On a good day, things exit through the anus. But in rodents and pigs in respiratory distress, oxygen can be absorbed by tissues in the rectum, helping the animals recover, a new study suggests. The scientists behind the research propose that flushing oxygen into the rectum could one day help save human lives if conventional ventilation methods are unavailable.

"It looks like a crazy idea," says Sean Colgan, a gastroenterologist at the University of Colorado, Boulder, who was not involved in the study. "But if you look at the data, it's actually a very compelling story."

Most mammals breathe through their mouths and noses and send oxygen to their body via the lungs. A few aquatic animals, including sea cucumbers and catfish, breathe through their intestines, and the intestinal tissues of humans can readily absorb pharmaceuticals. But no one knew whether oxygen could enter the bloodstream via mammalian intestines.

To find out, Takanori Takebe, a gastroenterologist from Cincinnati Children's Hospital, and his colleagues tested several approaches to ventilating the intestines of mice and pigs that were deprived briefly of oxygen. In one group of 11 mice, four had their intestines scrubbed to thin the mucosal lining and improve oxygen absorption. Next, the researchers injected pure, pressurized oxygen into the rectums of the scrubbed mice and four of the seven unscrubbed ones.

Then, the researchers withdrew oxygen from the animals, making them "hypoxic." The three unscrubbed mice that received no intestinal oxygen survived for a median of 11 minutes. Mice with unscrubbed intestines that received oxygen through their anuses lasted 18 minutes. Only the ventilated mice with brushed intestines lived through the hourlong experiment, with a survival rate of 75%, the researchers report today in Med.

But Takebe and colleagues wanted to ditch the onerous—and dangerous—process of intestinal scrubbing. So they replaced the pressurized oxygen with fluids known as perfluorocarbons, which can carry large amounts of oxygen and are often used as a substitute for blood during surgery. Because they are highly dense, perfluorocarbons can also help flush mucus out of the intestine. The researchers injected oxygen-rich perfluorocarbons into the anuses of three hypoxic mice and seven hypoxic pigs; as a control, they flushed saline solution into the intestines of two hypoxic mice and five hypoxic pigs.

Whereas blood-oxygen levels in the control groups plummeted, oxygen levels in the ventilated mice steadied to normal levels. In the treated pigs, blood oxygen saturation increased by about 15%, relieving them of hypoxic symptoms. Color and warmth returned to their skin and extremities in minutes.

The two findings, Takabe says, are proof that mammals can absorb oxygen through their intestines—and that their new "weird approach" is safe. The new method will need to undergo safety testing in people, but Takebe says he can envision injecting oxygen-loaded fluids through the anus to help save human lives when standard ventilation methods are unavailable, as for example, during the recent coronavirus pandemic.

Even if it proves safe, oxygen ventilation through the anus may not be particularly effective, says Markus Bosmann, a pulmonologist at the Boston University School of Medicine who was not involved in the study. He would like to see scientists compare the technique with conventional respiratory treatments such as mechanical ventilation. Colgan agrees more testing is needed, and notes that if anal ventilation were ever used with patients, it would likely have to be short lived. Introducing oxygen to the intestines would probably kill the microbes involved in digestion, he says.

Theoretically, though, there shouldn't be long-lasting effects from enteral ventilation, says Caleb Kelly, a gastroenterologist from the Yale School of Medicine who peer-reviewed the paper. Of course, that will need to be demonstrated with experiments, he says. "[But] they may be able to show that in the right setting, it's effective."