<b>High-tannin food enhances spatial memory and scatter-hoarding via the microbiota-gut-brain axis of rodents</b>

The mutually beneficial coevolutionary relationships between rodents and plant seeds have been a hot topic of research in plant-animal relationships. Seed tannins are important secondary metabolites of plants that regulate food-hoarding behavior of rodents; however, the underlying molecular mechanisms are not yet clear. In this study, we investigate whether and how seed tannins improve spatial memory and regulate the hoarding behavior of <i>Tamias sibiricus</i> by altering their gut microbiota. We show that acorn tannins not only improve spatial memory but enhance scatter-hoarding of <i>T. sibiricus</i>. Changes in the composition and function of the gut microbiota in response to tannins from acorns are closely related to these improvement and enhancement. Metabonomic analyses evidence the role of gut isovaleric acid andisobutyric acid as well as serum L-tryptophan in mediating spatial memory of <i>T. sibiricus</i> via the gut microbiota. The hippocampus proteome provides further evidence for the microbiota-gut-brain axis in regulating spatial memory and scatter-hoarding of animals. Our study is likely the first to report that plant secondary metabolites improve hippocampal function and spatial memory, and ultimately modulate food-hoarding behavior via the microbiota-gut-brain axis. Our study provides a new direction for the study of the mutualistic interaction between plant secondary metabolites and food-hoarding rodents.啮齿动物与植物种子之间的互利共进化关系，一直是动植物互作领域的研究热点。种子单宁是植物重要的次生代谢产物，可调控啮齿动物的贮食行为，但其背后的分子机制尚未阐明。本研究旨在探究种子单宁是否以及如何通过改变西伯利亚花鼠（Tamias sibiricus）的肠道菌群，来改善其空间记忆并调控贮食行为。研究结果表明，橡子单宁不仅能够提升西伯利亚花鼠的空间记忆能力，还能增强其分散贮食行为。肠道菌群在响应橡子单宁时发生的组成与功能变化，与上述能力提升和行为增强密切相关。代谢组学分析证实，肠道异戊酸、异丁酸与血清L-色氨酸可通过肠道菌群介导西伯利亚花鼠的空间记忆。海马体蛋白质组学分析进一步证实，菌群-肠-脑轴参与调控动物的空间记忆与分散贮食行为。本研究可能是首次报道植物次生代谢产物可通过菌群-肠-脑轴改善海马体功能与空间记忆，最终调控动物的贮食行为。本研究为植物次生代谢产物与贮食啮齿动物之间的互利互作研究提供了全新方向。