Nature:肠道菌群如何作用于结肠神经,调控肠道蠕动?
创作:mildbreeze 审核:mildbreeze 02月06日
  • 小鼠结肠(菌群最多的肠段)的神经网络有独特的基因表达谱,受遗传和菌群定植的共同调控;
  • 不同肠段肠神经元的芳香烃受体(AHR)表达水平与菌群载量一致,结肠神经的AHR表达最高,其AHR信号活化可诱导Kcnj12(调控神经元兴奋性)等效应基因的表达;
  • 敲除神经Ahr基因,或过表达其负反馈调控因子CYP1A1,可导致小鼠结肠蠕动减少,该表型与清除菌群的小鼠类似;
  • 在抗生素处理的小鼠的肠神经中表达Ahr,可部分恢复其肠道运动缺陷。
主编推荐语
mildbreeze
肠道蠕动对消化健康和抵御肠道致病菌入侵有重要意义,肠腔内环境(比如饮食和菌群因素)可作用于肠神经,从而调控肠道蠕动,比如清除菌群的小鼠呈现肠神经元兴奋性降低、肠道运输时间变长等表型,但背后的分子机制尚不明晰。Nature上线的一项最新研究表明,肠神经回路中的芳香烃受体(AHR)信号,是连接菌群等肠腔环境因素与肠神经功能的枢纽,在肠道运动调控上有重要作用。用药物或饮食干预来调节控制肠道蠕动的肠神经元的AHR活性,或能改善肠道蠕动障碍相关的胃肠疾病。
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Nature [IF:43.07]

Neuronal programming by microbiota regulates intestinal physiology

菌群的神经元编程调控肠道生理

10.1038/s41586-020-1975-8

02-05, Article

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Abstract:收起
Neural control of the function of visceral organs is essential for homeostasis and health. Intestinal peristalsis is critical for digestive physiology and host defence, and is often dysregulated in gastrointestinal disorders1. Luminal factors, such as diet and microbiota, regulate neurogenic programs of gut motility2,3,4,5, but the underlying molecular mechanisms remain unclear. Here we show that the transcription factor aryl hydrocarbon receptor (AHR) functions as a biosensor in intestinal neural circuits, linking their functional output to the microbial environment of the gut lumen. Using nuclear RNA sequencing of mouse enteric neurons that represent distinct intestinal segments and microbiota states, we demonstrate that the intrinsic neural networks of the colon exhibit unique transcriptional profiles that are controlled by the combined effects of host genetic programs and microbial colonization. Microbiota-induced expression of AHR in neurons of the distal gastrointestinal tract enables these neurons to respond to the luminal environment and to induce expression of neuron-specific effector mechanisms. Neuron-specific deletion of Ahr, or constitutive overexpression of its negative feedback regulator CYP1A1, results in reduced peristaltic activity of the colon, similar to that observed in microbiota-depleted mice. Finally, expression of Ahr in the enteric neurons of mice treated with antibiotics partially restores intestinal motility. Together, our experiments identify AHR signalling in enteric neurons as a regulatory node that integrates the luminal environment with the physiological output of intestinal neural circuits to maintain gut homeostasis and health.

First Authors:
Yuuki Obata

Correspondence Authors:
Yuuki Obata,Vassilis Pachnis

All Authors:
Yuuki Obata,Álvaro Castaño,Stefan Boeing,Ana Carina Bon-Frauches,Candice Fung,Todd Fallesen,M Gomez de Aguero,Bahtiyar Yilmaz,Rita Lopes,Almaz Huseynova,Stuart Horswell,Muralidhara Rao Maradana,Werend Boesmans,Pieter Vanden Berghe,Andrew J Murray,Brigitta Stockinger,Andrew J Macpherson,Vassilis Pachnis

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