小柯机器人

肠道菌群调节肠道平衡的新机制
2020-02-12 13:11

英国弗朗西斯•克里克研究所Vassilis Pachnis和Yuuki Obata合作的最新研究发现通过微生物群进行神经元编程可调节肠道生理。该项研究成果在线发表在2020年2月5日出版的《自然》上。

研究人员发现转录因子芳烃受体(AHR)在肠道神经回路中充当生物传感器,并将其功能与肠腔微生物环境联系起来。使用代表不同肠段和微生物群状态的小鼠肠神经核RNA测序,研究人员发现结肠内在神经网络表现出独特的转录谱,该转录谱受宿主基因和微生物定殖的综合作用调控。在远端胃肠道神经元中微生物诱导的AHR表达使这些神经元能够响应腔环境并诱导神经元特异性效应器的表达。神经元Ahr的特异性缺失或它的负反馈调节剂CYP1A1的组成型过表达会导致结肠蠕动活性降低,这与在微生物群缺失小鼠中观察到的现象相似。最后,在用抗生素处理过的小鼠肠神经元中表达Ahr可部分恢复肠蠕动。总之,该研究认为AHR信号是肠神经元中的一个调节节点,该信号将腔环境与肠道神经回路的生理输出相结合,以维持肠道稳态和健康。

据了解,神经对器官功能的调控对于体内平衡和健康至关重要。肠蠕动对于消化和宿主防御功能至关重要,并且常常在胃肠道疾病中失调。饮食和微生物群等Luminal因子是调节肠道运动的神经源程序,但仍不清楚其潜在的分子机制。

附:英文原文

Title: Neuronal programming by microbiota regulates intestinal physiology

Author: Yuuki Obata, lvaro Castao, Stefan Boeing, Ana Carina Bon-Frauches, Candice Fung, Todd Fallesen, Mercedes Gomez de Agero, 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

Issue&Volume: 2020-02-05

Abstract: 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.

DOI: 10.1038/s41586-020-1975-8

Source: https://www.nature.com/articles/s41586-020-1975-8

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:69.504
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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