微生物群通過腸腦迴路調節交感神經元

微生物群通過腸腦迴路調節交感神經元

作者：

小柯機器人

發布時間：2020/7/9 15:57:15

美國洛克菲勒大學Daniel Mucida和Paul A. Muller研究組合作取得最新進展。他們發現微生物群可通過腸腦迴路調節交感神經元。該研究於2020年7月8日發表於《自然》。

他們通過將生物小鼠模型與轉錄組學、電路追蹤方法和功能操作相結合，來表徵微生物群對腸道相關神經元的影響。他們發現腸道微生物組調節腸道外源性交感神經元，微生物群清清除導致神經元轉錄因子cFos的表達增加，並且用產生短鏈脂肪酸的細菌感染無菌小鼠，其定植抑制了腸道交感神經節中的cFos表達。

他們利用化學遺傳學操作、翻譯圖譜和順行性跟蹤確定了遠端腸投射迷走神經元亞群，其定位在微生物群介導的腸道交感神經元模塊中，並具有傳入作用。在微生物清除過程中，腸壁逆行多突觸神經元示蹤可確定激活的腦幹感覺神經核，以及傳出的交感性運動前穀氨酸能神經元，它們調節胃腸道運輸。這些結果揭示了通過腸道-大腦迴路對腸道外源性交感激活的微生物群依賴性控制。

據了解，腸道和大腦之間的連接能夠監視腸道組織及其微生物和飲食含量，調節生理腸道功能，例如營養吸收和運動性，以及通過腦線餵養的行為。因此，有可能存在檢測腸道微生物並將其傳遞到中樞神經系統區域的迴路，這些區域進而調節腸道生理狀況。

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