When biologic therapies for ulcerative colitis fail, patients and physicians face a narrowing landscape of options. A new phase 2a pilot trial conducted in the Netherlands suggests that hyperbaric oxygen therapy (HBOT) may reopen a therapeutic window for some individuals with treatment-refractory disease, though researchers caution that larger studies are needed before any clinical recommendations can be made.
The Challenge of Refractory Colitis
Ulcerative colitis, a chronic inflammatory bowel disease (IBD), affects approximately 1 in 250 people in Western countries. While biologic agents such as anti-TNF drugs, integrin inhibitors, and IL-12/23 blockers have transformed care for many patients, roughly one-third either do not respond initially or lose response over time. For these individuals, the remaining options—surgery to remove the colon or experimental therapies—carry significant burdens.
The Dutch research team, enrolling patients between January 2023 and December 2024, set out to evaluate whether HBOT could offer a bridge to remission or stable disease in this difficult-to-treat population. Their hypothesis rested on a well-established mechanism: HBOT enhances tissue oxygenation, reduces inflammation, and promotes healing in hypoxic tissues—precisely the conditions found in active colitis lesions.
Study Design and Early Findings
The phase 2a trial employed a randomized, controlled design to test different HBOT regimens in patients whose disease had proven resistant to standard biologic therapy. Participants received hyperbaric oxygen at varying pressures and session frequencies, with researchers tracking clinical response, endoscopic healing, and quality-of-life measures.
While full results await peer-reviewed publication, preliminary findings presented to the research community indicate that a meaningful subset of participants achieved clinical stabilization during and immediately following HBOT treatment. Some patients showed improvements in endoscopic scores, suggesting that the therapy may promote mucosal healing in addition to symptom relief.
The study’s primary endpoint focused on safety and preliminary efficacy signals—exactly what a phase 2a trial is designed to establish. The research team reported that HBOT was generally well-tolerated, with no serious adverse events attributed to the therapy itself. Barotrauma, oxygen toxicity, and other known HBOT risks were monitored closely and remained within expected ranges for this patient population.
Why HBOT Might Work in Colitis
The scientific rationale for HBOT in inflammatory bowel disease draws on decades of research into tissue hypoxia and chronic inflammation. In active colitis, the intestinal lining becomes severely hypoxic due to increased oxygen demand from immune cells and compromised blood flow. This hypoxia perpetuates a cycle of inflammation and tissue damage.
HBOT delivers 100% oxygen at pressures typically 2.0 to 2.4 atmospheres absolute (ATA), dramatically increasing the amount of dissolved oxygen in plasma. This super-saturated oxygen can reach tissues even when blood flow is compromised, potentially breaking the inflammatory cycle. Additionally, HBOT has been shown to reduce levels of pro-inflammatory cytokines and promote angiogenesis—new blood vessel formation that could restore healthy tissue perfusion.
Previous case series and small observational studies have suggested benefit in severe colitis, particularly as an adjunct to conventional therapy. The Dutch trial represents the first randomized, controlled investigation specifically in the biologic-refractory population, a group with particularly high unmet need.
The FDA Perspective: Not a Cleared Indication
Despite these promising early signals, it is essential to understand the regulatory context. The U.S. Food and Drug Administration has not cleared HBOT for the treatment of ulcerative colitis, Crohn’s disease, or any other inflammatory bowel condition. The agency’s approved indications for HBOT remain limited to specific conditions including decompression sickness, carbon monoxide poisoning, certain non-healing wounds, and late radiation tissue injury.
In its August 2025 safety communication, the FDA specifically warned against using HBOT for unproven indications outside of controlled clinical trials. The agency emphasized that while research should continue, patients should not seek HBOT for colitis or other unapproved uses expecting established benefit.
This regulatory stance reflects the reality that early-phase trials, while encouraging, do not establish efficacy. Phase 2 studies are designed to refine dosing, identify signals of activity, and guide the design of definitive phase 3 trials—not to change clinical practice. The Dutch researchers themselves have indicated that a larger, multicenter phase 3 trial would be necessary before any regulatory submission could be considered.
What This Means for Patients
For individuals living with treatment-refractory ulcerative colitis, news of any potential new therapy brings hope—but also the risk of misplaced expectations. The current evidence for HBOT in colitis remains preliminary. Patients should not pursue HBOT outside of clinical trials based on these early results.
That said, the research does open important possibilities. If confirmed in larger studies, HBOT could represent a non-pharmacological option for patients who have exhausted biologic therapies and wish to delay or avoid surgery. The therapy’s established safety profile in other indications, combined with its mechanism of promoting tissue healing, makes it a plausible candidate for further investigation.
Patients interested in exploring this avenue should discuss clinical trial opportunities with their gastroenterologist. Several academic medical centers in the United States and Europe are reportedly considering participation in expanded HBOT-colitis trials based on these Dutch findings.
The Road Ahead
The Dutch phase 2a trial adds to a growing body of research exploring HBOT applications beyond traditional indications. From traumatic brain injury to long COVID, researchers are testing whether enhanced oxygen delivery can modulate inflammation and promote healing in conditions where hypoxia plays a central role.
For the colitis community specifically, the next steps are clear: a phase 3 randomized controlled trial with adequate statistical power to detect meaningful differences in remission rates, endoscopic healing, and quality of life. Such a trial would need to compare HBOT against continued standard care or placebo, with long-term follow-up to assess durability of response.
If successful, this research trajectory could eventually lead to FDA submission and, potentially, a new indication for HBOT. Until then, the therapy remains an investigational approach for colitis—promising enough to pursue rigorously, but not established enough to recommend outside research settings.
The investigators have indicated they plan to publish full results in a peer-reviewed gastroenterology journal later this year, which should provide more detailed data on response rates, optimal dosing regimens, and patient selection criteria. For now, the medical community watches with cautious interest as another potential tool against refractory inflammatory bowel disease moves through the scientific validation process.