# Increased urea nitrogen salvaging by a remodeled gut microbiota helps nonhibernating pikas maintain protein homeostasis during winter

## TL;DR

Non-hibernating pikas adapt to winter protein scarcity by remodeling their gut microbiota to recycle nitrogen more efficiently.

## Contribution

The study reveals microbiota-driven urea nitrogen recycling as a key adaptive strategy in winter-active herbivores.

## Key findings

- Winter protein restriction downregulates hepatic urea-cycle metabolism in plateau pikas.
- Increased abundance of ureolytic bacteria like Alistipes enhances nitrogen recycling and protein homeostasis.
- Fecal microbiota transplantation from yaks boosts ureolytic capacity in pikas.

## Abstract

Nitrogen balance is a major challenge for herbivores when consuming a low-nitrogen diet. Gut microbiota-mediated urea nitrogen recycling facilitates protein homeostasis during times of nitrogen deficiency, yet its relevance to wild nonhibernating small mammals remains unclear. Here, through a combination of isotope tracing, metagenomics, targeted short-chain fatty acid analysis, and fecal microbiota transplantation, we investigated the effects of protein restriction in winter on urea nitrogen recycling in plateau pikas (Ochotona curzoniae) of the Qinghai–Tibetan Plateau. Hepatic urea-cycle metabolism was downregulated during winter protein restriction, accompanied by increases in beneficial bacteria with ureolytic capacity (such as the genus Alistipes), gut urease activity, and urea transporters, and acetate production, with a consequent increase in nitrogen reincorporation into the pika’s protein pool. Critically, supplementing a low-protein diet with yak fecal microbiota enhanced the ureolytic capacity by increasing Alistipes abundance, revealing a critical mechanism whereby interspecies horizontal microbial transfer between sympatric species enhances host protein homeostasis. Our results reveal a functional role for the gut microbiota in urea nitrogen recycling to maintain protein balance in winter-active herbivorous small mammals and contribute to our understanding of species coexistence and mammalian adaptation to high-altitude environments. Our findings establish that microbiota-driven urea nitrogen recycling is a key adaptive strategy for protein homeostasis in winter-active herbivores. This work provides new insights into the mechanisms of mammalian adaptation to high-altitude environments and the dynamics of interspecies coexistence.

Winter-active herbivores often experience difficulty obtaining sufficient nitrogen during winter months, when dietary protein becomes scarce. This study reveals that winter protein restriction drives gut microbiome remodeling in the non-hibernating plateau pika, increasing microbiome nitrogen recycling capacity and helping maintain host protein balance.