Breaking down the barriers: the gut microbiome, intestinal permeability and stress-related psychiatric disorders.
Breaking down the barriers: the gut microbiome, intestinal permeability and stress-related psychiatric disorders.
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DOI：
10.3389/fncel.2015.00392
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发表时间：
2015
影响因子：
5.3
通讯作者：
Hyland NP
中科院分区：
文献类型：
--
作者：
Kelly JR;Kennedy PJ;Cryan JF;Dinan TG;Clarke G;Hyland NP
肠道微生物群和中枢神经系统（CNS）之间的联系被认为是神经科学范式的转变，不仅对理解与压力相关的精神疾病的病理生理学，而且对其治疗也有可能产生影响。因此，肠道微生物组及其对宿主屏障功能的影响被定位为脑肠轴内的关键节点。越来越多的临床前证据广泛表明，肠道微生物群可以通过脑-肠-微生物群轴的免疫、内分泌和神经通路调节大脑的发育、功能和行为。解释这些特定相互作用的详细机制见解目前尚不发达。然而，“漏肠”可能促进微生物群和这些关键信号通路之间的交流的概念已经得到了关注。肠道通透性缺陷可能是抑郁症等疾病中观察到的慢性低度炎症的基础，肠道微生物组在调节肠道通透性方面起着关键作用。在这篇综述中，我们将讨论肠道微生物群在维持肠道屏障功能方面可能发挥的作用，以及当它被破坏时对中枢神经系统的影响。我们将利用临床和临床前证据来支持这一概念，以及肠道微生物群的关键特征，这些特征是正常肠道屏障功能所必需的。
The emerging links between our gut microbiome and the central nervous system (CNS) are regarded as a paradigm shift in neuroscience with possible implications for not only understanding the pathophysiology of stress-related psychiatric disorders, but also their treatment. Thus the gut microbiome and its influence on host barrier function is positioned to be a critical node within the brain-gut axis. Mounting preclinical evidence broadly suggests that the gut microbiota can modulate brain development, function and behavior by immune, endocrine and neural pathways of the brain-gut-microbiota axis. Detailed mechanistic insights explaining these specific interactions are currently underdeveloped. However, the concept that a “leaky gut” may facilitate communication between the microbiota and these key signaling pathways has gained traction. Deficits in intestinal permeability may underpin the chronic low-grade inflammation observed in disorders such as depression and the gut microbiome plays a critical role in regulating intestinal permeability. In this review we will discuss the possible role played by the gut microbiota in maintaining intestinal barrier function and the CNS consequences when it becomes disrupted. We will draw on both clinical and preclinical evidence to support this concept as well as the key features of the gut microbiota which are necessary for normal intestinal barrier function.