Hyperbaric Oxygen Therapy (HBOT) as a Promising Candidate in Endometriosis treatment
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Karen Pendergrass
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Karen Pendergrass
Karen Pendergrass is a microbiome researcher specializing in microbiome-targeted interventions (MBTIs). She systematically analyzes scientific literature to identify microbial patterns, develop hypotheses, and validate interventions. As the founder of the Microbiome Signatures Database, she bridges microbiome research with clinical practice. In 2012, based on her own investigative research, she became the first documented case of FMT for Celiac Disease—four years before the first published case study.
BOT demonstrates complete remission and holds significant promise as a candidate for microbiome-targeted intervention for endometriosis.
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Karen Pendergrass
Researched by:
-
Karen Pendergrass
ID
Karen Pendergrass
Microbiome Signatures identifies and validates condition-specific microbiome shifts and interventions to accelerate clinical translation. Our multidisciplinary team supports clinicians, researchers, and innovators in turning microbiome science into actionable medicine.
Karen Pendergrass
Overview 
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References 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
The effect of hyperbaric oxygen therapy in the inflammatory response in a mouse model of endometriosis: An experimental study
September 7, 2021
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Endometriosis •
Endometriosis
Did you know?
Gut microbiota predict endometriosis better than vaginal microbiota.
This study highlights hyperbaric oxygen therapy's (HBOT) role in reducing inflammation and NFκB expression in a mouse model of endometriosis. The findings suggest HBOT as a promising non-invasive treatment for managing endometriosis-associated inflammation, targeting hypoxia-induced molecular pathways and offering potential microbiome benefits through reduced inflammatory burden.
What Was Studied?
This study investigated the effect of hyperbaric oxygen therapy (HBOT) on the inflammatory response in a mouse model of endometriosis. The authors focused on the potential therapeutic role of HBOT in reducing inflammation and modulating molecular pathways, particularly the nuclear factor kappa beta (NFκB) pathway, which plays a crucial role in the pathophysiology of endometriosis. The research aimed to address hypoxia-induced inflammation in endometriosis by exploring how HBOT, through its oxygen-rich environment, could attenuate the inflammatory cascade.
Who Was Studied?
The study utilized 24 healthy adult female Swiss albino mice. The animals were randomly divided into three groups: a pre-test group (Group I), a post-test group receiving HBOT (Group II), and a post-test group without HBOT (Group III). Endometriosis was induced via xenotransplantation of human endometrial cells into the mice's peritoneum. Group II received HBOT for 10 days (30 minutes, three times daily), while Group III did not undergo HBOT but was evaluated at the same time points.
What Were the Most Important Findings?
The study found that HBOT significantly reduced the degree of inflammation in endometriosis-induced mice. Group II (HBOT) showed the lowest inflammation scores (1.60 ± 0.53), compared to the pre-test group (9.41 ± 1.99) and the post-test group without HBOT (2.42 ± 0.53). This reduction in inflammation was associated with a significant decrease in NFκB expression, a key pro-inflammatory transcription factor, in the HBOT group. NFκB expression levels correlated strongly with the degree of inflammation (r = 0.670, p ≤ 0.001). These findings suggest that HBOT alleviates the hypoxia-induced inflammatory response by modulating NFκB signaling and reducing peritoneal inflammation.
From a microbiome perspective, hypoxia-induced inflammatory conditions, such as those observed in endometriosis, are often associated with microbial dysbiosis. HBOT's role in reducing inflammation and altering the microenvironment may indirectly influence microbial populations in the peritoneal cavity. This warrants further exploration into whether HBOT could restore microbial balance by reducing the inflammatory burden and hypoxia.
What Are the Greatest Implications of This Study?
The study provides strong evidence for HBOT as a potential therapeutic strategy for reducing inflammation in endometriosis. By mitigating the effects of hypoxia and decreasing NFκB activation, HBOT addresses a key molecular mechanism in the pathogenesis of endometriosis. Clinically, these findings support the use of HBOT as a non-invasive, adjunctive therapy to manage endometriosis-related inflammation. Furthermore, this study underscores the importance of targeting the hypoxia-inflammatory axis to improve outcomes for endometriosis patients. However, the findings also highlight the need for additional research to optimize HBOT protocols, including duration and dose, to achieve maximal therapeutic benefits.
Remission of Endometriosis by Hyperbaric Oxygen Treatment in Rats
October 18, 2011
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Hyperbaric Oxygen Therapy (HBOT) •
Hyperbaric Oxygen Therapy (HBOT)
Did you know?
Hyperbaric Oxygen Therapy (HBOT) can significantly enhance the body’s natural ability to heal even the most severe and chronic wounds that have resisted conventional treatments for years. For instance, HBOT has been used to save limbs from amputation in diabetic patients with non-healing foot ulcers, dramatically improving their quality of life and preventing severe disability.
Endometriosis •
Endometriosis
Did you know?
Gut microbiota predict endometriosis better than vaginal microbiota.
This study demonstrates hyperbaric oxygen therapy (HBOT) achieves complete remission of endometriotic lesions in a rat model by reducing hypoxia, inflammation, and TNF-α levels. While HBOT shows potential as a non-invasive therapy for endometriosis, further studies are needed to validate its impact on microbiome modulation.
What Was Studied?
This study, conducted by Aydin et al., investigated the effects of long-term hyperbaric oxygen therapy (HBOT) on experimentally induced endometriosis in a rat model. The primary objective was to assess whether HBOT could lead to remission of endometriotic lesions and alleviate inflammation by modulating peritoneal cytokine levels, particularly tumor necrosis factor-alpha (TNF-α). The study evaluated the volume, histopathological changes, and proliferation markers (Ki-67) of endometriotic implants after six weeks of HBOT.
Who Was Studied?
The study was performed on 40 non-pregnant, female Wistar-Albino rats. After surgical induction of endometriosis using an autotransplantation technique, the rats were divided into two groups: one receiving HBOT (20 rats) and a control group (19 rats) without treatment. HBOT was administered for 2 hours daily at 2.5 atm for six weeks. Both groups underwent multiple laparotomies to evaluate lesion volume, histopathological scores, and cytokine levels before and after treatment.
What Were the Most Important Findings?
The study demonstrated that HBOT resulted in complete remission of endometriotic lesions in a rat model. Significant reductions were observed in lesion volume, histopathological scores, Ki-67 proliferation markers, and TNF-α levels in the peritoneal fluid of the HBOT-treated group compared to controls. Specifically, the mean lesion volume decreased by 29.5% (57.4 ± 12.5 mm³ in the HBOT group vs. 94.6 ± 17.2 mm³ in controls). TNF-α levels were significantly lower in the HBOT group (5.33 ± 1.02 pg/mL vs. 8.16 ± 1.76 pg/mL in controls). Reduced Ki-67 staining indicated diminished cellular proliferation within endometriotic lesions. The findings suggest that HBOT alleviates endometriosis-associated inflammation by suppressing NFκB-mediated pro-inflammatory pathways and reducing TNF-α levels, key drivers of inflammation and angiogenesis in endometriosis.
From a microbiome perspective, while the study did not directly assess microbial changes, the reduction in hypoxia and inflammation could indirectly modulate microbial communities. Hypoxia-driven dysbiosis, favoring facultative anaerobes like E. coli and GBS, is a known contributor to endometriosis pathogenesis. By restoring oxygen levels and dampening inflammation, HBOT may reduce the selective advantage for these pathogens, potentially rebalancing the peritoneal microbiome.
What Are the Greatest Implications of This Study?
The study positions HBOT as a potential non-invasive therapeutic strategy for endometriosis, with demonstrated efficacy in reducing lesion size and inflammation. By targeting hypoxia and pro-inflammatory cytokines, HBOT addresses two critical drivers of endometriosis pathophysiology. This has implications for both clinical management and microbiome research, suggesting that HBOT could indirectly modulate microbial dysbiosis in endometriosis. However, the absence of direct microbial analyses leaves a critical gap in validating HBOT as a microbiome-targeted intervention (MBTI). Further studies incorporating microbiome sequencing and metabolomics are essential to establish a direct link between HBOT and microbiome modulation.
Endometriosis
Endometriosis involves ectopic endometrial tissue causing pain and infertility. Validated and Promising Interventions include Hyperbaric Oxygen Therapy (HBOT), Low Nickel Diet, and Metronidazole therapy.
Microbiome-Targeted Interventions (MBTIs)
Microbiome Targeted Interventions (MBTIs) are cutting-edge treatments that utilize information from Microbiome Signatures to modulate the microbiome, revolutionizing medicine with unparalleled precision and impact.
Hyperbaric Oxygen Therapy (HBOT)
Hyperbaric Oxygen Therapy (HBOT) involves breathing pure oxygen in a pressurized chamber, which increases the amount of oxygen dissolved in the blood and delivered to tissues.
Streptococcus agalactiae (GBS)
Streptococcus agalactiae, also known as Group B Streptococcus (GBS), is a Gram-positive, facultative anaerobe commonly found as a commensal organism in the gastrointestinal and urogenital tracts of humans. While asymptomatic colonization is frequent, GBS is also a major pathogen, particularly in neonates, pregnant women, and immunocompromised individuals.
References
- 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)
- Remission of Endometriosis by Hyperbaric Oxygen Treatment in Rats. . Aydin, Y., Atis, A., Uludag, S. et al. . (Reprod. Sci. 18, 941–947 (2011).)
- Remission of Endometriosis by Hyperbaric Oxygen Treatment in Rats. . Aydin, Y., Atis, A., Uludag, S. et al. . (Reprod. Sci. 18, 941–947 (2011).)
Syahrizal D, Mustika C, Ayu Puspita N, Guritno Suryokusumo M, Hendarto H.
The effect of hyperbaric oxygen therapy in the inflammatory response in a mouse model of endometriosis: An experimental study.Int J Reprod Biomed. June 8, 2022
Read ReviewAydin, Y., Atis, A., Uludag, S. et al.
Remission of Endometriosis by Hyperbaric Oxygen Treatment in Rats.Reprod. Sci. 18, 941–947 (2011).
Read ReviewAydin, Y., Atis, A., Uludag, S. et al.
Remission of Endometriosis by Hyperbaric Oxygen Treatment in Rats.Reprod. Sci. 18, 941–947 (2011).
Read Review