295 Introduction In Crohn’s disease (CD), a disturbed balance between the gut mucosal immune system and intestinal microbiota is intimately associated with diminished functioning of the intestinal barrier. This barrier is instrumental in the protection against adhesion and infiltration of intraluminal antigens into the underlying lamina propria, thereby maintaining a healthy gut. An important functional and measurable feature of the gastro-intestinal barrier constitutes intestinal permeability, which is influenced by both the gut microbiota and mucosal immunity.1 Intestinal microbiota play a pivotal role in preserving gut epithelial barrier integrity. A strong link exists betweenmicrobial dysbiosis and intestinal permeability.2 Intestinal dysbiosis in CD is characterized by increased numbers of (potentially) pathogenic bacteria, such as several members of the Enterobacteriaceae, and a decreased abundance of commensal bacteria, such as Faecalibacterium prausnitzii. Decreased abundancy of Faecalibacteriumprausnitzii is consistently observed in CD and is associated with increased inflammation and presumably disrupted intestinal barrier integrity.3,4 Similarly, Enterobacteriaceae, e.g. adherent-invasive Escherichia coli (AIEC), are known to possess multiple pathogenic mechanisms that can lead to loss of intestinal barrier function.5 These typical shifts of many bacterial species that are characteristic for CD dysbiosis are putatively related to either gain or loss of intestinal epithelial barrier function (such as Faecalibacterium prausnitzii and Enterobacteriaceae (e.g. Escherichia coli), respectively).6,7 An impaired intestinal permeability has been associated with many gastro-intestinal (GI) and non-GI diseases.1 In inflammatory bowel disease (IBD) research, there has been much scientific interest in unraveling the complex association between a comprised gut wall integrity and mucosal inflammation. Until now, however, it is not fully understood whether a defective mucosal barrier in IBD promotes intestinal inflammation or that impaired barrier function is secondary to the inflammatory process.8,9 Nonetheless, the link between an increased intestinal permeability and increased inflammatory activity is well-established.10 There is also increasing evidence that an increased intestinal permeability to macromolecules precedes the onset of IBD and/or is a sign of subclinical disease activity. It may therefore be used as an early predictor of clinical relapses in IBD patients.11-14 This is illustrated by the fact that a subset of clinically healthy first-degree relatives of Crohn’s disease patients are genetically predisposed to an increased intestinal permeability as compared to healthy controls.15,16 Despite this strong association, inflammatory disease activity has hitherto been monitored inconsistently in clinical practice. Since a poor association exists between clinically active disease and observed endoscopic disease activity, non-invasive biomarkers have increasingly been studied to predict active intestinal inflammation in CD.17 For instance, biochemical disease parameters such as the fecal calprotectin (FC) level and serum C-reactive protein (CRP) are being widely utilized, since these markers correlate significantly with endoscopically active disease.18-20 In this study, we use fecal calprotectin levels as an accurate indirect measure of inflammatory disease activity.21,22 Currently, orally administered tracers for intestinal permeability play no significant role in monitoring disease exacerbations in CD, but may aid in the diagnostic accuracy of the currently available panel of non-invasive disease biomarkers and help predict CD disease course.19,23,24 The clinical utility and validity of these non-invasive tests for intestinal permeability are still not fully 52Cr-EDTA intestinal permeability in Crohn’s disease
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