Intestinal permeability--a new target for disease prevention and therapy

Stephan C Bischoff, Giovanni Barbara, Wim Buurman, Theo Ockhuizen, Jörg-Dieter Schulzke, Matteo Serino, Herbert Tilg, Alastair Watson, Jerry M Wells, Stephan C Bischoff, Giovanni Barbara, Wim Buurman, Theo Ockhuizen, Jörg-Dieter Schulzke, Matteo Serino, Herbert Tilg, Alastair Watson, Jerry M Wells

Abstract

Data are accumulating that emphasize the important role of the intestinal barrier and intestinal permeability for health and disease. However, these terms are poorly defined, their assessment is a matter of debate, and their clinical significance is not clearly established. In the present review, current knowledge on mucosal barrier and its role in disease prevention and therapy is summarized. First, the relevant terms 'intestinal barrier' and 'intestinal permeability' are defined. Secondly, the key element of the intestinal barrier affecting permeability are described. This barrier represents a huge mucosal surface, where billions of bacteria face the largest immune system of our body. On the one hand, an intact intestinal barrier protects the human organism against invasion of microorganisms and toxins, on the other hand, this barrier must be open to absorb essential fluids and nutrients. Such opposing goals are achieved by a complex anatomical and functional structure the intestinal barrier consists of, the functional status of which is described by 'intestinal permeability'. Third, the regulation of intestinal permeability by diet and bacteria is depicted. In particular, potential barrier disruptors such as hypoperfusion of the gut, infections and toxins, but also selected over-dosed nutrients, drugs, and other lifestyle factors have to be considered. In the fourth part, the means to assess intestinal permeability are presented and critically discussed. The means vary enormously and probably assess different functional components of the barrier. The barrier assessments are further hindered by the natural variability of this functional entity depending on species and genes as well as on diet and other environmental factors. In the final part, we discuss selected diseases associated with increased intestinal permeability such as critically illness, inflammatory bowel diseases, celiac disease, food allergy, irritable bowel syndrome, and--more recently recognized--obesity and metabolic diseases. All these diseases are characterized by inflammation that might be triggered by the translocation of luminal components into the host. In summary, intestinal permeability, which is a feature of intestinal barrier function, is increasingly recognized as being of relevance for health and disease, and therefore, this topic warrants more attention.

Figures

Figure 1
Figure 1
Relation between intestinal permeability, intestinal microbiota, and mucosal immunology. For details see text.
Figure 2
Figure 2
Chemical and physical barriers in the intestine. For explanations see text.
Figure 3
Figure 3
Cell shedding leading to a temporary epithelial defect. Outwardly directed flow of fluorescein through a epithelial defect created by incomplete sealing of a gap created by cell shedding. Image obtained by confocal laser endomicroscopy of a patient with small bowel Crohn’s disease.
Figure 4
Figure 4
Intestinal barrier dysfunctions. Intestinal permeability measurements are determined by the marker molecules used for measurement, since the type of molecules that pass the intestinal barrier depends on the type of lesion.
Figure 5
Figure 5
The Ussing chamber. Upper left: Ussing chamber equipment. Upper right: Mounting a tissue specimen in a chamber for measurement. Lower panel: schematic view of an Ussing chamber setting. For details see text.
Figure 6
Figure 6
Tight junctions in the intestine. This figure is based on previously published data [115] and shows fluorescent staining of occludin in a tissue section perpendicular to the cell surface of the epithelium (A). The fluorescence intensities of 3 different uniform areas per section were plotted as a function of cell location using the peak fluorescence signal from the tight junction region to align each intensity profile (B). Administration of live L. plantarum to humans significantly increased the fluorescent staining of occludin in the tight junction (P < 0.05 for sections indicated *).
Figure 7
Figure 7
Current concepts on the pathophysiology of obesity and metabolic diseases related to the gut. For details see text.

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