Xia Yi-Meng, Zhang Mei-Xuan, Ma Xiao-Yu, Tan Lu-Lu, Li Ting, Wu Jian, Li Ming-An, Zhao Wei-Jiang, Qiao Chen-Meng, Jia Xue-Bing, Shen Yan-Qin, Cui Chun
Laboratory of Neurodegenerative Diseases, Wuxi School of Medicine, Jiangnan University, Wuxi 214122, China.
MOE Medical Basic Research Innovation Center for Gut Microbiota and Chronic Diseases, Wuxi School of Medicine, Jiangnan University, Wuxi 214122, China.
Brain Sci. 2025 Apr 23;15(5):433. doi: 10.3390/brainsci15050433.
Parkinson's disease (PD) is characterized by early-onset olfactory dysfunction preceding motor symptoms, yet its mechanisms remain elusive. Based on the studies on microbiota-gut-brain axis, the microbiota-nose-brain axis might be involved in the pathogenesis of PD. However relative studies are rare.
By consecutive 14-days intranasally transplanting bacteria, we established mice models exhibiting nasal microbiota dysbiosis (NMD), including animal group received intranasal drops of fecal bacterial suspension from normal mice (NB group) and animal group received intranasal drops of fecal bacterial suspension from PD mice (PB group), with animals that only received anesthesia used as the control group. Then we analyzed the nasal microbiota composition via 16S rRNA sequencing, evaluated the olfactory and motor functions through behavioral experiments, including buried food test, open field test, pole descent test, and traction test. The neuropathology in olfactory-related and PD-related brain regions, including olfactory bulb, pyriform cortex, hippocampus, substantia nigra and striatum, was also detected by western blotting, immunofluorescence and immunohistochemical experiments using the antibodies of NeuN, TH and GFAP.
16S rRNA sequencing revealed that PB mice were primarily characterized by an increase in bacteria associated with inflammation and PD. Behavioral assessments revealed that mice with NMD demonstrated impairments in the buried food test and pole descent test, indicative of olfactory and motor dysfunction. By detecting NeuN and GFAP expression, we identified neuronal loss and astrocytes activation in olfactory-related brain regions and adjacent structures, including the olfactory bulb, pyriform cortex, hippocampus, substantia nigra and striatum of both NMD groups, which may contribute to the observed functional disorders. Notably, animals exposed to PD-derived bacteria exhibited more pronounced changes in nasal bacteria, with more severe neuropathology.
We present evidence supporting the microbiota-nose-brain axis, and the NMD-induced astrocyte activation and neurodegenerative pathology along the olfactory pathway may serve as a link between nose and brain.
帕金森病（PD）的特征是在运动症状出现之前就有早期嗅觉功能障碍，但其机制仍不清楚。基于对微生物群-肠道-脑轴的研究，微生物群-鼻-脑轴可能参与了PD的发病机制。然而，相关研究很少。
通过连续14天经鼻移植细菌，我们建立了表现出鼻腔微生物群失调（NMD）的小鼠模型，包括接受正常小鼠粪便细菌悬液滴鼻的动物组（NB组）和接受PD小鼠粪便细菌悬液滴鼻的动物组（PB组），仅接受麻醉的动物作为对照组。然后，我们通过16S rRNA测序分析鼻腔微生物群组成，通过行为实验评估嗅觉和运动功能，包括埋食试验、旷场试验、爬杆试验和牵引试验。还使用NeuN、TH和GFAP抗体，通过蛋白质免疫印迹、免疫荧光和免疫组织化学实验检测嗅觉相关和PD相关脑区的神经病理学，这些脑区包括嗅球、梨状皮质、海马、黑质和纹状体。
16S rRNA测序显示，PB组小鼠的主要特征是与炎症和PD相关的细菌增加。行为评估显示，患有NMD的小鼠在埋食试验和爬杆试验中表现出损伤，表明存在嗅觉和运动功能障碍。通过检测NeuN和GFAP表达，我们在两个NMD组的嗅觉相关脑区和相邻结构中，包括嗅球、梨状皮质、海马、黑质和纹状体，发现了神经元丢失和星形胶质细胞激活，这可能导致了观察到的功能障碍。值得注意的是，暴露于PD来源细菌的动物鼻腔细菌变化更明显，神经病理学更严重。
我们提供了支持微生物群-鼻-脑轴的证据，并且NMD诱导的星形胶质细胞激活和沿嗅觉通路的神经退行性病理可能是鼻子和大脑之间的联系。
