Gut metagenomes from active and hibernating 13-lined ground squirrels treated with 13C,15N-labeled urea

Hibernation is a mammalian strategy that uses metabolic plasticity to reduce energy demands and enable long-term fasting. Fasting mitigates winter food scarcity but eliminates dietary nitrogen, jeopardizing body protein balance. We reveal gut microbiome-mediated urea nitrogen recycling in the gut microbiome of hibernating 13-lined ground squirrels (Ictidomys tridecemlineatus, TLGS). Ureolytic gut microbes incorporate urea nitrogen into organic compounds that are absorbed by the host, with the nitrogen reincorporated into the TLGS protein pool. These results reveal a functional role for the gut microbiome in hibernation and suggest mechanisms by which urea nitrogen recycling contributes to protein balance in other monogastric animals, including humans.