Urea nitrogen recycling via gut symbionts increases in hibernators over the winter fast

Abstract

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. Here, we reveal gut microbiome-mediated urea nitrogen recycling in hibernating 13-lined ground squirrels (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. Urea nitrogen recycling is greatest after prolonged fasting in late winter, when urea transporter abundance in gut tissue and urease gene abundance in the microbiome are highest. 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. One Sentence SummaryGround squirrels and their gut symbionts benefit from urea nitrogen recycling throughout hibernation.