Connections between the gut and brain monitor the intestinal tissue and its microbial and dietary content 1 , regulating both physiological intestinal functions such as nutrient absorption and motility 2 , 3 , and brain-wired feeding behaviour 2 . It is therefore plausible that circuits exist to detect gut microorganisms and relay this information to areas of the central nervous system that, in turn, regulate gut physiology 4 . Here we characterize the influence of the microbiota on enteric-associated neurons by combining gnotobiotic mouse models with transcriptomics, circuit-tracing methods and functional manipulations. We find that the gut microbiome modulates gut-extrinsic sympathetic neurons: microbiota depletion leads to increased expression of the neuronal transcription factor cFos, and colonization of germ-free mice with bacteria that produce short-chain fatty acids suppresses cFos expression in the gut sympathetic ganglia. Chemogenetic manipulations, translational profiling and anterograde tracing identify a subset of distal intestine-projecting vagal neurons that are positioned to have an afferent role in microbiota-mediated modulation of gut sympathetic neurons. Retrograde polysynaptic neuronal tracing from the intestinal wall identifies brainstem sensory nuclei that are activated during microbial depletion, as well as efferent sympathetic premotor glutamatergic neurons that regulate gastrointestinal transit. These results reveal microbiota-dependent control of gut-extrinsic sympathetic activation through a gut–brain circuit. A combination of gnotobiotic mouse models, transcriptomics, circuit tracing and chemogenetic manipulations identifies neuronal circuits that integrate microbial signals in the gut with regulation of the sympathetic nervous system.

中文翻译：

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微生物群通过肠脑回路调节交感神经元

肠道和大脑之间的连接监测肠道组织及其微生物和膳食含量 1，调节肠道生理功能，如营养吸收和运动 2、3 和脑线喂养行为 2。因此，存在检测肠道微生物并将这些信息传递到中枢神经系统区域的电路是合理的，这些区域反过来又调节肠道生理 4。在这里，我们通过将不生菌小鼠模型与转录组学、电路追踪方法和功能操作相结合来描述微生物群对肠道相关神经元的影响。我们发现肠道微生物组调节肠道外交感神经元：微生物群耗竭导致神经元转录因子 cFos 的表达增加，用产生短链脂肪酸的细菌定殖无菌小鼠会抑制肠道交感神经节中的 cFos 表达。化学遗传学操作、平移分析和顺行追踪确定了远端肠道投射迷走神经元的一个子集，这些神经元被定位在微生物群介导的肠道交感神经元调节中具有传入作用。来自肠壁的逆行多突触神经元追踪识别出在微生物耗竭期间被激活的脑干感觉核，以及调节胃肠转运的传出交感神经运动前谷氨酸能神经元。这些结果揭示了肠道外交感神经激活通过肠道-大脑回路依赖于微生物群的控制。已知生物小鼠模型、转录组学、