Altered permeability in inflammatory bowel disease: pathophysiology and clinical implications

Mankertz, Joachim; Schulzke, Jörg–Dieter

doi:10.1097/mog.0b013e32816aa392

Cited by 267 publications

(221 citation statements)

References 64 publications

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“…Addition of antihypertensive medication (n ¼ 2) and use of non-steroidal anti-inflammatory drug (n ¼ 1) as covariates in the repeated measures analysis of variance did not change the results, but drug or disease interactions should be considered in certain populations as increased urinary disaccharide excretion is associated with several gastrointestinal disorders, such as Crohn's and gastric disease. 19,20 We conclude that BMI does not affect the validity of sucrose and fructose excretions in 24-h urine collections used as biomarkers to estimate total sugar consumption. Urinary biomarkers of sugar consumption AMCP Joosen et al…”

Section: Discussionmentioning

confidence: 99%

Urinary sucrose and fructose as biomarkers of sugar consumption: comparison of normal weight and obese volunteers

et al. 2008

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Using urinary sugars as a biomarker of consumption, we have previously shown that obese people consume significantly more sugars than individuals of normal weight. However, there is concern that recovery of this biomarker may differ between normal weight and obese individuals. A total of 19 subjects, divided into two groups according to their body mass index (BMI) (normal weight BMIp25 kg/m 2 , n ¼ 10; obese BMIX30 kg/m 2 , n ¼ 9), participated in a randomized crossover dietary intervention study of three diets providing 13, 30 and 50% of energy from sugars for 4 days each while living in a volunteer suite. The mean urinary sucrose and fructose excretions in 24-h urine increased with increasing sugar consumption over the three dietary periods in both BMI groups and were significantly different between the diets (Po0.01). There was no significant interaction effect of BMI class on the mean urinary excretions of these sugars with different sugar intakes, either as absolute values or expressed as a percentage of total sugar intake. In conclusion, BMI does not affect the validity of sucrose and fructose excretions in 24-h urine collections used as biomarkers to estimate total sugar consumption.

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Section: Discussionmentioning

confidence: 99%

Urinary sucrose and fructose as biomarkers of sugar consumption: comparison of normal weight and obese volunteers

et al. 2008

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“…Occludin and CLDN8 were down-regulated and CLDN2 was up-regulated in patients with mild to moderate CD [108]. These changes might be mediated by inflammatory cytokines, because TNFa and IFNc change the barrier function through MLCK activation [109], and TNFa increases CLDN2 expression [110]. In CD patients, antiTNFa antibody not only regulates inflammation but also improves intestinal mucosal permeability [111].…”

Section: Inflammatory Bowel Disease (Ibd)mentioning

confidence: 99%

Gastrointestinal mucosal barrier function and diseases

2016

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The gastrointestinal mucosal barrier plays an essential role in the separation of the inside of the body from the outside environment. Tight junctions (TJs) are the most important component for construction of a constitutive barrier of epithelial cells, and they regulate the permeability of the barrier by tightly sealing the cell-cell junctions. TJ proteins are represented by claudins, occludin, junctional adhesion molecules, and scaffold protein zonula occludens. Among these TJ proteins, claudins are the major components of TJs and are responsible for the barrier and the polarity of the epithelial cells. Gastrointestinal diseases including reflux esophagitis, inflammatory bowel disease, functional gastrointestinal disorders, and cancers may be regulated by these molecules, and disruption of their functions leads to chronic inflammatory conditions and chronic or progressive disease. Therefore, regulation of the barrier function of epithelial cells by regulating the expression and localization of TJ proteins is a potential new target for the treatment of these diseases. Treatment strategies for these diseases might thus be largely altered if symptom generation and/or immune dysfunction could be regulated through improvement of mucosal barrier function. Since TJ proteins may also modify tumor infiltration and metastasis, other important goals include finding a good TJ biomarker of cancer progression and patient prognosis, and developing TJ protein-targeted therapies that can modify patient prognosis. This review summarizes current understanding of gastrointestinal barrier function, TJ protein expression, and the mechanisms underlying epithelial barrier dysregulation in gastrointestinal diseases.

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“…In IBD, altered permeability increases the infiltration of proinflammatory stimuli to the underlying immune cells, triggering further cytokine-induced changes to the tight junction (TJ) and a vicious cycle of mucosal barrier dysfunction and inflammation (2,21). Similarly in the diarrhea-predominant form of IBS, altered permeability of the epithelium is thought to increase the load of bacterial and dietary antigens in the lamina propria, leading to the activation of mucosal immune responses involved in the generation of diarrhea and visceral hypersensitivity (1).…”

Section: Translational Highlights This Study Demonstrates That In Thmentioning

confidence: 99%

Regulation of human epithelial tight junction proteins by Lactobacillus plantarum in vivo and protective effects on the epithelial barrier

Karczewski

Troost

Konings

et al. 2010

American Journal of Physiology-Gastrointestinal and Liver Physi

519

390

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Karczewski J, Troost FJ, Konings I, Dekker J, Kleerebezem M, Brummer RM, Wells JM. Regulation of human epithelial tight junction proteins by Lactobacillus plantarum in vivo and protective effects on the epithelial barrier. Am J Physiol Gastrointest Liver Physiol 298: G851-G859, 2010. First published March 11, 2010; doi:10.1152/ajpgi.00327.2009.-Lactobacillus plantarum, a commensal bacterium of humans, has been proposed to enhance the intestinal barrier, which is compromised in a number of intestinal disorders. To study the effect of L. plantarum strain WCFS1 on human barrier function, healthy subjects were administered L. plantarum or placebo in the duodenum for 6 h by means of a feeding catheter. The scaffold protein zonula occludens (ZO)-1 and transmembrane protein occludin were found to be significantly increased in the vicinity of the tight-junction (TJ) structures, which form the paracellular seal between cells of the epithelium. In an in vitro model of the human epithelium, L. plantarum induced translocation of ZO-1 to the TJ region; however, the effects on occludin were minor compared with those seen in vivo. L. plantarum was shown to activate Toll-like receptor 2 (TLR2) signaling, and treatment of Caco-2 monolayers with the TLR2 agonist Pam 3 -Cys-SK4(PCSK) significantly increased fluorescent staining of occludin in the TJ. Pretreatment of Caco-2 monolayers with L. plantarum or PCSK significantly attenuated the effects of phorbol ester-induced dislocation of ZO-1 and occludin and the associated increase in epithelial permeability. Our results identifying commensal bacterial stimulation of TLR2 in the gut epithelium as a regulator of epithelial integrity have important implications for understanding probiotic mechanisms and the control of intestinal homeostasis. epithelium; intestine

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Altered permeability in inflammatory bowel disease: pathophysiology and clinical implications

Cited by 267 publications

References 64 publications

Urinary sucrose and fructose as biomarkers of sugar consumption: comparison of normal weight and obese volunteers

Urinary sucrose and fructose as biomarkers of sugar consumption: comparison of normal weight and obese volunteers

Gastrointestinal mucosal barrier function and diseases

Regulation of human epithelial tight junction proteins by Lactobacillus plantarum in vivo and protective effects on the epithelial barrier

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