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Pain & inflammation

Crohn's disease and ulcerative colitis

Hyperbaric oxygen has been studied in Crohn's disease and ulcerative colitis for over thirty years, mostly in small case series. The strongest evidence comes from two sham-controlled randomised trials in people admitted to hospital with ulcerative colitis flares, which reported higher remission rates and fewer people needing rescue therapy or colectomy, and from a prospective cohort in treatment-refractory perianal Crohn's fistulas showing meaningful clinical and MRI improvement. The biology is coherent, but the trials are small, and larger studies are in progress.

Evidence so far
Moderate
Reading timeAbout 12 minutes

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Why this is being studied

Inflammatory bowel disease leaves the gut wall inflamed, swollen and starved of oxygen, which is one reason it heals so poorly. This path collects the research on whether pressurised oxygen can interrupt that cycle, from sham-controlled trials in hospitalised ulcerative colitis to the Dutch HOT-TOPIC study of perianal Crohn's fistulas. It is written for members and clinicians who want the evidence laid out honestly, including its limits.

Where the evidence stands

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The mechanism

What is going on, and why this might help

What is going on in the body

Crohn's disease and ulcerative colitis are chronic inflammatory diseases of the gut wall driven by an inappropriate immune response to the intestinal microbiome in genetically susceptible people. Ulcerative colitis affects the inner lining of the colon in a continuous pattern; Crohn's can affect any part of the gut, extends through the full thickness of the wall and can form fistulas, particularly around the anus. In both, inflamed tissue is markedly hypoxic: swelling and microvascular damage restrict blood flow while immune cells consume large amounts of oxygen. This hypoxia stabilises HIF-1α, which in the gut has mixed effects, and drives further release of TNF-α, IL-1β and IL-6. The result is a self-sustaining cycle of hypoxia, inflammation and impaired mucosal healing, with fistula tracts lined by chronically inflamed, poorly perfused tissue that will not close.

Where oxygen comes in

Hyperbaric oxygen delivers dissolved oxygen directly into hypoxic bowel wall and fistula tracts, breaking the hypoxia-inflammation loop. In animal models of colitis it reduces TNF-α, IL-1β and IL-6, lowers neutrophil infiltration and oxidative damage, and speeds mucosal repair. In human trials in ulcerative colitis, falls in faecal calprotectin and CRP accompanied clinical improvement, and a 2026 pilot study reported measurable changes in bowel perfusion. For fistulising Crohn's the mechanism overlaps with chronic wound healing: oxygen supports fibroblast collagen synthesis, angiogenesis via VEGF, neutrophil killing of bacteria in the tract, and is directly hostile to the anaerobes that colonise fistulas. Stem-cell mobilisation (Thom 2006) may contribute to mucosal regeneration. Hyperbaric oxygen also appears to shift immune signalling in the gut, with studies showing changes in mucosal T-cell and neutrophil populations.

How solid is this

Supported by trials, though not yet established. Anti-inflammatory and mucosal healing mechanisms are well demonstrated in animal colitis models. In humans, two sham-controlled randomised trials in hospitalised ulcerative colitis (Dulai et al. 2018 and 2020) and a prospective cohort in perianal Crohn's (Lansdorp et al. 2021) support the mechanism, but numbers are small and larger trials are under way. Key references: Dulai et al. 2018; Lansdorp et al. 2021.

Explainer illustration

The studies

Every study is laid out the same way: what the researchers wanted to find out, who took part, what they actually did, what they found, why it might work and where the limits are. No jargon, and a link to the original if you want to read it yourself.

Each study is laid out the same way: what the researchers asked, who took part, what they did, what they found, why it might work, and where the limits are. The clinician layer at the end of each one carries the numbers.

Paper 1

Hyperbaric oxygen therapy is well tolerated and effective for ulcerative colitis patients hospitalized for moderate-severe flares: a phase 2A pilot multi-center, randomized, double-blind, sham-controlled trial

Dulai et al. · American Journal of Gastroenterology · 2018 · phase 2A randomised, double-blind, sham-controlled trial, n=18

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What they asked

People admitted to hospital with a moderate to severe ulcerative colitis flare are usually treated with intravenous steroids. Around a third do not respond and need rescue therapy with infliximab or ciclosporin, or a colectomy. The investigators asked whether adding hyperbaric oxygen to standard intravenous steroids in the first days of admission was safe, feasible and able to improve early response, and whether this reduced the need for second-line treatment.

Who took part

Eighteen adults were randomised across several US academic hospitals: ten to hyperbaric oxygen plus steroids and eight to sham plus steroids. All had ulcerative colitis confirmed endoscopically and were hospitalised with a flare meeting standard severity criteria. People with contraindications to pressurisation, such as untreated pneumothorax, were excluded.

What they did

Everyone received intravenous steroids. The treatment group breathed 100 per cent oxygen at 2.4 atmospheres absolute for 90 minutes daily; the sham group sat in the same chamber breathing air at a minimal pressure designed to feel similar. Sessions ran for five days, with the option to continue to ten. Outcomes were clinical remission and response using standard scores at days 5 and 10, progression to second-line therapy during the admission, and inflammatory markers including CRP and faecal calprotectin. Assessors and participants were blinded.

What they found

At day 5, 50 per cent of the hyperbaric group were in clinical remission compared with none of the sham group (p = 0.04). By day 10, clinical response was 80 per cent versus 25 per cent and remission remained 50 per cent versus 0 per cent. Ten per cent of the hyperbaric group needed second-line therapy compared with 63 per cent of the sham group, and no one in the hyperbaric group had a colectomy during the admission versus 38 per cent in the sham group, a difference that did not reach statistical significance (p = 0.07). Inflammatory markers fell more in the treated group. No serious adverse events were attributed to the treatment.

Why it might work

Inflamed colonic mucosa is severely hypoxic, and that hypoxia sustains cytokine release and blocks repair. Delivering dissolved oxygen at high partial pressure into the bowel wall may interrupt this loop, dampen TNF-α and IL-6 signalling and support mucosal healing, mechanisms shown in animal colitis models.

Limits

Eighteen participants is very small, and the trial was designed as a pilot to establish feasibility rather than to prove efficacy. Confidence intervals around the effect sizes are wide. Follow-up covered the admission only, so durability beyond discharge is unknown. Sham chambers at minimal pressure can be imperfect blinds. Findings applied to a hospitalised population on intravenous steroids, not to outpatients with milder disease.

Paper 2

A phase 2B randomised trial of hyperbaric oxygen therapy for ulcerative colitis patients hospitalised for moderate to severe flares

Dulai et al. · Alimentary Pharmacology and Therapeutics · 2020 · phase 2B randomised trial comparing 3 versus 5 days of HBOT, n=20

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What they asked

Following the phase 2A pilot, the same group wanted to know how many sessions were needed. Was a shorter three-day course as effective as five days in producing early response in hospitalised ulcerative colitis, and did the benefit hold up to discharge and at three months? The design also allowed a pooled analysis with the earlier trial to give a clearer picture of the effect against sham.

Who took part

Twenty adults hospitalised with moderate to severe ulcerative colitis flares at US academic centres were enrolled and randomised to receive either three or five daily sessions of hyperbaric oxygen alongside intravenous steroids. The trial was planned as a larger study but was stopped early because of slow recruitment, so the analysis is smaller than intended.

What they did

All participants received 100 per cent oxygen at 2.4 atmospheres absolute for 90 minutes daily, in addition to standard intravenous steroids. One group stopped after three sessions, the other after five. Outcomes were clinical response and remission at day 5 and day 10, progression to second-line therapy, and outcomes at three months including steroid-free remission, readmission and colectomy. Data were pooled with the phase 2A trial to compare five days of treatment against sham across both studies.

What they found

Five sessions produced better results than three. In the pooled analysis, people who received five days of hyperbaric oxygen had a higher day 10 clinical remission rate and were less likely to need second-line rescue therapy during the admission than those receiving sham, with the day 5 response driving most of the benefit. Those treated for five days also had lower rates of readmission and colectomy at three months compared with the three-day group. Treatment was well tolerated, with ear discomfort the main complaint.

Why it might work

The dose-response pattern supports a biological effect rather than chance: more oxygen exposure gave more benefit, consistent with the time needed to reverse mucosal hypoxia, reduce inflammatory cytokines and allow epithelial repair to begin. Parallel translational work by the same group has described changes in mucosal neutrophil and T-cell populations after treatment.

Limits

The trial stopped early and enrolled only twenty people, so it was underpowered for its primary comparison. There was no sham arm within this trial; the comparison against sham relies on pooling with a separate earlier study. Three-month outcomes were exploratory. The setting was again acute hospital care, not maintenance or outpatient use.

Paper 3

Hyperbaric oxygen therapy for the treatment of perianal fistulas in 20 patients with Crohn's disease (HOT-TOPIC)

Lansdorp et al. · Alimentary Pharmacology and Therapeutics · 2021 · prospective interventional cohort, n=20 (one-year follow-up published in United European Gastroenterology Journal, 2022)

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What they asked

Perianal fistulas affect around a quarter of people with Crohn's disease and are among the hardest complications to treat: even with anti-TNF therapy and surgery, many tracts never close. The HOT-TOPIC investigators in Amsterdam asked whether a course of hyperbaric oxygen could improve fistula activity, measured clinically and on MRI, in people whose fistulas had failed conventional treatment.

Who took part

Twenty adults with Crohn's disease and perianal fistulas that had not responded to at least six months of standard treatment including anti-TNF therapy and, where appropriate, surgical drainage with setons. Median disease duration was over a decade. Participants continued their existing medication unchanged, and setons were removed shortly before treatment began.

What they did

Each participant received 40 sessions of hyperbaric oxygen at 243 to 253 kPa (around 2.4 to 2.5 ATA), each lasting about 110 minutes, delivered over roughly eight weeks. The primary outcome was change in the Perianal Disease Activity Index (PDAI) at week 16. Secondary outcomes included MRI scoring of the fistula tracts using a validated index, clinical closure of external openings, CRP and faecal calprotectin, and quality of life. A one-year follow-up paper reported durability at week 60.

What they found

Median PDAI fell significantly, from around 7.5 to 4 at week 16, and roughly 60 per cent of participants reached a PDAI of 4 or less, the threshold for inactive perianal disease. MRI scores improved, with some tracts becoming predominantly fibrotic. About two thirds had a clinical response and four participants achieved complete closure of all external openings. CRP and faecal calprotectin fell. At one year, most of the improvement was maintained. Middle-ear barotrauma was common, affecting around a third, with a few needing grommets; no other significant adverse events occurred.

Why it might work

A fistula tract is a chronic wound in hypoxic, infected tissue. Raising tissue oxygen supports fibroblast collagen synthesis and angiogenesis, restores oxygen-dependent bacterial killing by neutrophils, is directly hostile to anaerobes in the tract, and reduces the inflammatory cytokines that keep the tract open. The MRI shift towards fibrotic tracts is consistent with a true healing response.

Limits

This was an open-label cohort with no control group, so placebo effect and natural fluctuation cannot be excluded, though refractory fistulas rarely improve spontaneously. Twenty participants is small. Seton removal before treatment complicates interpretation. Ear barotrauma was frequent. Whether the benefit persists beyond one year, or how it compares with continued conventional therapy, is unknown.