A General Overview on the Hyperbaric Oxygen Therapy: Applications, Mechanisms and Translational Opportunities Original paper

What was reviewed?

This review examined the biological mechanisms, clinical applications, and translational potential of hyperbaric oxygen therapy (HBOT), a treatment that delivers 100% oxygen under elevated atmospheric pressure to increase oxygen availability in tissues. The authors analyzed how HBOT improves oxygen diffusion, enhances angiogenesis, regulates immune responses, and exerts antimicrobial effects, and they evaluated its approved clinical uses in infections, wound healing, hypoxia-related conditions, and emergency settings. The review also explored emerging roles in inflammatory diseases, cancer therapy, and viral infections, emphasizing its molecular effects on reactive oxygen species (ROS), hypoxia-inducible factor (HIF) signaling, and tissue repair pathways.

Who was reviewed?

The review synthesized findings from clinical studies, animal experiments, and mechanistic cellular research involving patients with hypoxic conditions, chronic wounds, infections such as Clostridial myonecrosis, ischemic injuries, inflammatory disorders, and malignancies. It also examined experimental models evaluating HBOT effects on immune cells, endothelial cells, microbial biofilms, and hypoxic tumor environments. This included both human clinical populations undergoing HBOT and laboratory models designed to investigate microbial response, angiogenesis, inflammatory signaling, and oxygen-dependent metabolic changes.

What were the most important findings?

HBOT increases oxygen dissolved in plasma independently of hemoglobin, allowing oxygen to reach hypoxic tissues even when circulation or oxygen transport is impaired, thereby reversing hypoxia and restoring metabolic function. This elevated oxygen availability enhances mitochondrial respiration, reduces ischemic injury, and improves tissue survival in hypoxic microenvironments. Importantly, HBOT exerts strong microbiome-relevant antimicrobial effects by inhibiting anaerobic bacterial growth, especially Clostridium species, which require low-oxygen environments to proliferate and produce toxins. HBOT disrupts bacterial biofilms, enhances neutrophil-mediated microbial killing, and increases antimicrobial peptide production, shifting the microbiome balance away from pathogenic anaerobes and reducing infection severity. A General Overview on the Hyper…

HBOT also enhances angiogenesis and tissue repair through upregulation of vascular endothelial growth factor (VEGF), nitric oxide signaling, and endothelial progenitor cell recruitment, promoting vascular regeneration in chronic wounds and ischemic tissues. These effects alter local microbiome-host interactions by improving tissue oxygenation, which suppresses anaerobic pathogens while favoring aerobic commensals. Additionally, HBOT modulates immune responses by decreasing pro-inflammatory cytokines such as IL-6 and TNF-α while regulating lymphocyte activity and macrophage function, improving host microbial control and reducing chronic inflammation. Mechanistically, HBOT increases ROS and reactive nitrogen species, which act as signaling molecules that stimulate immune activation, angiogenesis, and microbial killing, while also activating transcription factors such as HIF that regulate cellular adaptation to oxygen changes.

What are the greatest implications of this review?

HBOT represents a powerful adjunct therapy that directly modifies tissue oxygen levels to influence host-microbiome interactions, immune function, and pathogen survival, making it especially valuable for treating anaerobic infections, chronic wounds, and necrotizing soft-tissue infections. By restoring oxygen availability, HBOT shifts microbial ecosystems away from anaerobic pathogenic dominance, enhances immune clearance, and accelerates tissue regeneration. These microbiome-relevant effects suggest HBOT could serve as an important tool for managing dysbiosis-associated infections and hypoxia-driven inflammatory conditions. Its ability to modulate host immune responses, improve vascularization, and suppress anaerobic pathogen proliferation positions HBOT as a promising adjunctive treatment in infectious disease, inflammatory disorders, and oncology. However, further clinical studies are needed to optimize patient selection, dosing protocols, and integration with microbiome-targeted therapies.