metronidazole-treated mice, suggesting that the suppression of specific microbial populations might underlie the observed therapeutic effects. This reduction in Bacteroidetes correlated with decreased inflammatory responses and smaller lesion sizes, underscoring the interplay between gut microbiota and endometriosis pathology.

What Are the Greatest Implications of This Study

The study provides compelling evidence that targeting the gut microbiota with antibiotics like metronidazole can effectively reduce endometriotic lesion growth and inflammation in a mouse model. The findings suggest that Bacteroidetes may contribute to lesion persistence and immune activation, and their depletion through metronidazole treatment alleviates these pathological effects. This raises the possibility of microbiota-targeted therapies as a novel approach to managing endometriosis, potentially offering a non-hormonal alternative to traditional treatments. Furthermore, the study highlights the significance of gut microbiota modulation in controlling systemic and local inflammatory responses, paving the way for research into gut-mediated mechanisms of endometriosis and microbiome-based therapeutic strategies.