Is small intestinal permeability really increased in relatives of patients with Crohn's disease?

May, Gary R.; Sutherland, Lloyd R.; Meddings, Jon

doi:10.1016/0016-5085(93)90638-s

Cited by 285 publications

(185 citation statements)

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“…The broken horizontal line corresponds to a lactulose/mannitol ratio of 0.022 that was proposed in the literature as the upper limit in a large number of healthy adults. 12 Values in non-pregnant controls fell below this line or immediately over it (one case), whereas one normal pregnant and five patients with ICP gave values over the upper limit.…”

Section: Resultsmentioning

confidence: 85%

“…An increased intestinal permeability has been observed in patients with enteric damage, such as in inflammatory bowel disease and coeliac disease, in intestinal infections, during the intake of aspirin, nonsteroidal anti-inflammatory drugs, or alcohol, in malnourished individuals, after burns, during total parenteral nutrition, in critically ill patients, and also in various extraintestinal diseases. [5][6][7][8][9][10][11][12][13][14][15][16][17] These conditions determine a "leaky gut syndrome" with increased portal uptake of inflammatory mediators, bacteria, antigens, and toxins, enhancing the systemic distribution of potentially injurious macromolecules.…”

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confidence: 99%

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Is a leaky gut involved in the pathogenesis of intrahepatic cholestasis of pregnancy?†‡§

et al. 2006

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I ntrahepatic cholestasis of pregnancy (ICP) is a rare disorder of unknown cause that may develop during the third or second trimester of pregnancy and resolves rapidly after delivery. The chief complaint is pruritus, and serum liver tests reveal a mild cholestasis with increased levels of bile salts and aminotransferases. ICP may cause fetal distress, with stillbirths or premature deliveries leading to increased perinatal morbidity and mortality. 1,2 The pathogenesis of ICP appears to be multifactorial. Potential contributors include a genetic predisposition interacting with the effects of estrogen and progesterone metabolites on bile secretory mechanisms. 3 The influence of environmental factors has been suggested by the observation of a seasonal variability in the incidence of ICP, with highest rates reported during winter, a recurrence rate of only 45% to 70% in subsequent pregnancies of multiparous women, and the decrease in the prevalence of ICP detected in Sweden and Chile during recent decades. 4 Therefore, identifying factors that may explain these epidemiological changes appear to be important.The gastrointestinal mucosal epithelium is an essential barrier that normally restricts the passage of harmful molecules into the mucosa and systemic circulation. An increased intestinal permeability has been observed in patients with enteric damage, such as in inflammatory From the

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Section: Resultsmentioning

confidence: 85%

mentioning

confidence: 99%

Is a leaky gut involved in the pathogenesis of intrahepatic cholestasis of pregnancy?†‡§

et al. 2006

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“…Approximately 50% of patients with active Crohn's disease have an increased small intestinal permeability (Bjarnason et al, 1983). Moreover, it has been shown that an increase in intestinal permeability precedes clinical manifestation of Crohn's disease (May et al, 1993). A compromised intestinal barrier function is regarded as an etiological factor in Crohn's disease (Meddings, 1997), celiac disease (Smecuol et al, 1997), viral gastroenteritis (Isolauri et al, 1989) and food allergy (Crowe & Perdue, 1992).…”

Section: Discussionmentioning

confidence: 99%

Recombinant human lactoferrin ingestion attenuates indomethacin-induced enteropathy in vivo in healthy volunteers

2003

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Objective: To determine whether recombinant human lactoferrin ingestion inhibits nonsteroidal antiinflammatory drugs (NSAID)-induced gastroenteropathy in vivo in healthy volunteers as a model for disorders associated with a rise in permeability of the stomach and the small intestine. Design: A randomized crossover dietary intervention. Subjects and interventions: In all, 15 healthy volunteers (age 2371.4 y) were tested. A sucrose and a lactulose/rhamnose (L/R) permeability test was performed to assess gastroduodenal and small intestine permeability as indicator of NSAID-induced gastroenteropathy. All subjects consumed standardized meals for 2 days. On the second day at time ¼ À24 h each subject ingested a drink containing 5 g recombinant human lactoferrin or placebo during breakfast. At t ¼ À9 h, subjects ingested the same drink with 75 mg of the NSAID indomethacin and after an overnight fast at t ¼ À1 h subjects consumed the drink and 50 mg indomethacin. After 1 h, at t ¼ 0, a permeability test was performed. Results: Small intestine permeability after indomethacin and placebo was significantly higher (L/R ratio ¼ 0.036; 0.014-0.092, Po0.05) compared to the permeability observed after ingestion of indomethacin and lactoferrin (0.028; 0.015-0.056), whereas gastroduodenal permeability did not differ between the two interventions (P ¼ 0.3). Conclusion: Oral recombinant human lactoferrin supplementation during a short-term indomethacin challenge reduced the NSAID-mediated increase in small intestinal permeability and hence may provide a nutritional tool in the treatment of hyperpermeability-associated disorders. Sponshorship: Grant and human recombinant lactoferrin donated from Agennix Inc., Houston, TX.

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“…14 In addition, enteric loss of water, albumin, and ␣ 1 -antitrysin indicate that mucosal inflammation increases efferent movement of macromolecules into the lumen. [15][16][17] The pro-inflammatory transcription factor nuclear factor (NF-B) is a central regulator of host defense responses in epithelial cells. 1 Epithelial NF-B activation occurs in response to enteric pathogens (enteropathogenic Escherichia coli, Salmonella, etc), toll-like receptor signaling, and cytokines such as interleukin-6 and tumor necrosis factor (TNF).…”

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confidence: 99%

Epithelial NF-κB Enhances Transmucosal Fluid Movement by Altering Tight Junction Protein Composition after T Cell Activation

Tang¹,

Clayburgh

Mittal³

et al. 2010

The American Journal of Pathology

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In inflammatory bowel disease (IBD) , aberrant activation of innate and adaptive immune responses enhances mucosal permeability through mechanisms not completely understood. To examine the role of epithelial nuclear factor (NF-B) in IBD-induced enhanced permeability , epithelial-specific IB␣ mutant (NF-B super repressor) transgenic (TG) mice were generated. NF-kB activation was inhibited in TG mice, relative to wild-type mice , following T cell-mediated immune cell activation using an anti-CD3 monoclonal antibody. Furthermore , epithelial NF-B super repressor protein inhibited diarrhea and blocked changes in transepithelial resistance and transmucosal flux of alexa350 (0.35 kDa) and dextran3000 (3 kDa). In vivo perfusion loop studies in TG mice revealed reversed net water secretion and reduced lumenal flux of different molecular probes (bovine serum albumin, alexa350, and dextran3000). Cell-imaging and immunoblotting of low-density, detergent-insoluble membrane fractions confirmed that tight junction proteins (occludin, claudin-1 and zona occludens-1) are internalized through an NF-B-dependent pathway. Taken together, these data suggest that IBD-associated diarrhea results from NF-B-mediated tight junction protein internalization and increased paracellular permeability. Thus, reduction of epithelial NF-B activation in IBD may repair defects in epithelial barrier function, reduce diarrhea, and limit protein (eg, serum albumin) losses. Epithelial NF-B activation induced by mucosal T cells, therefore, actively plays a role in opening paracellular spaces to promote transmucosal fluid effux into the intestinal lumen.

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Is small intestinal permeability really increased in relatives of patients with Crohn's disease?

Cited by 285 publications

References 11 publications

Is a leaky gut involved in the pathogenesis of intrahepatic cholestasis of pregnancy?†‡§

Is a leaky gut involved in the pathogenesis of intrahepatic cholestasis of pregnancy?†‡§

Recombinant human lactoferrin ingestion attenuates indomethacin-induced enteropathy in vivo in healthy volunteers

Epithelial NF-κB Enhances Transmucosal Fluid Movement by Altering Tight Junction Protein Composition after T Cell Activation

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