Regan Matthew D, Chiang Edna, Grahn Michael, Tonelli Marco, Assadi-Porter Fariba M, Suen Garret, Carey Hannah V
Department of Comparative Biosciences, University of Wisconsin-Madison, Madison, WI, USA.
Département de Sciences Biologiques, Université de Montréal, Montréal, QC, Canada.
bioRxiv. 2025 Aug 19:2025.02.13.638127. doi: 10.1101/2025.02.13.638127.
Hibernation is a seasonal survival strategy employed by certain mammals that, through torpor use, reduces overall energy expenditure and permits long-term fasting. Although fasting solves the challenge of winter food scarcity, it also removes dietary carbon, a critical biomolecular building block. Here, we demonstrate a process of urea carbon salvage (UCS) in hibernating 13-lined ground squirrels, whereby urea carbon is reclaimed through gut microbial ureolysis and used in reductive acetogenesis to produce acetate, a short-chain fatty acid (SCFA) of major value to the host and its gut microbiota. We find that urea carbon incorporation into acetate is more efficient during hibernation than the summer active season, and that while both host and gut microbes oxidize acetate for energy supply throughout the year, the host's ability to absorb and oxidize acetate is highest during hibernation. Metagenomic analysis of the gut microbiome indicates that genes involved in the degradation of gut mucins, an abundant endogenous nutrient, are retained during hibernation. The hydrogen disposal associated with reductive acetogenesis from urea carbon helps facilitate this mucin degradation by providing a luminal environment that sustains fermentation, thereby generating SCFAs and other metabolites usable by both the host and its gut microbes. Our findings introduce UCS as a mechanism that enables hibernating squirrels and their gut microbes to exploit two key endogenous nutrient sources - urea and mucins - in the resource-limited hibernation season.
冬眠是某些哺乳动物采用的一种季节性生存策略，通过进入蛰伏状态，降低总体能量消耗并允许长期禁食。虽然禁食解决了冬季食物短缺的挑战，但它也去除了饮食中的碳，而碳是一种关键的生物分子组成部分。在这里，我们展示了冬眠的三线地松鼠体内的尿素碳回收（UCS）过程，即尿素碳通过肠道微生物尿素分解作用被回收，并用于还原性产乙酸过程以产生乙酸，乙酸是一种对宿主及其肠道微生物群具有重要价值的短链脂肪酸（SCFA）。我们发现，与夏季活跃季节相比，冬眠期间尿素碳掺入乙酸的效率更高，而且虽然宿主和肠道微生物全年都会氧化乙酸以供能，但宿主吸收和氧化乙酸的能力在冬眠期间最高。对肠道微生物群的宏基因组分析表明，参与肠道粘蛋白（一种丰富的内源性营养物质）降解的基因在冬眠期间得以保留。与尿素碳还原性产乙酸相关的氢气处理通过提供维持发酵的管腔环境，有助于促进这种粘蛋白降解，从而产生宿主及其肠道微生物都可用的短链脂肪酸和其他代谢产物。我们的研究结果引入了尿素碳回收这一机制，该机制使冬眠的松鼠及其肠道微生物能够在资源有限的冬眠季节利用两种关键的内源性营养源——尿素和粘蛋白。
