Gut microbes: the secret to squirrel hibernation

A ground squirrel in hibernation
Photo Credit: Matthew Regan

Scientific Frontline: Extended "At a Glance" Summary: Host-Microbiome Urea Salvage in Hibernation

The Core Concept: Gut microbes play an essential symbiotic role in enabling hibernating mammals to survive prolonged periods of fasting by salvaging elemental carbon and nitrogen from bodily waste. This microbial process converts metabolic waste into life-sustaining nutrients, compensating for the complete lack of dietary intake during winter dormancy.

Key Distinction/Mechanism: Unlike non-hibernating animals that excrete urea through the bladder as urine, ground squirrels reroute urea into their intestines during hibernation. There, specialized gut bacteria equipped with unique enzymes break down the urea, extracting carbon to synthesize acetate—a critical biomolecule that the squirrel's body then absorbs and utilizes to sustain cellular function and preserve muscle mass.

Major Frameworks/Components: 

• Host-Microbiome Mutualism: The symbiotic adaptation where an animal's physiology actively shifts to maximize the utility of microbial metabolic byproducts.
• Microbial Acetogenesis: The specific biochemical pathway in which gut microbes extract carbon from urea to produce acetate.
• Urea Carbon and Nitrogen Salvage: The rerouting and repurposing of urea to preserve essential proteins and cellular building blocks in the absence of dietary input.
• Isotopic Tracing Methodology: The use of carbon-13 isotopes injected into test subjects to definitively track the metabolic conversion of urea into biologically usable acetate.

Branch of Science: Zoology, Microbiology, and Animal Physiology. 

Future Application: Understanding this biological recycling mechanism presents highly promising pathways for mitigating sarcopenia (age-related muscle loss) and treating severe muscle atrophy resulting from malnutrition, illness, or the microgravity conditions experienced by astronauts during long-duration spaceflight.

Why It Matters: This discovery illustrates a profound biological paradigm wherein extreme survival is achieved through the near-perfect recycling of existing internal resources rather than external consumption. Harnessing this evolutionary adaptation could revolutionize clinical approaches to protein balance and muscle preservation in human medicine and space exploration.

Matthew Regan, professor in the Department of Biological Sciences at Université de Montréal
Photo Credit: Matthew Regan

When winter sets in and food becomes scarce, some mammals hibernate, entering a state of deep rest that slashes their energy needs and allows them to fast for months.  

However, fasting deprives them of essential nutrients, including carbon. Carbon, the building block of all life, normally comes from food. But hibernating animals take in no carbon, while their bodies keep releasing it through respiration, mostly as carbon dioxide. 

So where does the carbon needed to sustain their cells through the long winter come from? 

A new study led by Matthew Regan, a professor at Université de Montréal’s Department of Biological Sciences, points to an unexpected source: the gut microbiome. 

Carbon recycling in nature 

Regan’s team focused on the ground squirrel, a hibernator from the marmot family (not the urban squirrels that populate Montreal’s parks). The scientists uncovered a remarkable survival strategy: the squirrels’ gut microbes salvage carbon from urea; a waste product usually flushed out in urine. 

Instead of being excreted through the bladder, the squirrels' urea is rerouted to their intestines. There, microbes equipped with enzymes not found in vertebrates break it down and repurpose the carbon to create acetate. 

To trace this process, the researchers injected ground squirrels with urea containing carbon-13, an isotope that rarely occurs naturally in the organism and is therefore easily tracked in the body. 

“We found that gut microbes extracted carbon from the urea and converted it into acetate, a critical biomolecule which the squirrels then absorbed and used during hibernation,” Regan said. “When we eliminated the microbes using antibiotics, the carbon recycling process stopped dead.” 

Previous research by the team found a similar process involving nitrogen, an essential element for protein production that is similarly cut off during hibernation. Nitrogen, which is also present in urea, is reabsorbed and reused to build proteins, helping to preserve muscle and vital functions. 

Could humans benefit? 

Regan believes these findings could have implications for humans. Urea nitrogen recycling is well-documented in ruminants such as cows and camels, whose digestive systems are specifically adapted to collaborate with microbes. 

“Humans theoretically have the same capacity,” Regan explained. “Studies from the 1990s show that we have the necessary microbes and ‘biological infrastructure,’ including cellular transporters, enzymes and metabolic pathways. But we’re far less efficient than hibernators.” 

He noted that squirrels gradually ramp up their recycling ability during hibernation, peaking just before they wake up in the spring. Their physiology therefore changes to maximize this life-sustaining process. 

A solution for space travel? 

Humans begin losing muscle mass and strength—a process known as sarcopenia—by age 30 or 40. Poor nutrition, poor protein balance, and some illnesses can accelerate this process.  

So can spaceflight. Muscles deteriorate rapidly in microgravity. Astronauts must train several hours per day to limit the damage, and recovery can still be slow. 

“Hibernators have evolved near-total resistance to muscle atrophy,” Regan said. “Understanding how they recycle nitrogen so efficiently could yield new ways to protect muscle mass in humans, whether on Earth or in space.” 

Published in journal: Proceedings of the National Academy of Sciences

Title: Host–microbiome mutualism drives urea carbon salvage and acetogenesis during hibernation

Authors: Matthew D. Regan, Edna Chiang, Michael Grahn, Marco Tonelli, Fariba M. Assadi-Porter, Garret Suen, and Hannah V. Carey

Source/Credit: Université de Montréal | Béatrice St-Cyr-Leroux

Reference Number: zoo031226_01

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