Inflammatory Bowel Disease

Written By Elizabeth Gaffney

The Potential of Hyperbaric Oxygen Therapy (HBOT) in treating Inflammatory Bowel Disease (IBD)

Introduction

Hyperbaric Oxygen Therapy (HBOT) consists of breathing oxygen at a pressure higher than local atmospheric pressure for multiple sessions for the treatment or prevention of specific diseases. As per the European Code of Good Practice (Kot et al.), there is a general consensus that the term HBOT can only be applied when the partial pressure of oxygen in breathing mixture exceeds 1.5 absolute atmosphere (ATA) for a minimum period of 60 minutes (excluding compression and decompression).

HBOT has a potential role in the treatment of inflammatory bowel diseases (IBDs), such as Crohn’s disease and ulcerative colitis. HBOT enhances oxygen delivery to the affected tissues, reduces inflammation, promotes gut healing, and improves tissue oxygenation, potentially easing IBS symptoms.

Mechanisms of Action

During HBOT, patients breathe a gas mixture with a higher concentration of oxygen in a chamber in which the pressure is higher than atmospheric pressure (2 ATA) for > 60 minutes for multiple sessions. HBOT may benefit patients with IBD through several mechanisms, primarily by enhancing oxygen delivery to tissues to relieve chronic hypoxia and promote healing (Cannellotto et al., 2024).

1. Enhanced Oxygenation: Due to inflammation and disruption of the vasculature, the IBD intestinal tissue is often hypoxic (Cummins & Crean, 2017), which prevents healing. HBOT increases the dissolved oxygen in plasma, significantly enhancing diffusion to tissues, thus alleviating hypoxia and stimulating tissue repair pathways (Alenazi et al., 2021; McCurdy et al., 2022).

2. Angiogenesis: Although angiogenesis is part of the pathological process of IBD, angiogenesis is essential during healing of ulcers (Tarnawski et al., 2014). HBOT stimulates angiogenesis by inducing the release of VEGF and other pro-angiogenic factors (Huang et al., 2020) and may improve blood supply to the intestines.

3. Anti-Inflammatory Effects: Chronic inflammation is a hallmark of IBD. HBOT exerts anti-inflammatory effects by decreasing the levels of pro-inflammatory cytokines (Capó et al., 2023), such as TNFa, IL-1 and IL-6, which are important in IBD (Weisz et al., 1997). HBOT also ameliorates intestinal and systematic inflammation by modulating dysbiosis of the gut microbiota in Crohn’s disease (Li et al, 2024).

4. Stem Cells: As well as modulating angiogenesis and the endothelium by mobilising endothelial progenitor cells (Lin et al., 2018), HBOT may promote mucosal healing by raising stem cells in the injured areas (Bekheit et al., 2016).

5. Reduction of Oedema: IBD may involve oedema and HBOT may reduce oedema and swelling in experimental models of colitis (Rossignol, 2012).

Benefits of HBOT for Patients with IBD

HBOT is generally well tolerated and serious side effects are rare (Camporesi, 2014; Zhang et al., 2023). Patients with IBD may experience a range of benefits from adjunctive HBOT, including its potential to reduce inflammation, alleviate symptoms, and promote tissue healing, which can ultimately enhance quality of life.

1. Symptom Relief: Many IBD patients experience frequent relapses and may develop complications such as strictures, fistulas, and abscesses that severely impact quality of life. HBOT’s ability to reduce inflammation and promote healing can provide significant symptom relief (McCurdy et al., 2022).

2. Reduced Dependence on Medications: Standard treatments for IBD often include corticosteroids and immunosuppressants, which can have significant long-term side effects, such as osteoporosis, increased infection risk, and liver toxicity (Yasir et al., 2023; Stallmach et al., 2010) By increasing rates of clinical remission in IBD (McCurdy et al., 2022), HBOT may reduce dependence on these drugs and reduce the adverse effects associated with prolonged use.

3. Reduced Healing Times: Symptoms and complications like fistulas and abscesses can be slow to heal after treatment or surgery, especially in patients with compromised immune systems. HBOT may accelerate healing by enhancing tissue repair (Bekheit et al., 2016; Feitosa et al., 2016) leading to shorter recovery times.

4. Enhanced Response in Refractory Cases: A subset of IBD patients does not respond to conventional therapies, leading to chronic symptoms and complications. HBOT may help this refractory population (Feitosa et al., 2016; Feitosa et al., 2021), offering an option for patients who may otherwise have limited treatment avenues.

Clinical Evidence Supporting HBOT of IBD

While research on HBOT in IBD is still emerging, a growing body of clinical evidence, including case reports and small-scale studies, suggests that HBOT can be an effective adjunctive therapy, particularly for patients with complicated or refractory disease.

1. Reviews and Meta-analyses: There have been numerous reviews and meta-analyses of the efficacy of HBOT for IBD. Examples include Dulai et al. (2014), Wu et al. (2021), Chen et al. (2021), Singh et al. (2021), You et al. (2022), McCurdy et al. (2022), Kuar et al. (2023), but there are many others. The meta-analysis of McCurdy et al. (2022) included 19 studies comprising 809 patients. Although the HBOT protocols varied significantly, the majority were typically performed at 2–2.4 ATA for 90 minutes and included 20–40 sessions. The authors concluded that HBOT is safe and associated with substantial rates of clinical remission for multiple IBD phenotypes

2. HBOT in Ulcerative Colitis: Several systematic reviews and meta-analyses have concluded that HBOT may be an effective adjunctive treatment for ulcerative colitis (Chen et al., 2021; Luo et al., 2021; Singh et al., 2021). The effectiveness of HBOT in treating IBD has been explored with a particular focus on moderate to severe ulcerative colitis patents who did not respond to standard treatments (McCurdy et al., 2022). In an RCT, patients treated with HBOT had a higher rate of clinical remission and a lower incidence of needing second-line therapy (Dulai et al., 2018). In a phase 2B randomised trial, 20 patients underwent HBOT and 55% showed improvement, including significant reductions in stool frequency, rectal bleeding, and C‐reactive protein levels, without any severe side effects, and responders had lower rates of re-hospitalisation or colectomy within 3 months compared to non-responders (Dulai et al., 2020). In another study, patients with severe ulcerative colitis received 10 sessions of HBOT alongside 400 mg hydrocortisone and IV fluids over two weeks and showed significant reductions in inflammatory markers and disease scores compared to those who received only hydrocortisone and fluids (Abdel-Hakim et al., 2021).

3. HBOT in Crohn’s disease: A number of systematic reviews and meta-analyses have concluded that HBOT may be an effective adjunctive treatment for Crohn’s disease (Dulai et al., 2014; Singh et al, 2021; McCurdy et al., 2022; Dokmak et al., 2024). In a clinical trial involving Crohn’s disease patients with perianal involvement who were unresponsive to conventional treatments, HBOT (100% O2, 2.4 ATA, 90 minutes, 20–60 sessions) led to complete healing of perianal lesions in eight out of ten patients, with three responding after just one course (Lavy et al., 1994). In another study in Amsterdam, patients with refractory Crohn’s disease underwent HBOT (100% O2, 2.4 ATA, 120 mins, 10–86 sessions), which led to clinical and radiologic improvements of perianal fistula at week 16 and at one‐year follow‐up (Lansdorp et al., 2022).

 Conclusion

HBOT is a promising adjunctive treatment for several types of IBD, including ulcerative colitis and Crohn’s disease. Clinical evidence, including randomised controlled trials and meta-analysis, support the benefits of HBOT in increasing rates of remission in IBD patients and promoting healing. HBOT, therefore, may be a safe and effective tool in the management of IBD.

References

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Elizabeth Gaffney https://www.sourceprojects.co
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