Validation of Metronidazole as a microbiome-targeted intervention for Endometriosis

Overview

Metronidazole demonstrates significant potential as a microbiome-targeted intervention (MBTI) for endometriosis by reducing key pathogenic taxa, modulating inflammation, and supporting microbial balance. Studies reveal that metronidazole reduces ectopic lesion size and inflammation in mice, while restoring lesion growth through fecal gavage highlights the microbiome’s role in lesion progression. ^[1] By targeting microbial MMAs such as Bacteroides, Fusobacterium nucleatum, Bacteroides fragilis, and Escherichia coli, metronidazole aligns with the pathological and microbial hallmarks of endometriosis.

Microbial Modulation

Metronidazole is particularly effective against Bacteroides and Fusobacterium nucleatum, two microbial taxa consistently elevated in endometriosis. ^[2] Importantly, it also reduces the growth rate of Escherichia coli when in the presence of Bacteroides fragilis, demonstrating its selective activity in complex microbial ecosystems. ^[3] Notably, metronidazole has also been shown to increase lactobacilli populations at specific concentrations (128–256 mg/ml), contributing to the restoration of beneficial microbiota and reducing dysbiosis-associated inflammation​. ^[4] These microbial shifts align with the known endometriosis microbiome signature and highlight metronidazole’s dual ability to suppress dysbiotic taxa and support beneficial microbes.

Validation of the Microbiome Signature

The endometriosis microbiome signature features elevated levels of Bacteroides and Fusobacterium nucleatum, which contribute to lesion progression and inflammation. Metronidazole’s ability to specifically reduce these taxa, coupled with its capacity to increase lactobacilli under appropriate conditions, reinforces the clinical relevance of this microbiome signature. The correlation between metronidazole’s microbial effects and reduced lesion size further validates the signature as a reflection of endometriosis pathogenesis.

Dual Validation of MBTI and Microbiome Signature

Metronidazole exemplifies the interconnectedness of microbial dysbiosis and systemic pathology in endometriosis. By reducing key MMAs while promoting lactobacilli growth, metronidazole serves as both an effective MBTI and a tool for validating the microbiome signature of the condition. The observed clinical outcomes, including reduced lesion growth and inflammation, confirm the utility of metronidazole in addressing the microbial and pathological drivers of endometriosis.

Conclusion

Metronidazole offers a multifaceted approach to endometriosis by targeting microbial imbalances and modulating inflammation. Its ability to reduce key dysbiotic taxa, increase lactobacilli at specific doses, and suppress lesion progression validates its role as an MBTI and strengthens the clinical relevance of the endometriosis microbiome signature. These findings position metronidazole as a promising therapeutic option in the management of endometriosis.

References

1. Antibiotic therapy with metronidazole reduces endometriosis disease progression in mice: a potential role for gut microbiota. . Chadchan SB, Cheng M, Parnell LA, et al.. (Hum Reprod. 2019)
2. Analysis of Fusobacterium persistence and antibiotic response in colorectal cancer.. Bullman S, Pedamallu CS, Sicinska E, Clancy TE, Zhang X, Cai D, Neuberg D, Huang K, Guevara F, Nelson T, Chipashvili O, Hagan T, Walker M, Ramachandran A, Diosdado B, Serna G, Mulet N, Landolfi S, Ramon Y Cajal S, Fasani R, Aguirre AJ, Ng K, Élez E, Ogino S, Tabernero J, Fuchs CS, Hahn WC, Nuciforo P, Meyerson M.. (Science. 2017)
3. Activity of metronidazole against Escherichia coli in experimental intra-abdominal sepsis.. Onderdonk AB, Louie TJ, Tally FP, Bartlett JG.. (J Antimicrob Chemother. 1979)
4. Effect of metronidazole on the growth of vaginal lactobacilli in vitro.. Simoes JA, Aroutcheva AA, Shott S, Faro S.. (Infect Dis Obstet Gynecol. 2001)