Locomotor activity is an innate behavior that can be triggered by gut-motivated conditions, such as appetite and metabolic condition. Various nutrient-sensing receptors distributed in the vagal terminal in the gut are crucial for signal transduction from the gut to the brain. The levels of gut hormones are closely associated with the colonization status of the gut microbiota, suggesting a complicated interaction among gut bacteria, gut hormones, and the brain. However, the detailed mechanism underlying gut microbiota-mediated endocrine signaling in the modulation of locomotion is still unclear. Herein, we show that broad-spectrum antibiotic cocktail (ABX)-treated mice displayed hypolocomotion and elevated levels of the gut hormone glucagon-like peptide-1 (GLP-1). Blockade of the GLP-1 receptor and subdiaphragmatic vagal transmission rescued the deficient locomotor phenotype in ABX-treated mice. Activation of the GLP-1 receptor and vagal projecting brain regions led to hypolocomotion. Finally, selective antibiotic treatment dramatically increased serum GLP-1 levels and decreased locomotion. Colonizing Lactobacillus reuteri and Bacteroides thetaiotaomicron in microbiota-deficient mice suppressed GLP-1 levels and restored the hypolocomotor phenotype. Our findings identify a mechanism by which specific gut microbes mediate host motor behavior via the enteroendocrine and vagal-dependent neural pathways.

运动活动是一种先天行为，可以由肠道诱发的条件（例如食欲和代谢状况）触发。分布在肠道迷走神经末梢的各种营养感应受体对于从肠道到大脑的信号转导至关重要。肠道激素的水平与肠道微生物群的定植状态密切相关，这表明肠道细菌、肠道激素和大脑之间存在着复杂的相互作用。然而，肠道微生物介导的内分泌信号在运动调节中的详细机制仍不清楚。在此，我们发现广谱抗生素混合物 (ABX) 治疗的小鼠表现出运动减退和肠道激素胰高血糖素样肽 1 (GLP-1) 水平升高。阻断 GLP-1 受体和膈下迷走神经传导可以挽救 ABX 治疗小鼠的运动表型缺陷。GLP-1 受体和迷走神经投射大脑区域的激活导致运动减退。最后，选择性抗生素治疗显着增加血清 GLP-1 水平并降低运动能力。在微生物群缺陷的小鼠体内定植罗伊氏乳杆菌和多形拟杆菌可抑制 GLP-1 水平并恢复运动功能减退表型。我们的研究结果确定了特定肠道微生物通过肠内分泌和迷走神经依赖性神经通路介导宿主运动行为的机制。