Hyperbaric oxygen therapy: effects on IBD and the gut microbiome

A promising but nuanced story

Hyperbaric oxygen therapy (HBOT), a treatment involving exposure to pure (100%) oxygen in a pressurized chamber, is gaining attention for its potential to treat inflammatory conditions and promote tissue healing. But is all that oxygen good for the gut? In this post, I discuss the effects of HBOT on the gut, including its remarkable effects in inflammatory bowel disease (IBD) and some potential concerns when it comes to the gut microbiome.

The Remarkable Promise of HBOT in Inflammatory Bowel Disease

The therapeutic use of HBOT in IBD has been supported by studies showing remarkable effects. A 2022 systematic review (including 3 randomized controlled trials and 16 case series of HBOT in IBD) estimated that 88 percent of patients with luminal Crohn’s disease and 87 percent of patients with ulcerative colitis achieved clinical remission using HBOT.

These studies typically involved exposure to 100% oxygen at pressures of 2.0–2.5 atmospheres absolute (ATA) for 90–120 minutes per session. The protocols involved multiple sessions per week and typically ranged from 10 to 40 sessions depending on disease severity​​. The therapy was safe and well tolerated, with minor adverse effects reported in only 15 percent of patients​.

While more controlled studies are needed to confirm these findings, these results are very promising. The beneficial outcomes likely stem from HBOT’s ability to reduce tissue hypoxia, stimulate wound healing, and enhance immune modulation. By increasing tissue oxygenation, HBOT promotes antimicrobial pathways and tissue repair—key factors in the management of chronic inflammation​.

A Double-Edged Sword: HBOT and Gut Microbiota

But if you’ve read my article on the oxygen-gut dysbiosis connection, you might be (rightly) asking: Isn’t more oxygen in the gut bad?

Indeed, the healthy colonic lumen (i.e. the primary site of the gut microbiome) is an extremely low-oxygen environment. This low oxygen helps to promote the growth of beneficial, oxygen-intolerant bacteria like butyrate-producers and suppress the growth of more oxygen-flexible pathogens, like Escherichia, Klebsiella, and Candida.

A recent study in mice treated with HBOT showed that while gut tissue oxygenation improved (a good thing, beneficial for healing), the therapy disrupted the low-oxygen environment of the gut lumen (not good). This led to gut dysbiosis, characterized by reduced levels of short-chain fatty acids like butyrate, and increased susceptibility to pathogenic C. difficile infection.

This raises the question: How can a therapy that appears to disrupt the gut microbiota yield such positive outcomes in IBD?

The answer lies in understanding the gut environment.

The Gut Environment: A Key Driver of Health and Dysbiosis

I’ve discussed before how the gut environment—including oxygen levels, pH, nutrient availability, and immune status—is crucial to shaping the microbial ecosystem. In IBD, the environment is one of chronic inflammation, which already serves to oxygenate the gut, damage the gut barrier, and promote the growth of pro-inflammatory microbes like Escherichia coli.

HBOT’s effects may temporarily oxygenate the gut lumen, disadvantaging beneficial anaerobes, but by reducing inflammation and restoring gut barrier function, it creates conditions for the long-term recovery of a healthier, hypoxic gut environment. This highlights a critical point: treating the environment is often more important than directly targeting the microbiota itself.

Thus, HBOT’s greatest strength likely lies in its ability to shift the environment back into balance by reducing inflammation.

Indeed, one exploratory trial in Crohn’s disease found that HBOT enhanced gut microbial diversity, whilst reducing markers of systemic inflammation. Key changes included a decrease in Escherichia — a genus linked to inflammation — and increases in beneficial microbes like Bifidobacterium and the butyrate-producing group Clostridium XIVa.

Weighing the Tissue vs. Microbiota Trade-Off

In diseases like IBD, the epithelium is so damaged that restoring its integrity is likely a critical first step, and HBOT can be a part of that healing. Once the epithelial barrier is intact and inflammation is reduced, any microbiota disruption may self-correct over time or be further modulated with targeted interventions.

In other cases, where gut inflammation is not as significant, it’s unclear if the benefits of HBOT outweigh the potential adverse effects on colonic oxygenation and the microbiota. The effects of HBOT on the gut have yet to be tested in cases of irritable bowel syndrome, or other chronic conditions characterized by gut dysbiosis and minimal or low-grade inflammation.

Future studies will hopefully monitor both short- and long-term effects of HBOT on the microbiota and clinical outcomes in these different populations.

The Potential Role of Butyrate in Mitigating HBOT Effects on the Microbiota

If you do plan to undergo HBOT though, supplement with butyrate! Butyrate plays a pivotal role in gut health by supporting epithelial barrier function and immune regulation. And, in the study I mentioned above where HBOT led to dysbiosis and increased the risk of C. difficile infection, treating mice with butyrate during HBOT was largely protective.

Supplementation with butyrate could therefore act as an adjunct therapy to mitigate HBOT-induced dysbiosis.

For a deeper dive into the significance of butyrate and other SCFAs, check out my earlier post, "The Oxygen-Gut Dysbiosis Connection", where I discuss their intricate roles in maintaining gut and immune health.

Summary & Takeaways

HBOT holds great promise for treating IBD, with limited high quality evidence but thus far remarkable results. It has not yet been studied in irritable bowel syndrome or cases of dysbiosis without significant inflammation.

To optimize its therapeutic potential, clinicians and researchers should carefully weigh the benefits of HBOT against the risks of disrupting gut microbial homeostasis: Those with active inflammation or who are in need of tissue repair are highly likely to benefit, whereas those without significant inflammation may do more harm than good.

Combining HBOT with microbiota-supportive interventions, such as butyrate supplementation, could allow for safer and more effective treatments, maximizing the benefits of HBOT while minimizing any negative impact on overall gut health.

And of course, all of this highlights again the importance of the gut environment for improving the health of the gut microbiome.

That’s all for now. If you’ve tried HBOT, I’d love to hear your experience in the comments below!