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Review
. 2015 Oct 14:9:392.
doi: 10.3389/fncel.2015.00392. eCollection 2015.

Breaking down the barriers: the gut microbiome, intestinal permeability and stress-related psychiatric disorders

John R Kelly  1 , Paul J Kennedy  2 , John F Cryan  3 , Timothy G Dinan  1 , Gerard Clarke  1 , Niall P Hyland  4
Affiliations
Review

Breaking down the barriers: the gut microbiome, intestinal permeability and stress-related psychiatric disorders

John R Kelly et al. Front Cell Neurosci. .

Abstract

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.

Keywords: depression; gut microbiota; gut-brain axis; intestinal barrier; probiotics; psychobiotics.

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Figures

Figure 1
Figure 1
The brain-gut-microbiota axis. Postulated signaling pathways between the gut microbiota, the intestinal barrier and the brain. A dysfunctional intestinal barrier or “leaky gut” could permit a microbiota-driven proinflammatory state with implications for neuroinflammation.
Figure 2
Figure 2
Potential neuropsychiatric consequences of a dysregulated intestinal barrier. Activation of brain-gut-microbiota Axis signaling pathways via a compromised intestinal barrier with potential effects on mood, anxiety, cognition and social interaction.
See this image and copyright information in PMC

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References

    1. Abreu M. T. (2010). Toll-like receptor signalling in the intestinal epithelium: how bacterial recognition shapes intestinal function. Nat. Rev. Immunol. 11, 215–215. 10.1038/nri2728 - DOI - PubMed
    1. Agostini S., Goubern M., Tondereau V., Salvador-Cartier C., Bezirard V., Lévèque M., et al. . (2012). A marketed fermented dairy product containing Bifidobacterium lactis CNCM I-2494 suppresses gut hypersensitivity and colonic barrier disruption induced by acute stress in rats. Neurogastroenterol. Motil. 24, 376–e172. 10.1111/j.1365-2982.2011.01865.x - DOI - PubMed
    1. Ait-Belgnaoui A., Bradesi S., Fioramonti J., Theodorou V., Bueno L. (2005). Acute stress-induced hypersensitivity to colonic distension depends upon increase in paracellular permeability: role of myosin light chain kinase. Pain 113, 141–147. 10.1016/j.pain.2004.10.002 - DOI - PubMed
    1. Ait-Belgnaoui A., Colom A., Braniste V., Ramalho L., Marrot A., Cartier C., et al. . (2014). Probiotic gut effect prevents the chronic psychological stress-induced brain activity abnormality in mice. Neurogastroenterol. Motil. 26, 510–520. 10.1111/nmo.12295 - DOI - PubMed
    1. Ait-Belgnaoui A., Durand H., Cartier C., Chaumaz G., Eutamene H., Ferrier L., et al. . (2012). Prevention of gut leakiness by a probiotic treatment leads to attenuated HPA response to an acute psychological stress in rats. Psychoneuroendocrinology 37, 1885–1895. 10.1016/j.psyneuen.2012.03.024 - DOI - PubMed