scholarly journals Increased gut permeability in Crohn's disease: is TNF the link?

Gut ◽  
2004 ◽  
Vol 53 (12) ◽  
pp. 1724-1725 ◽  
Author(s):  
P R Gibson
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Gut Permeability

scholarly journals Chromogranin A regulates gut permeability via the antagonistic actions of its proteolytic peptides

2020 ◽  
Author(s):  
Elke M. Muntjewerff ◽  
Kechun Tang ◽  
Lisanne Lutter ◽  
Gustaf Christoffersson ◽  
Mara J.T. Nicolasen ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Chromogranin A ◽  
Intestinal Barrier ◽  
Enteroendocrine Cells ◽  
Leaky Gut ◽  
Gut Permeability ◽  
Gut Barrier ◽  
Ultrastructural Studies ◽  
New Findings

AbstractBackground and AimsA ‘leaky’ gut barrier has been implicated in the initiation and progression of a multitude of diseases, e.g., inflammatory bowel disease, irritable bowel syndrome, celiac disease, and colorectal cancers. Here we asked how Chromogranin A (CgA), a major hormone produced by the enteroendocrine cells, and Catestatin (CST), the most abundant CgA-derived proteolytic peptide, affect the gut barrier.Methods and ResultsUltrastructural studies on the colons from Catestatin (CST: hCgA352-372) knockout (CST-KO) mice revealed (i) altered morphology of tight (TJ) and adherens (AJ) junctions and desmosomes, indicative of junctional stress and (ii) an increased infiltration of immune cells compared to controls. Flow cytometry studies confirmed these cells to be macrophages and CD4+ T cells. Gene expression studies confirmed that multiple TJ-markers were reduced, with concomitant compensatory elevation of AJ and desmosome markers. Consistently, the levels of plasma FITC-dextran were elevated in the CST-KO mice, confirming leakiness’ of the gut. Leaky gut in CST-KO mice correlated with inflammation and a higher ratio of Firmicutes to Bacteroidetes, a dysbiotic pattern commonly encountered in a multitude of diseases. Supplementation of CST-KO mice with recombinant CST reversed this leakiness and key phenotypes. Supplementation of CgA-KO mice with either CST alone, or with the pro-inflammatory proteolytic CgA fragment pancreastatin (PST: CgA250-301) showed that gut permeability is regulated by the antagonistic roles of these two peptide hormones: CST reduces and PST increases leakiness.ConclusionWe conclude that the enteroendocrine cell-derived hormone, CgA regulates gut permeability. CST is both necessary and sufficient to reduce the leakiness. CST acts primarily via antagonizing the effects of PST.What you need to knowBackground and ContextThe intestinal barrier is disrupted in many intestinal diseases such as Crohn’s disease. Chromogranin A (CgA) is produced by enteroendocrine cells in the gut. CgA is proteolytically cleaved into bioactive peptides including catestatin (CST) and pancreastatin (PST). The role of CgA in the gut is unknown.New findingsCgA is efficiently processed to CST in the gut and this processing might be decreased during active Crohn’s disease. CST promotes epithelial barrier function and reduces inflammation by counteracting PST.LimitationsThe complete mechanism of intestinal barrier regulation by CST likely involves a complex interplay between the enteroendocrine system, metabolism, the epithelium, the immune system and the gut microbiota.ImpactOur findings indicate that CST is a key modulator of the intestinal barrier and immune functions that correlates with disease severity of Crohn’s disease. CST could be a target for therapeutic interventions in Crohn’s disease.

Altered gut microbiota and gut permeability in Crohn’s disease patients in clinical remission

2021 ◽  
Vol 46 ◽  
pp. S662
Author(s):  
I.M.G. Rocha ◽  
D.C. Fonseca ◽  
R. Torrinhas ◽  
A.O.M.C. Damião ◽  
L. Callado ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Gut Microbiota ◽  
Clinical Remission ◽  
Gut Permeability

scholarly journals Serum Zonulin Measured by Commercial Kit Fails to Correlate With Physiologic Measures of Altered Gut Permeability in First Degree Relatives of Crohn's Disease Patients

2021 ◽  
Vol 12 ◽  
Author(s):  
Namita Power ◽  
Williams Turpin ◽  
Osvaldo Espin-Garcia ◽  
Michelle I. Smith ◽  
Kenneth Croitoru ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Intestinal Permeability ◽  
Barrier Function ◽  
Intestinal Barrier ◽  
Fractional Excretion ◽  
Fatty Acid Binding Proteins ◽  
Limited Information ◽  
Gut Permeability ◽  
Fatty Acid Binding

Intestinal epithelial cell tight junctions (TJs) contribute to the integrity of the intestinal barrier allowing for control of the physical barrier between external antigens or bacterial products and the internal environment. Zonula occludens-1 (ZO-1) is a protein that modulates intestinal TJs, and serum levels of ZO-1 has been suggested as a biomarker of disrupted barrier function in humans. Previous studies suggested that increased intestinal permeability was associated with evidence of TJ abnormalities. However, there is limited information on the serological measurement of ZO-1 and its relation to other tests of barrier function in healthy subjects. We investigated the correlation of serum ZO-1, with physiologic measures of intestinal permeability (as the ratio of the fractional excretion of lactulose-mannitol or LMR) in a cohort of 39 healthy FDRs of Crohn's disease (CD) patients. No significant correlation was found between LMR and ZO-1 levels (r2 = 0.004, P < 0.71), or intestinal fatty acid binding proteins (I-FABP) (r2 = 0.004, P < 0.71). In conclusion, our data show that ZO-1 and I-FABP are not a marker of gut permeability as defined by LMR.

scholarly journals A case for improved assessment of gut permeability: a meta-analysis quantifying the lactulose:mannitol ratio in coeliac and Crohn’s disease

2022 ◽  
Vol 22 (1) ◽  
Author(s):  
Jonathan Gan ◽  
Scarlet Nazarian ◽  
Julian Teare ◽  
Ara Darzi ◽  
Hutan Ashrafian ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Clinical Evidence ◽  
Weighted Mean Difference ◽  
Meta Analysis ◽  
Mean Difference ◽  
Healthy Controls ◽  
Gut Permeability ◽  
Disease Outcomes ◽  
Standard Mean Difference

Abstract Background A widely used method in assessing small bowel permeability is the lactulose:mannitol test, where the lactulose:mannitol ratio (LMR) is measured. However, there is discrepancy in how the test is conducted and in the values of LMR obtained across studies. This meta-analysis aims to determine LMR in healthy subjects, coeliac and Crohn’s disease. Methods A literature search was performed using PRISMA guidance to identify studies assessing LMR in coeliac or Crohn’s disease. 19 studies included in the meta-analysis measured gut permeability in coeliac disease, 17 studies in Crohn’s disease. Outcomes of interest were LMR values and comparisons of standard mean difference (SMD) and weighted mean difference (WMD) in healthy controls, inactive Crohn’s, active Crohn’s, treated coeliac and untreated coeliac. Pooled estimates of differences in LMR were calculated using the random effects model. Results Pooled LMR in healthy controls was 0.014 (95% CI: 0.006–0.022) while pooled LMRs in untreated and treated coeliac were 0.133 (95% CI: 0.089–0.178) and 0.037 (95% CI: 0.019–0.055). In active and inactive Crohn’s disease, pooled LMRs were 0.093 (95% CI: 0.031–0.156) and 0.028 (95% CI: 0.015–0.041). Significant differences were observed in LMR between: (1) healthy controls and treated coeliacs (SMD = 0.409 95% CI 0.034 to 0.783, p = 0.032), (2) healthy controls and untreated coeliacs (SMD = 1.362 95% CI: 0.740 to 1.984, p < 0.001), (3) treated coeliacs and untreated coeliacs (SMD = 0.722 95% CI: 0.286 to 1.157, p = 0.001), (4) healthy controls and inactive Crohn’s (SMD = 1.265 95% CI: 0.845 to 1.686, p < 0.001), (5) healthy controls and active Crohn’s (SMD = 2.868 95% CI: 2.112 to 3.623, p < 0.001), and (6) active Crohn’s and inactive Crohn’s (SMD = 1.429 (95% CI: 0.580 to 2.278, p = 0.001). High heterogeneity was observed, which was attributed to variability in protocols used across different studies. Conclusion The use of gut permeability measurements in screening and monitoring of coeliac and Crohn’s disease is promising. LMR is useful in performing this function with significant limitations. More robust alternative tests with higher degrees of clinical evidence are needed if measurements of gut permeability are to find widespread clinical use.

scholarly journals A case for improved assessment of gut permeability – a meta-analysis quantifying the lactulose:mannitol ratio in coeliac and Crohn’s disease

2021 ◽  
Author(s):  
Jonathan Gan ◽  
Scarlet Nazarian ◽  
Julian Teare ◽  
Ara Darzi ◽  
Hutan Ashrafian ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Clinical Evidence ◽  
Weighted Mean Difference ◽  
Meta Analysis ◽  
Mean Difference ◽  
Healthy Controls ◽  
Gut Permeability ◽  
Disease Outcomes ◽  
Standard Mean Difference

Abstract Background A widely used method in assessing small bowel permeability is the lactulose:mannitol test, where the lactulose:mannitol ratio (LMR) is measured. However, there is discrepancy in how the test is conducted and in the values of LMR obtained across studies. This meta-analysis aims to determine LMR in healthy subjects, coeliac and Crohn’s disease. Methods A literature search was performed using PRISMA guidance to identify studies assessing LMR in coeliac or Crohn’s disease. 19 studies included in the meta-analysis measured gut permeability in coeliac disease, 17 studies in Crohn’s disease. Outcomes of interest were LMR values and comparisons of standard mean difference (SMD) and weighted mean difference (WMD) in healthy controls, inactive Crohn’s, active Crohn’s, treated coeliac and untreated coeliac. Pooled estimates of differences in LMR were calculated using the random effects model. Results Pooled LMR in healthy controls was 0.014 (95% CI: 0.006–0.022) while pooled LMRs in untreated and treated coeliac were 0.133 (95% CI: 0.089–0.178) and 0.037 (95% CI: 0.019–0.055). In active and inactive Crohn’s disease, pooled LMRs were 0.093 (95% CI: 0.031–0.156) and 0.028 (95% CI: 0.015–0.041). Significant differences were observed in LMR between: (i) healthy controls and treated coeliacs (SMD = 0.409 95% CI 0.034 to 0.783, p = 0.032), (ii) healthy controls and untreated coeliacs (SMD = 1.362 95% CI: 0.740 to 1.984, p < 0.001), (iii) treated coeliacs and untreated coeliacs (SMD = 0.722 95% CI: 0.286 to 1.157, p = 0.001), (iv) healthy controls and inactive Crohns (SMD = 1.265 95% CI: 0.845 to 1.686, p < 0.001), (v) healthy controls and active Crohns (SMD = 2.868 95% CI: 2.112 to 3.623, p < 0.001), and (vi) active Crohns and inactive Crohns (SMD = 1.429 (95% CI: 0.580 to 2.278, p = 0.001). High heterogeneity was observed, which was attributed to variability in protocols used across different studies. Conclusion The use of gut permeability measurements in screening and monitoring of coeliac and Crohn’s disease is promising. LMR is useful in performing this function with significant limitations. More robust alternative tests with higher degrees of clinical evidence are needed if measurements of gut permeability are to find widespread clinical use. Trial Registration Not Applicable

Analysis of Genetic Association of Intestinal Permeability in Healthy First-degree Relatives of Patients with Crohn’s Disease

2019 ◽  
Vol 25 (11) ◽  
pp. 1796-1804 ◽  
Author(s):  
Williams Turpin ◽  
Osvaldo Espin-Garcia ◽  
Larbi Bedrani ◽  
Karen Madsen ◽  
Jonathan B Meddings ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Intestinal Permeability ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
P Value ◽  
Gut Permeability ◽  
Barrier Dysfunction ◽  
First Degree Relatives

Abstract Excessive intestinal permeability or intestinal barrier dysfunction as measured by various assays has been observed in various diseases. However, little is known about the factors contributing to altered gut permeability in these diseases. Our objective was to determine the genetic determinants of altered gut permeability as measured by the lactulose mannitol fractional excretion ratio (LacMan ratio) in 1075 healthy first-degree relatives of patients with Crohn’s disease (CD). In a targeted analysis of single nucleotide polymorphisms (SNPs) located in genes associated with intestinal barrier function related or not to inflammatory bowel disease, we did not find a significant association with intestinal permeability. In an untargeted genome-wide association analysis, the top 100 associations were located in 22 genomic loci, although they were not statistically significant after correction for multiple testing (raw P values [1.8 × 10–7 - 1.4 × 10–5]. The lowest P value was obtained for rs9616637 (22q13.33, C22orf34), for which the minor allele A was associated with a decreased LacMan ratio. These results suggest that host genetic background has limited contribution toward intestinal permeability. Despite this, our study is currently the largest of its kind assessing gut permeability in vivo. It remains possible that smaller genetic effect sizes on LacMan ratio are not detectable in this sized cohort. Larger studies are warranted to identify the potential genetic contribution to intestinal permeability.

On-table endoscopy to define strictures and resection margins: experience from 178 operations for Crohn's disease using intraoperative endoscopy

2001 ◽  
Vol 3 (Supplement 2) ◽  
pp. 58-62
Author(s):  
G. Olaison ◽  
P. Andersson ◽  
P. Myrelid ◽  
K. Smedh ◽  
J. Soderholm ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Resection Margins ◽  
Intraoperative Endoscopy
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