小柯机器人

微生物群通过肠脑回路调节交感神经元
2020-07-09 15:57

美国洛克菲勒大学Daniel Mucida和Paul A. Muller研究组合作取得最新进展。他们发现微生物群可通过肠脑回路调节交感神经元。该研究于2020年7月8日发表于《自然》。

他们通过将生物小鼠模型与转录组学、电路追踪方法和功能操作相结合,来表征微生物群对肠道相关神经元的影响。他们发现肠道微生物组调节肠道外源性交感神经元,微生物群清清除导致神经元转录因子cFos的表达增加,并且用产生短链脂肪酸的细菌感染无菌小鼠,其定植抑制了肠道交感神经节中的cFos表达。

他们利用化学遗传学操作、翻译图谱和顺行性跟踪确定了远端肠投射迷走神经元亚群,其定位在微生物群介导的肠道交感神经元模块中,并具有传入作用。在微生物清除过程中,肠壁逆行多突触神经元示踪可确定激活的脑干感觉神经核,以及传出的交感性运动前谷氨酸能神经元,它们调节胃肠道运输。这些结果揭示了通过肠道-大脑回路对肠道外源性交感激活的微生物群依赖性控制。

据了解,肠道和大脑之间的连接能够监视肠道组织及其微生物和饮食含量,调节生理肠道功能,例如营养吸收和运动性,以及通过脑线喂养的行为。因此,有可能存在检测肠道微生物并将其传递到中枢神经系统区域的回路,这些区域进而调节肠道生理状况。

附:英文原文

Title: Microbiota modulate sympathetic neurons via a gut–brain circuit

Author: Paul A. Muller, Marc Schneeberger, Fanny Matheis, Putianqi Wang, Zachary Kerner, Anoj Ilanges, Kyle Pellegrino, Josefina del Mrmol, Tiago B. R. Castro, Munehiro Furuichi, Matthew Perkins, Wenfei Han, Arka Rao, Amanda J. Picard, Justin R. Cross, Kenya Honda, Ivan de Araujo, Daniel Mucida

Issue&Volume: 2020-07-08

Abstract: Connections between the gut and brain monitor the intestinal tissue and its microbial and dietary content1, regulating both physiological intestinal functions such as nutrient absorption and motility2,3, and brain-wired feeding behaviour2. 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 physiology4. 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.

DOI: 10.1038/s41586-020-2474-7

Source: https://www.nature.com/articles/s41586-020-2474-7

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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