Nature：肠道菌产生的神经递质，调节宿主线虫的感官行为
- ①定植于线虫肠道的普罗威登斯菌，能通过其表达的芳香酸脱羧酶生成神经递质酪胺；
- ②细菌产生的酪胺能弥补线虫对自身酪胺生物合成的需求，并影响线虫的感官决定，减少其对辛醇的规避；
- ③细菌产生的酪胺经线虫的酪胺β-羟化酶转化为章鱼胺，后者作用于ASH伤害感受性神经元上的章鱼胺受体OCTR-1，来调节线虫的厌恶嗅觉反应；
- ④定植了普罗威登斯菌的线虫在食物选择时呈现对这类细菌的偏好，这种偏好性依赖于细菌产生的酪胺和线虫的章鱼胺信号。
主编推荐语
肠道菌群可产生多样化的代谢产物，有些具有神经调控作用。《Nature》发表的一项最新研究，以线虫为模型，报道了一种菌群-肠-脑轴调控机制。该研究发现，一种由特定肠道共生细菌产生的神经调节物质，能模仿同源宿主分子的功能，从而操纵宿主的感官决定，影响线虫的食物偏好，促进双方共生。
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A neurotransmitter produced by gut bacteria modulates host sensory behaviour
肠道细菌产生的一种神经递质，调节宿主感官行为
10.1038/s41586-020-2395-5
2020-06-17, Article
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Animals coexist in commensal, pathogenic or mutualistic relationships with complex communities of diverse organisms, including microorganisms1. Some bacteria produce bioactive neurotransmitters that have previously been proposed to modulate nervous system activity and behaviours of their hosts. However, the mechanistic basis of this microbiota–brain signalling and its physiological relevance are largely unknown. Here we show that in Caenorhabditis elegans, the neuromodulator tyramine produced by commensal Providencia bacteria, which colonize the gut, bypasses the requirement for host tyramine biosynthesis and manipulates a host sensory decision. Bacterially produced tyramine is probably converted to octopamine by the host tyramine β-hydroxylase enzyme. Octopamine, in turn, targets the OCTR-1 octopamine receptor on ASH nociceptive neurons to modulate an aversive olfactory response. We identify the genes that are required for tyramine biosynthesis in Providencia, and show that these genes are necessary for the modulation of host behaviour. We further find that C. elegans colonized by Providencia preferentially select these bacteria in food choice assays, and that this selection bias requires bacterially produced tyramine and host octopamine signalling. Our results demonstrate that a neurotransmitter produced by gut bacteria mimics the functions of the cognate host molecule to override host control of a sensory decision, and thereby promotes fitness of both the host and the microorganism.
First Authors:
Michael P O Donnell
Correspondence Authors:
Michael P O Donnell,Piali Sengupta
All Authors:
Michael P O Donnell,Bennett W Fox,Pin-Hao Chao,Frank C Schroeder,Piali Sengupta
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