Squirreling into the gut of ground squirrels


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Squirreling into the gut of ground squirrels

Have you ever wondered what enables ground squirrels to hold on to long periods of winter fasting and yet survive? Have you ever considered what might prompt these squirrels to hibernate for so long and still maintain their normal physiology up to 4 ft underground beneath their burrows? Well, some scientists have and they came up with one of many possible answers: gut microflora.

In 2022, research guided by a group of scientists at the University of Wisconsin-Madison on ground squirrels (scientific name: Ictidomys tridecemlineatus) found that the inherent microbes degrading urea in their gut play a vital role in hibernation – a strategy by which mammals maintain their body heat and energy levels throughout lengthy fasting when the food supply is really low or depleted. 

Like all gut microbiota, these ureolytic bacteria in the gut of ground squirrels affect the energy balance, torpor patterns (state of slowing metabolism lasting for a few days just before diving into hibernation), and arousal states by focusing on steadying the nitrogen balance during the seasonal variations.

They grouped the test animals into three groups: summer when the squirrels are most active, early winter that is 1 month into hibernation and fasting, and late winter during the 3-4 months of hibernation and fasting. All groups  were  treated with antibiotics to obtain  microbe free gut environments. Then, the squirrels were further  injected with urea for microbial gut activity.

They found that the ureolytic bacteria in the gut convert urea into two molecules: ammonia and carbon dioxide.  The mechanism used for this conversion is called ‘urea nitrogen salvage’, and it uses an enzyme called urease. One of the resulting products is ammonia that are then used to produce amino acids and proteins.

Alistipes is the most prevalent and detectable gut bacterial genus found in  ground squirrels. This genus is responsible for producing most urease genes that become 6 times more prevalent during winter hibernation. Source: https://microbiomology.org/microbe/alistipes/

The gut bacteria obtain their supply of urea from the bloodstream that was produced in the liver by the  process called hepatic urea synthesis. This bloodstream urea, that has not been excreted from the kidney, enters the gut lumen where the ureolytic bacteria reside. The bacteria, then, use the ammonia (product of urease activity) as a nitrogen source to produce amino acids, which are incorporated back to the host circulatory system. This is why ground squirrels display lower blood urea levels as hibernators (late winter) than during summer, when they are not hibernating.

Principle of the urea nitrogen mechanism. Source: Gavin S. Stewart and Craig P. Smith (2005)

A previous study conducted by Hannah V. Carey and her team in 2013 showed that ground squirrels demonstrate a dynamic microbiota that  tends to restructure itself  by increasing acetate and butyrate levels and declining ammonia levels during the period of hibernation. They stated that microbial taxa vary depending on seasonal changes and consequently, alter gut environment as the available substrates shift from dietary to host -derived.

For example, during summer, squirrels are found to be most active with a flourishing microflora and a high rate of ureolysis, which still continues throughout the winter. Interestingly, it is during the late winter hibernation period, that most gut bacteria express their genes for ureolytic activity in turn displaying a higher ureolytic potential in late winter. During this period lasting for 3-4 months, they observed that the levels of urea in the bloodstream, microbial urease activity and subsequent carbon dioxide levels decreased, while urea is consistently added into the squirrel’s amino acids, hence maintaining the host’s body mass and protein levels despite prolonged fasting during the hibernation.

The dynamic gut microbiota in ground squirrels during the hibernation cycle over a year. Source: Hannah V Carey et al (2013)

Thus, the nitrogen salvage mechanism employed by these ureolytic bacteria is a key factor for the ground squirrels to adapt and survive food scarcity due to seasonal changes. This immense beneficial strategy has two main advantages. First, despite the lack of dietary supply and being on the cusp of breeding season, nitrogen balance is maintained and the normal protein functioning during this late hibernation period can be advantageous for competitive reproduction. Second, starvation during hibernation also equates to a long period of water deprivation. By utilizing the urea in the bloodstream and, subsequently, diverting it from the kidneys, the ureolytic bacteria in the gut aid in conserving water in the host body system through less urine production.

This area of research is especially significant to us to overcome the effects and implications of nitrogen limited diets and sarcopenia – identified by signs of reduced muscle mass, muscle strength and physical performance, which have been a bane for many on a global scale. A good understanding of mitigating nitrogen stress (in hibernators like ground squirrels) by urea nitrogen salvage mechanism would definitely help us to strategize ways to enhance muscle preservation in humans, wouldn’t you agree?

Link to the original post: Regan, M.D. et al. 27 January 2022. Nitrogen recycling via gut symbionts increases in groun squirrels over the hibernation period. Science (375), 6579, 460-463. DOI: 10.1126/science.abh2950

Featured image:  https://eol.org/pages/1178597