Overview

Endometriosis is a chronic inflammatory condition characterized by the ectopic growth of endometrial tissue, often accompanied by microbial dysbiosis and a hypoxic, pro-inflammatory peritoneal environment. Microbiome-targeted interventions (MBTIs) aim to modulate microbial communities to restore homeostasis and improve disease outcomes. While hyperbaric oxygen therapy (HBOT) has shown significant promise in addressing endometriosis-associated inflammation and hypoxia, it has yet to meet all criteria for validation as an MBTI. This article explores the potential of HBOT as a Promising Candidate (PC), highlights its current limitations, and proposes immediate steps to bridge these gaps to become a validated MBTI.

Why HBOT Holds Potential for Endometriosis

Reduction of Hypoxia and Its Microbial Implications

Hypoxia is a hallmark of endometriosis lesions, contributing to inflammation and supporting facultative anaerobes such as Escherichia coli (E. coli) and Group B Streptococcus (GBS). These microbes thrive in low-oxygen environments, where they exacerbate inflammation by producing virulence factors like lipopolysaccharides and promoting immune dysregulation. HBOT directly addresses hypoxia by delivering 100% oxygen at elevated atmospheric pressure, improving tissue oxygenation and creating an environment less favorable for these pathogens. While direct microbial data are lacking, the reduction in hypoxia suggests an indirect modulatory effect on the microbial community.

Anti-inflammatory Effects on NFκB and TNF-α Pathways

Inflammation is central to the pathophysiology of endometriosis and is strongly associated with microbial dysbiosis. HBOT has been shown to significantly reduce pro-inflammatory mediators, such as tumor necrosis factor-α (TNF-α) and nuclear factor kappa B (NFκB) activity, as evidenced by both the Syahrizal et al. and Aydin et al. studies. ^[1]2. By decreasing these inflammatory drivers, HBOT not only alleviates the inflammatory state but also potentially disrupts the favorable conditions for facultative anaerobes, which thrive in inflamed environments.

Resolution of Endometriotic Lesions

The Aydin study demonstrated complete remission of endometriosis lesions after 6 weeks of HBOT (2 hours daily at 2.5 atm) in a rat model. ³ This finding underscores HBOT’s potential as a therapeutic intervention for endometriosis. While the exact microbial dynamics were not analyzed, the remission of lesions suggests a potential restoration of microbial and immunological balance in the peritoneal cavity.

Microbial Dysbiosis and Immune Modulation

Endometriosis is associated with microbial dysbiosis, including increased E. coli and decreased protective Lactobacillus species. HBOT’s immunomodulatory effects—such as suppressing macrophage-driven cytokine production—may recalibrate immune responses, indirectly influencing microbial communities. Additionally, HBOT’s ability to act as a bacteriostatic or bactericidal agent against anaerobic and facultative anaerobic bacteria suggests it could mitigate pathogen-driven dysbiosis.

Current Limitations in Validating HBOT as an MBTI

To validate an MBTI, the intervention must demonstrate the ability to modulate the microbiome by decreasing disease-associated taxa or increasing health-associated taxa while also improving clinical outcomes for the condition in question. Although hyperbaric oxygen therapy has shown clinical efficacy in reducing inflammation and resolving lesions, its direct impact on microbial communities remains unstudied in endometriosis models. Without microbiome sequencing or other microbial analyses conducted before and after HBOT, it is not possible to confirm whether HBOT directly modulates the endometriosis-associated microbiome signature.

Immediate Actions for Validation

To validate microbiome-targeted interventions for HBOT-treated endometriosis, immediate actions should include both animal and clinical studies. Animal studies can utilize 16S rRNA sequencing or metagenomics to analyze peritoneal microbiome changes in endometriosis-induced models before and after HBOT, focusing on shifts in disease-associated taxa (e.g., E. coli, GBS) and health-associated taxa (e.g., Lactobacillus). Clinical studies should involve collecting peritoneal fluid or stool samples from endometriosis patients undergoing HBOT to assess microbial shifts.

HBOT as a Promising Candidate

Despite the lack of direct evidence linking HBOT to microbial changes in endometriosis, its profound effects on inflammation, hypoxia, and lesion resolution and remission suggest it has significant potential as an MBTI. By targeting the hypoxia-inflammatory axis, HBOT indirectly addresses key drivers of dysbiosis, making it a strong candidate for further research. Until microbiome-specific data are available, HBOT should be regarded as a “Promising Candidate” for endometriosis. This classification encourages continued investigation while acknowledging the need for direct microbiome analyses. With additional research, HBOT could be fully validated as an MBTI, providing a non-invasive, multifaceted approach to managing endometriosis and its associated dysbiosis.

Conclusion

Hyperbaric oxygen therapy has shown great promise in addressing the inflammatory and hypoxic components of endometriosis. While it has yet to meet all criteria for MBTI validation, its potential to indirectly modulate the microbiome through its systemic effects positions it as a promising candidate. Future studies should prioritize integrating microbiome data into HBOT research to elucidate its role as an MBTI for endometriosis fully.

Research Feed

References

1. The effect of hyperbaric oxygen therapy in the inflammatory response in a mouse model of endometriosis: An experimental study.. Syahrizal D, Mustika C, Ayu Puspita N, Guritno Suryokusumo M, Hendarto H.. (Int J Reprod Biomed. June 8, 2022)
2. Remission of Endometriosis by Hyperbaric Oxygen Treatment in Rats. . Aydin, Y., Atis, A., Uludag, S. et al. . (Reprod. Sci. 18, 941–947 (2011).)
3. Remission of Endometriosis by Hyperbaric Oxygen Treatment in Rats. . Aydin, Y., Atis, A., Uludag, S. et al. . (Reprod. Sci. 18, 941–947 (2011).)