PDF(Pubmed)
Abstract：
Gut microbiota is responsible for essential functions in human health. Several communication axes between gut microbiota and other organs via neural, endocrine, and immune pathways have been described, and perturbation of gut microbiota composition has been implicated in the onset and progression of an emerging number of diseases. Here, we analyzed peripheral nerves, dorsal root ganglia (DRG), and skeletal muscles of neonatal and young adult mice with the following gut microbiota status: a) germ-free (GF), b) gnotobiotic, selectively colonized with 12 specific gut bacterial strains (Oligo-Mouse-Microbiota, OMM12), or c) natural complex gut microbiota (CGM). Stereological and morphometric analyses revealed that the absence of gut microbiota impairs the development of somatic median nerves, resulting in smaller diameter and hypermyelinated axons, as well as in smaller unmyelinated fibers. Accordingly, DRG and sciatic nerve transcriptomic analyses highlighted a panel of differentially expressed developmental and myelination genes. Interestingly, the type III isoform of Neuregulin1 (NRG1), known to be a neuronal signal essential for Schwann cell myelination, was overexpressed in young adult GF mice, with consequent overexpression of the transcription factor Early Growth Response 2 (Egr2), a fundamental gene expressed by Schwann cells at the onset of myelination. Finally, GF status resulted in histologically atrophic skeletal muscles, impaired formation of neuromuscular junctions, and deregulated expression of related genes. In conclusion, we demonstrate for the first time a gut microbiota regulatory impact on proper development of the somatic peripheral nervous system and its functional connection to skeletal muscles, thus suggesting the existence of a novel \'Gut Microbiota-Peripheral Nervous System-axis.\'
摘要：
肠道微生物群负责人类健康的基本功能。肠道微生物群和其他器官之间通过神经的几个交流轴，内分泌，和免疫途径已经被描述，和肠道微生物群组成的扰动与许多新出现的疾病的发病和进展有关。这里,我们分析了周围神经,背根神经节（DRG），和具有以下肠道微生物群状态的新生和年轻成年小鼠的骨骼肌：a）无菌（GF），b)侏儒，选择性定植12种特定的肠道细菌菌株(Oligo-Mouse-Microbiota，OMM12),或c)天然复杂肠道微生物群(CGM)。体视学和形态学分析显示，肠道微生物群的缺乏会损害体细胞正中神经的发育，导致更小的直径和髓鞘过多的轴突，以及较小的无髓鞘纤维。因此，DRG和坐骨神经转录组学分析强调了一组差异表达的发育和髓鞘形成基因。有趣的是,神经调节蛋白1(NRG1)的III型同工型，已知是雪旺氏细胞髓鞘形成所必需的神经元信号，在年轻的成年GF小鼠中过表达，随后过度表达转录因子早期生长反应2（Egr2），一种由施万细胞在髓鞘形成开始时表达的基本基因。最后,GF状态导致组织学萎缩的骨骼肌，神经肌肉接头形成受损，和相关基因的表达失调。总之,我们首次证明了肠道微生物群对躯体周围神经系统的正常发育及其与骨骼肌的功能连接的调节作用，因此表明存在一种新的肠道微生物群-周围神经系统轴。\'
