https://www.gastrojournal.org/article/S0016-5085(11)01076-6/pdf

Global and Deep Molecular Analysis of Microbiota Signatures in Fecal Samples From Patients With Irritable Bowel Syndrome

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.

/pdf/breaking-down-the-barriers-the-gut-microbiome-intestinal-42wtsbv3fq.pdf

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

Defects in intestinal barrier function are associated with diseases of the gastrointestinal (GI) tract. There is growing evidence that increases in intestinal permeability plays a pathogenic role in diseases, such as inflammatory bowel disease (IBD) and celiac disease, and functional bowel disorders, such as irritable bowel syndrome (IBS). This review takes a unique translational approach to discuss the physiological and pathophysiological mechanisms involved in the regulation of intestinal barrier function in IBS. The review summarizes the components of the intestinal barrier including the tight junction complex within the epithelium, and the methods used to assess gut permeability both in vitro and in vivo. Throughout the review, the authors have attempted to critically review the latest research from both experimental animal models and human studies to appraise whether intestinal barrier dysfunction is a primary cause of functional GI disorders, such as IBS.…

https://onlinelibrary.wiley.com/doi/epdf/10.1111/j.1365-2982.2012.01921.x

Intestinal barrier function in health and gastrointestinal disease

Epithelial tight junctions (TJs) are the key structures regulating paracellular trafficking of macromolecules. The TJ is multi-protein complex that forms a selective permeable seal between adjacent epithelial cells and demarcates the boundary between apical and basolateral membrane domains. Disruption of the intestinal TJ barrier, followed by permeation of luminal noxious molecules, induces a perturbation of the mucosal immune system and inflammation, which can act as a trigger for the development of intestinal and systemic diseases. Inflammatory bowel disease (IBD) patients demonstrate increased intestinal paracellular permeability. Although it remains unclear whether barrier dysfunction precedes disease or results from active inflammation, increased intestinal TJ disruption is observed in IBD patients suggest that dysregulation of TJ barrier integrity may predispose or enhance IBD progression. Therefore, therapeutic target to restore the TJ barrier integrity may provide effective therapeutic and preventive approaches against IBD. This review discusses the molecular structure and regulation of intestinal TJs and the involvement of intestinal TJs in IBD pathogenesis.

/pdf/intestinal-permeability-regulation-by-tight-junction-xww7jjkwdo.pdf

Intestinal permeability regulation by tight junction: implication on inflammatory bowel diseases.

https://www.gastrojournal.org/article/S0016-5085(07)00185-0/pdf

Immune activation in patients with irritable bowel syndrome

Abnormal Intestinal Permeability in Subgroups of Diarrhea-Predominant Irritable Bowel Syndromes

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Abnormal Intestinal Permeability in Subgroups of Diarrhea-Predominant Irritable Bowel Syndromes