Gut’s role in hibernation for animals may unlock keys to survival for astronauts on long missions

Hibernating animals may hold the answers for treating humans with muscle-wasting disorders and astronauts on lengthy missions. According to new research, gut microbes play a key role in the hibernation process, an important finding for the future of space travel in particular.

With the need to get through long winters without food intake, animals in hibernation, such as the 13-lined ground squirrel, can slow their metabolism as much as 99 percent. They still need vital nutrients, however, especially proteins, to protect their bodies from losing muscle while they hibernate. Researchers at the University of Wisconsin–Madison report that hibernating ground squirrels are assisted by microbes in their gastrointestinal tract.

“The longer an animal doesn’t exercise, bones and muscles lose mass and function,” states Hannah Carey, professor emeritus, UW-Madison School of Veterinary Medicine, and co-author of the study, in a statement. “Without any dietary protein coming in, hibernators need another way to get what their muscles need.”

Thirteen-lined ground squirrels curled up for seasonal hibernation can slow their metabolic rates to as little as 1 percent of their waking activity. (Photo courtesy Rob Streiffer)

In all animals, including humans, nitrogen is an essential nutrient for the synthesis of amino acids and proteins. Most of the nitrogen accumulates in the body as urea, which is excreted in urine. Research has demonstrated that some urea is also moved into a hibernating squirrel’s digestive tract, where it is broken down by intestinal microbes. The microbes also require nitrogen. The research team speculated that some of the nitrogen from urea in the gut, once it was broken down by microbes, is incorporated into the squirrels’ bodies.

The researchers mixed urea with isotopes of nitrogen and carbon which could be traced inside the body. The altered urea was injected into the squirrels’ bloodstreams at different times in the seasonal cycles of the animals. These were the active summer days, early in hibernation, and in late winter. A sub-group of the squirrels were also treated with antibiotics, which destroyed most of the microbes usually found in the gastrointestinal tract. The researchers predicted that some of the isotope-marked nitrogen would be released by the microbes as they degraded the urea. 

“We followed that (labeled) nitrogen to the livers (of the squirrels), primarily – where it is used to make proteins – and some to muscles,” says the study’s co-investigator Fariba Assadi-Porter, a UW-Madison biochemist emeritus. “We believe we’re seeing the isotope-labeled nitrogen molecules go from the host (squirrels) to the microbiome, then converted to usable molecules by the microbes before coming back to the host (for incorporation into essential proteins), essentially being “recycled” in the hibernating animal.”

The researchers noted two features that support this microbe pathway. The squirrels,  with far fewer gut microbes after receiving antibiotics, had far less uptake of the nitrogen into liver and muscle. They found, also, that during hibernation  the squirrels’ genes changed to manufacture urease, essential for the breakdown of urea in the animals’ bodies. It served to help meet their protein needs during hibernation.

Understanding this survival mechanism during hibernation could help people on low-nitrogen diets or with muscle-wasting diseases. It would also enable lengthy voyages in space with fewer supplies, such as oxygen, food, and water. Less waste and carbon dioxide would be produced. Matthew Regan, co-author of the study and former UW-Madison post-doctoral researcher, says, “This process could theoretically reduce rates of muscle loss in space.”

The study was published in the journal Science.

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