A long time ago, ancient fish swam in a harsh aquatic environment, with scarce light and limited oxygen. Many died but some survived and evolved, eventually giving rise to Misgurnus anguillicaudatus — a type of loach fish common in parts of East Asia. The loach fish’s secret survival mechanism? A unique form of intestinal breathing via their posterior.
In other words: loach fish breathe through their butt. But scientists now report this evolutionary breathing mechanism may not be limited to fish.
Turns out certain mammals can also breathe through their intestines using a process researchers describe as “enteral ventilation via anus.” The breathtaking finding is described in a new paper published on Friday in the journal CellPress.
There’s also a timely reason for researchers to explore this technology: Covid-19. The study team argues the method explored here could eventually be used to help humans experiencing lung failure. This intestinal breathing technique, facilitated by external ventilation, could aid patients failed by or without access to current tools like ventilators.
What’s new — For the first time, researchers have proof that intestinal breathing can occur in mammals — albeit, with a little intervention.
When the research team injected either gaseous or liquid oxygen into the rectums of both rodents and pigs, a procedure known as enteral ventilation via anus (EVA), they found the animals were capable of intestinal breathing.
In fact, the procedure boosted oxygen levels in animals experiencing oxygen deprivation, increasing their chances of survival.
“A proof-of-principle EVA approach is effective in providing [oxygen] and alleviating respiratory failure symptoms in two mammalian model systems,” the team writes.
The animals experienced no apparent side effects from the somewhat unorthodox treatment.
The controversy — The fact that land-based mammals and aquatic species share the capacity for this breathing is a remarkable finding for evolutionary biology. But it’s a pretty controversial idea within the medical research community, according to the scientists.
Previous research suggests oxygen infusion from this type of procedure may help children experiencing lung failure, but not all scientists agreed with these conclusions. Furthermore, researchers don’t agree on what part of the gut is most important for intestinal breathing.
“We speculate that [other researchers] are mostly focused on upper GI tract — such as stomach, small intestine — whereas our protocol focused on GI tract, most remarkably the rectum as the main site for breathing,” lead author Takanori Takebe, of the Tokyo Medical and Dental University and the Cincinnati Children's Hospital Medical Center, tells Inverse.
How it works — It sounds stranger than fiction: Scientists helped pigs and rodents breathe through their gut by inserting oxygen into animal’s butts via an enema.
Takebe breaks down what it likely looks like when mammals breathe using this little-understood intestinal mechanism:
- Scientists deliver oxygen gas or liquid oxygen — perfluorocarbon — to the animal’s rectum via the EVA method.
- Scientists deprive the animal’s bodies of oxygen. Critically, the oxygen provided during EVA helps keep these animals alive in these hypoxic conditions, circulating around the rectum and gut.
- An exchange of gases — oxygen and carbon dioxide — occurs, as would normally happen during breathing. Oxygen and carbon dioxide travel between the lungs, bloodstream, and heart, supplying the body with oxygen.
Finally: When using liquid oxygen, some liquid will then be excreted from the anus. This procedure can get a little messy.
The researchers tested their experiment on mice and pigs to confirm intestinal breathing could work in mammals of different sizes — and it did.
In mice, the researchers found that they were able to reverse hypoxia for 60 minutes — possibly a life-saving amount of time. The scientists also used control groups — animals that did not receive the EVA — to confirm that their treatment improved the animal’s oxygen levels.
For example, two mice — one that had received the EVA and one that did not — walked side by side. The EVA-treated mice had a “statistically significant” increase in oxygen compared to the mice that did not receive the treatment.
Why it matters — The researchers weren’t just poking around animal butts for fun or to simply confirm an evolutionary hunch. They were hoping to harness techniques that could one day treat lung failure in humans.
Previous research has used perfluorochemicals to treat lung injuries, a technique underlying what’s known as “liquid ventilation,” but this new study paves the way for a broader application of EVA to help humans in respiratory distress.
“Due to ease of the method — simple enema — it can be potentially used even at an understaffed hospital which is not able to use high-end medical procedures such as a ventilator or ECMO (extracorporeal membrane oxygenation),” Takebe says.
“We can potentially develop a new medical device, aimed at increasing oxygen level in humans.”
Patients suffering from severe Covid-19 are often placed on ventilators or may undergo ECMO, requiring doctors to pump and oxygenate a patients’ blood using a machine.
But during times of peak Covid-19, ventilators and ECMO machines fall into short supply. This intestinal breathing technique, facilitated by external ventilation, could potentially work as an alternative treatment for Covid-19 patients, Takebe says.
“We can potentially develop a new medical device, aimed at increasing oxygen level in humans,” he says. “If granted, clinicians can explore the option to support respiratory complications associated with many infectious diseases including COVID-19.”
What’s next — The study holds promise for future medical treatments, but scientists still need to answer three questions before we can implement these treatments in human patients.
- The researchers note that it’s not totally clear what’s happening with oxygenation in the gut. The team found proof of gas exchange of oxygen and carbon dioxide in the animal’s “rectal region” but we don’t entirely know why that exchange is occurring.
- While the study team acknowledges the promising potential of this gas exchange mechanism to help with respiratory failure related to oxygen deprivation, they’d like to explore other health issues it could treat. These issues include severe pneumonia and acute respiratory distress syndrome (ARDS), which occurs when fluid leaks into the lungs.
- It may be one thing to conduct an experimental procedure on a rat or a pig, but many more steps need to be taken to before we can safely guarantee humans can undergo similar treatment without any serious side effects.
Especially when it comes to novel treatments in the derriere.
Background: Several aquatic organisms such as loaches have evolved unique intestinal breathing mechanisms to survive under extensive hypoxia. To date, it is highly controversial whether such capability can be adapted in mammalian species as another site for gas exchange. Here, we report the advent of the intestinal breathing phenomenon in mammalians by exploiting EVA (enteral ventilation via anus).
Methods: Two different modes of EVA were investigated in an experimental model of respiratory failure: intra-rectal oxygen O2gas ventilation (g-EVA) or liquid ventilation (l-EVA) with oxygenated perfluoro-carbon. After induction of type 1 respiratory failure, we analyzed the effectiveness of g-EVA and I-EVA in mouse and pig, followed by preclinical safety analysis in rat.
Findings: Both intra-rectal O2gas and oxygenated liquid delivery were shown to provide vital rescue of experimental models of respiratory failure, improving survival, behavior, and systemic O2level. A rodent and porcine model study confirmed the tolerable and repeatable features of an enema-like l-EVA procedure with no major signs of complications.
Conclusions: EVA has proven effective in mammalians such that it oxygenated systemic circulation and ameliorated respiratory failure. Due to the proven safety of perfluorochemicals in clinics, EVA potentially provides an adjunctive means of oxygenation for patients under respiratory distress conditions.