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New research in animals explores a potential new treatment for respiratory failure. Image credit: Getty Images
  • A new study finds that rodents and pigs can use their intestines for respiration.
  • By delivering oxygen gas or oxygenated liquid through the anus, the researchers reversed symptoms of respiratory failure in mice and pigs.
  • The findings could pave the way for new emergency treatments to support critically ill people when mechanical ventilation is unavailable or unsuitable.
  • The researchers hope to progress their research and explore the clinical use of this process in humans.

Rodents and pigs can effectively breathe through their intestines, according to a new study.

The researchers managed to rescue pigs and mice from respiratory failure by delivering oxygen through the rectum.

These findings could pave the way for new therapies to keep the body oxygenated when the lungs fail and mechanical ventilation is unavailable.

"Artificial respiratory support plays a vital role in the clinical management of respiratory failure due to severe illnesses such as pneumonia or acute respiratory distress syndrome," says senior study author Dr. Takanori Takebe, who works at the Tokyo Medical and Dental University and the Cincinnati Children's Hospital Medical Center.

"Although the side effects and safety need to be thoroughly evaluated in humans, our approach may offer a new paradigm to support critically ill patients with respiratory failure," Dr. Takebe adds.

The study appears in the journal Med .

Several aquatic organisms have adapted to survive in low oxygen environments by evolving alternative breathing mechanisms alongside lungs or gills. For instance, loaches, sea cucumbers, some freshwater catfish, and stretch spiders all use their lower intestines for respiration.

However, until now, whether mammals have similar capabilities has remained a mystery.

"This is [the] first [study] to our knowledge to show successful repurposing of the distal gut for breathing apparatus inspired by aquatic organisms," Dr. Takebe told Medical News Today. "We are all surprised that [the] intestinal breathing capacity that the loaches have is maintained even in mammalian species such that [it] is sufficient for rescuing [from] lethal hypoxia/asphyxia condition[s]."

Dr. Takebe and his team used pig and rodent animal models to provide evidence of intestinal breathing in mammals.

First, they designed an intestinal gas ventilation system that delivered pure oxygen gas through the rectum of mice in an enema-like procedure.

They then exposed the mice to extremely low oxygen conditions. Without the intestinal ventilation system, none of the animals survived as long as 11 minutes. Administering oxygen gas through the anus increased the median survival of the mice to 18 minutes.

However, the system was most effective when researchers made a small abrasion in the intestinal mucous membrane. This abrasion allowed for more efficient movement of gas between the intestine and surrounding blood vessels. Of the mice with intestinal abrasion and gas ventilation, 75% survived for 50 minutes in conditions that would normally be lethal.

As the intestinal gas ventilation system requires damage to the intestinal mucosa, it is unlikely to be feasible for clinical use in humans — especially in severely ill people.

Due to this, the researchers developed an alternative solution that uses an oxygenated liquid called perfluorodecalin (PFD) and does not require abrasion of the intestinal mucus layer.

PFD belongs to a group of substances called perfluorochemicals, which studies have shown to be clinically safe in humans. PFD has a notably high adsorbing capacity for oxygen and carbon dioxide, and previous clinical trials have tested the use of perfluorochemicals as a substitute for blood.

Following treatment with intestinal liquid ventilation, the mice in the test group could walk significantly farther than those in the control group, and more oxygen reached their hearts.

The researchers also tried pumping repeated cycles of PFD into the intestines of pigs. They found that the treated animals had higher oxygen levels than those that did not receive treatment. Moreover, the treatment reversed the symptoms of skin pallor and coldness that arose from lack of oxygen.

The study demonstrates an effective mechanism of circulating oxygen and relieving symptoms of respiratory failure in two mammalian species.

The next step, Dr. Takebe says, is for the researchers to expand their studies to evaluate mid-to-long-term safety before accelerating the path to human clinical trials.

However, there may be a few bumps in the road, according to Dr. Caleb Kelly, a clinical fellow at Yale School of Medicine in New Haven, CT, who was not involved in the study.

"[The] initial perception of [intestinal ventilation] is likely to parallel that of fecal microbiota transplant […], which not long ago was deemed untenable for 'practical and aesthetic reasons,' but now has less stigma as data supporting effectiveness are overwhelming," Dr. Kelly writes in a separate viewpoint article that also features in Med.

If intestinal ventilation can overcome this stigma, researchers believe that it could one day serve as an alternative form of artificial respiratory support for critically ill people.

"For most patients, mechanical ventilation is adequate for delivery of oxygen and removal of carbon dioxide from circulation," says Dr. Kelly. "However, in some situations faced by first responders, mechanical ventilation is not available. Further, the current pandemic has demonstrated that mechanical ventilators are a finite resource."

Dr. Takebe agreed that COVID-19 has demonstrated the need for new life support technologies but warned that his team "needs to cautiously evaluate the safety of the process, as COVID-19 has [a] very complicated pathogenesis."

MNT also reached out to Prof. Michael Steiner of the University of Leicester in the United Kingdom, who is a consultant respiratory physician. When we asked how relevant these findings are to the ongoing COVID-19 pandemic and the associated requirement for ventilators, Prof. Steiner replied: "Very limited. [This is] early stage research. [The findings] won't be relevant to [the] current pandemic, and [it is] unclear if [they] will turn out to be a viable strategy."

However, the study's senior author remains optimistic about the use and relevance of the findings:

"The recent SARS-CoV-2 pandemic is overwhelming the clinical need for ventilators and artificial lungs, resulting in a critical shortage of available devices and endangering patients' lives worldwide. The level of arterial oxygenation provided by our ventilation system, if scaled for human application, is likely sufficient to treat patients with severe respiratory failure, potentially providing lifesaving oxygenation."

– Dr. Takanori Takebe