title: Breaking down the barriers: the gut microbiome, intestinal permeability and stress-related psychiatric disorders.
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.
authors.affiliation: Laboratory of Neurogastroenterology, APC Microbiome Institute, University College Cork Cork, Ireland ; Department of Psychiatry and Neurobehavioural Science, University College Cork Cork, Ireland.
authors.forename: John R
authors.initials: JR
authors.lastname: Kelly
authors.affiliation: Laboratory of Neurogastroenterology, APC Microbiome Institute, University College Cork Cork, Ireland.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Kennedy
authors.affiliation: Laboratory of Neurogastroenterology, APC Microbiome Institute, University College Cork Cork, Ireland ; Department of Anatomy and Neuroscience, University College Cork Cork, Ireland.
authors.forename: John F
authors.initials: JF
authors.lastname: Cryan
authors.affiliation: Laboratory of Neurogastroenterology, APC Microbiome Institute, University College Cork Cork, Ireland ; Department of Psychiatry and Neurobehavioural Science, University College Cork Cork, Ireland.
authors.forename: Timothy G
authors.initials: TG
authors.lastname: Dinan
authors.affiliation: Laboratory of Neurogastroenterology, APC Microbiome Institute, University College Cork Cork, Ireland ; Department of Psychiatry and Neurobehavioural Science, University College Cork Cork, Ireland.
authors.forename: Gerard
authors.initials: G
authors.lastname: Clarke
authors.affiliation: Laboratory of Neurogastroenterology, APC Microbiome Institute, University College Cork Cork, Ireland ; Department of Pharmacology and Therapeutics, University College Cork Cork, Ireland.
authors.forename: Niall P
authors.initials: NP
authors.lastname: Hyland
keywords: depression; gut microbiota; gut-brain axis; intestinal barrier; probiotics; psychobiotics