Abstract
An increased intestinal permeability has been described in various gastrointestinal and non-gastrointestinal disorders. Nevertheless, the concept and definition of intestinal permeability is relatively broad and includes not only an altered paracellular route, regulated by tight junction proteins, but also the transcellular route involving membrane transporters and channels, and endocytic mechanisms. Paracellular intestinal permeability can be assessed in vivo by using different molecules (e.g., sugars, polyethylene glycols, 51Cr-EDTA) and ex vivo in Ussing chambers combining electrophysiology and probes of different molecular sizes. The latter is still the gold standard technique for assessing the epithelial barrier function, whereas in vivo techniques, including putative blood biomarkers such as intestinal fatty acid-binding protein and zonulin, are broadly used despite limitations. In the second part of the review, the current evidence of the role of impaired barrier function in the pathophysiology of selected gastrointestinal and liver diseases is discussed. Celiac disease is one of the conditions with the best evidence for impaired barrier function playing a crucial role with zonulin as its proposed regulator. Increased permeability is clearly present in inflammatory bowel disease, but the question of whether this is a primary event or a consequence of inflammation remains unsolved. The gut-liver axis with a crucial role in impaired intestinal barrier function is increasingly recognized in chronic alcoholic and metabolic liver disease. Finally, the current evidence does not support an important role for increased permeability in bile acid diarrhea.
Highlights
The concept of the “leaky gut” known as increased intestinal permeability has been described many years ago and is currently receiving increasing attention in the scientific literature and in the media because of its proposed associations with numerous conditions that do not necessarily affect the gastrointestinal (GI) tract, such as asthma, Alzheimer’s disease, diabetes among others
To better comprehend the role of an increased intestinal permeability in GI diseases, it is crucial to understand some basic concepts on how different molecules cross the intestinal epithelium and how intestinal permeability can be evaluated in humans
Overall there are four different pathways: (a) the transcellular route used by small hydrophilic and lipophilic compounds; (b) the paracellular route used by ions, water and larger hydrophilic compounds from ∼400–600 Da up to 10–20 kDa and that cannot cross transcellularly [regulated by the tight junction (TJ) proteins]; (c) transcellular active transport used by nutrients as sugars, amino acids and vitamins that require specific transporters and energy and (d) endocytosis and basolateral exocytosis via vesicles are used by larger peptides and proteins, large bacterial components or even whole bacteria [1, 2]
Summary
The concept of the “leaky gut” known as increased intestinal permeability has been described many years ago and is currently receiving increasing attention in the scientific literature and in the media because of its proposed associations with numerous conditions that do not necessarily affect the gastrointestinal (GI) tract, such as asthma, Alzheimer’s disease, diabetes among others. Overall there are four different pathways: (a) the transcellular route used by small hydrophilic and lipophilic compounds; (b) the paracellular route used by ions, water and larger hydrophilic compounds from ∼400–600 Da up to 10–20 kDa and that cannot cross transcellularly [regulated by the tight junction (TJ) proteins]; (c) transcellular active transport used by nutrients as sugars, amino acids and vitamins that require specific transporters and energy and (d) endocytosis and basolateral exocytosis via vesicles are used by larger peptides and proteins, large bacterial components or even whole bacteria [1, 2]. LPS can potentially cross the enterocyte via the different mechanisms involved in endocytosis: [1] clathrin-mediated endocytosis; [2] lipid-raft caveolae- mediated endocytosis; and [3] via the chylomicrons pathway (only in the small intestine) [19, 20] If these findings can be confirmed in disease conditions, they will strongly challenge the broadly extended concept of “leaky gut” [21]. Despite the increased LPS translocation into the blood described in numerous pathologies, it is not clear whether blood endotoxin levels are the result of LPS from the lumen or whether LPS is released by whole bacteria translocated in the lamina propria by the wall breakdown from effective host defense mechanisms and by autolysis [26]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
