In a medical breakthrough that sounds more like science fiction than reality, researchers have successfully demonstrated the safety of a radically unconventional method to oxygenate the human body—enteral ventilation. This pioneering approach involves delivering oxygen through the colon using a super-oxygenated liquid, offering a potential lifeline for patients whose airways are blocked or whose lungs are severely compromised. The concept challenges traditional respiratory support mechanisms and opens a new frontier in emergency and critical care medicine.
Enteral ventilation, as explored in a recently published first-in-human clinical trial led by Dr. Takanori Takebe and colleagues, capitalizes on the colon’s rich vascular network and absorptive capacity. Instead of relying solely on pulmonary gas exchange, this innovative technique delivers oxygen-rich perfluorocarbon liquid intrarectally, enabling oxygen absorption through the gut lining directly into the bloodstream. This concept was rigorously tested for safety in healthy volunteers, marking an important milestone towards clinical application.
The clinical trial, conducted in Japan and published in the journal Med in October 2025, recruited twenty-seven healthy male participants who were asked to retain varying volumes of perfluorodecalin—a highly oxygen-permeable fluorocarbon compound used as the oxygen-transport medium—inside the rectum for up to sixty minutes. The trial was meticulously designed to evaluate tolerability and adverse effects without using oxygenated liquid initially, laying a foundational understanding of physiological responses to intrarectal liquid retention.
Remarkably, most participants successfully held volumes up to 1,500 milliliters of this liquid for the full duration. While some reported mild abdominal bloating and discomfort at larger volumes, there were no serious adverse events, indicating that the intervention is generally safe and tolerable. This early safety profile paves the way for subsequent studies that will employ fully oxygenated perfluorocarbon liquids to test the efficacy and quantifiable oxygen uptake in human subjects.
The genesis of this extraordinary therapy draws inspiration from nature. The loach fish, capable of supplementing its oxygen requirements by gulping air and absorbing oxygen through its gut lining, provided a biological blueprint. This evolutionary adaptation illustrates that non-pulmonary oxygen absorption is feasible and efficacious, an insight that helped shape the hypothesis behind enteral ventilation.
Moreover, the concept is rooted in prior scientific advances in oxygen therapeutics, specifically the development of perfluorocarbon liquids like Oxycyte by Leland Clark, a pioneer in artificial blood research. Although earlier applications of these liquids as oxygen carriers faced significant hurdles, their remarkable oxygen solubility and inert characteristics rendered them ideal candidates for this new mode of oxygen delivery.
Medically, enteral ventilation could revolutionize respiratory support by providing an alternative oxygenation route when conventional ventilation fails or is impractical. This includes scenarios such as airway obstruction due to trauma, severe pulmonary infections causing ventilation-perfusion mismatch, or situations where mechanical ventilation is contraindicated. Its minimally invasive nature and reliance on a relatively low-tech infrastructure enhance its appeal for emergency medicine and resource-limited settings.
From a technical perspective, perfluorodecalin’s physicochemical properties are critical to the success of enteral ventilation. This fluorinated liquid dissolves oxygen at concentrations significantly higher than plasma, facilitating rapid diffusion across the colonic mucosa into surrounding capillaries. The liquid’s density also prevents it from quickly passing through the colon, allowing sustained oxygen delivery during retention intervals.
The next phase of research will involve administering the oxygenated perfluorocarbon liquid and monitoring systemic oxygenation through serial blood gas analyses. This will help determine optimal dosing volumes and retention times necessary to achieve clinically significant increases in blood oxygen levels. Success in these trials will validate the concept’s therapeutic potential and inform protocols for emergency and intensive care deployment.
In addition to emergency applications, the researchers envisage extending enteral ventilation technology to vulnerable populations such as neonates. Newborns with compromised pulmonary function could benefit immensely from an additional oxygen delivery pathway that bypasses damaged lung tissue and supports oxygenation without intubation or extracorporeal membrane oxygenation (ECMO), devices often associated with high morbidity risks.
While enteral ventilation is still in its infancy, the scientific community is watching its progression closely. The establishment of EVA Therapeutics, a company founded by Dr. Takebe to further advance this technology, signifies a committed translation of bench research into bedside therapy. However, the pace of clinical development and availability of treatments will depend heavily on continued funding and regulatory approvals.
This innovation, which earned Takebe and his team an IgNobel Prize in 2024 for “butt breathing,” highlights the thin line between unconventional research and transformative medical progress. As the trials advance from demonstrating safety to proving efficacy, enteral ventilation could become a vital tool parked alongside conventional respirators in hospitals worldwide.
The proof-of-concept successfully documented to date reignites interest in non-traditional respiratory support strategies, challenging centuries of medical orthodoxy. If future studies confirm that rectally delivered oxygen can meaningfully augment oxygenation and improve patient outcomes, enteral ventilation might not only save lives in critical emergencies but also redefine how we conceptualize respiratory assistance altogether.
Subject of Research: People
Article Title: Safety and tolerability of intrarectal perfluorodecalin for enteral ventilation in a first-in-human trial
News Publication Date: 20-Oct-2025
Web References:
– Journal Article DOI: http://dx.doi.org/10.1016/j.medj.2025.100887
– Original research in porcine model: https://www.sciencedirect.com/science/article/pii/S2666634021001537
– The Nature of Things feature: https://www.imdb.com/title/tt31031863/
– IgNobel Prize announcement: https://scienceblog.cincinnatichildrens.org/ig-nobel-prize-awarded-to-takanori-takebe-for-butt-breathing-study/
Image Credits: Cincinnati Children’s and the journal Med
Keywords: Health and medicine, Emergency medicine, Gastroenterology, Neonatology
