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Microbiota-gut-brain axis in health and disease: Is NLRP3 inflammasome at the crossroads of microbiota-gut-brain communications?
Progress in Neurobiology ( IF 6.7 ) Pub Date : 2020-05-28 , DOI: 10.1016/j.pneurobio.2020.101806
Carolina Pellegrini 1 , Luca Antonioli 2 , Vincenzo Calderone 1 , Rocchina Colucci 3 , Matteo Fornai 2 , Corrado Blandizzi 2
Affiliation  

Growing evidence highlights the relevance of microbiota-gut-brain axis in the maintenance of brain homeostasis as well as in the pathophysiology of major neurological and psychiatric disorders, including Parkinson’s disease (PD), Alzheimer’s disease (AD), multiple sclerosis (MS), autism spectrum disorder (ASD) and major depressive disorder (MDD). In particular, changes in gut microbiota can promote enteric and peripheral neurogenic/inflammatory responses, which, in turn, could contribute to neuroinflammation and neurodegeneration in the central nervous system (CNS). Of note, the nucleotide-binding oligomerization domain leucine rich repeat and pyrin domain-containing protein 3 (NLRP3) inflammasome acts as a key player in both coordinating the host physiology and shaping the peripheral and central immune/inflammatory responses in CNS diseases. In this context, there is pioneering evidence supporting the existence of a microbiota-gut-inflammasome-brain axis, in which enteric bacteria modulate, via NLRP3 signaling, inflammatory pathways that, in turn, contribute to influence brain homeostasis.

The present review provides an overview of current knowledge on the role of microbiota-gut-inflammasome-brain axis in the major CNS diseases, including PD, AD, MS, ASD and MDD. In particular, though no direct and causal correlation among altered gut microbiota, NLRP3 activation and brain pathology has been demonstrated and in-depth studies are needed in this setting, our purpose was to pave the way to a novel and pioneering perspective on the pathophysiology of CNS disorders. Our intent was also to highlight and discuss whether alterations of microbiota-gut-inflammasome-brain axis support a holistic view of the pathophysiology of CNS diseases, even though each disorder displays a different clinical picture.



中文翻译:

健康和疾病中的菌群-肠脑轴:NLRP3炎性体是否在菌群-肠脑交流的十字路口?

越来越多的证据突显了微生物群-肠脑轴在维持脑稳态以及主要神经和精神疾病(包括帕金森氏病(PD),阿尔茨海默氏病(AD),多发性硬化症(MS))的病理生理中的相关性,自闭症谱系障碍(ASD)和重度抑郁症(MDD)。特别地,肠道微生物群的变化可以促进肠和外周神经原性/炎症反应,进而可以促进中枢神经系统(CNS)的神经炎症和神经变性。值得注意的是,核苷酸结合低聚结构域富含亮氨酸的重复序列和含吡喃结构域的蛋白3(NLRP3)炎性小体在协调宿主生理以及塑造CNS疾病的外周和中枢免疫/炎症反应中起着关键作用。

本综述提供了有关微生物群肠道-炎症小体-脑轴在主要中枢神经系统疾病(包括PD,AD,MS,ASD和MDD)中作用的当前知识的概述。尤其是,尽管没有证明肠道微生物群改变,NLRP3激活和脑病理学之间存在直接和因果关系,并且在这种情况下还需要深入研究,但我们的目的是为开创肠胃病理生理学开辟新思路。中枢神经系统疾病。我们的目的还在于强调和讨论微生物群-肠道-炎性体-脑轴的改变是否支持中枢神经系统疾病病理生理的整体观点,即使每种疾病表现出不同的临床表现。

更新日期:2020-05-28
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