Divergence of gut permeability and mucosal immune gene expression in two gluten-associated conditions: Celiac disease and gluten sensitivity – Source: BMC Medicine, Mar 11, 2011

[Note: To read the full text of this free access article, click HERE. ‘Innate immunity’ involves general defensive barriers like stomach acid, coughing, mucus, to keep harmful materials from entering the body. ‘Acquired immunity’ involves antibodies or other defenses against specific invaders, developed after initial exposure.]


Celiac disease (CD) is an autoimmune enteropathy [disease of the intestine] triggered by the ingestion of gluten.

Gluten-sensitive individuals (GS) cannot tolerate gluten and may develop gastrointestinal symptoms similar to those in celiac disease, but the overall clinical picture is generally less severe and is not accompanied by the concurrence of tissue transglutaminase autoantibodies or autoimmune comorbidities.

By studying and comparing mucosal expression of genes associated with intestinal barrier function, as well as innate and adaptive immunity in celiac disease compared with gluten-sensitivity, we sought to better understand the similarities and differences between these two gluten-associated disorders.

Methods: Celiac disease patients, gluten-sensitive individuals and healthy, gluten-tolerant individuals were enrolled in this study.

• Intestinal permeability [‘leaky gut’] was evaluated using a lactulose and mannitol probe,

• And mucosal biopsy specimens were collected to study the expression of genes involved in barrier function and immunity.


• Unlike Celiac disease, gluten sensitivity is not associated with increased intestinal permeability.

• In fact, this was significantly reduced in gluten sensitive individuals compared with controls (P = 0.0308), paralleled by significantly increased expression of claudin (CLDN) 4 (P = 0.0286). [Claudins are proteins that contribute to tight junctions between cells in the lining of the gut and other organs.]

• Relative to controls, adaptive immunity markers interleukin (IL)-6 (P = 0.0124) and IL-21 (P = 0.0572) were expressed at higher levels in celiac disease but not in gluten sensitivity, while expression of the innate immunity marker Toll-like receptor (TLR) 2 was increased in gluten sensitivity but not in celiac disease (P = 0.0295).

• Finally, expression of the T-regulatory cell marker FOXP3 was significantly reduced in gluten sensitivity relative to controls (P = 0.0325) and celiac disease patients (P = 0.0293).

Conclusions: This study shows that the two gluten-associated disorders, celiac disease and gluten sensitivity, are different clinical entities, and it contributes to the characterization of gluten sensitivity as a condition associated with prevalent gluten-induced activation of innate, rather than adaptive, immune responses in the absence of detectable changes in mucosal barrier function.

Source: BMC Medicine, Mar 9, 2011;9(23). 10.1186/1741-7015-9-23, by Sapone A, Lammers KM, Casolaro V, Cammarota M, Giuliano MT, De Rosa M, Stefanile R, Mazzarella G, Tolone C, Russo MI, Esposito P, Ferraraccio F, Carteni M, Riegler G, de Magistris L, Fasano A. Departments of Internal and Experimental Medicine Magrassi-Lanzara, Experimental Medicine, and Pediatrics, and Servizio di Endoscopia Digestiva Morfopatologia, Seconda Università degli Studi di Napoli, Naples, Italy; Mucosal Biology Research Center, University of Maryland School of Medicine, Baltimore; Johns Hopkins Asthma and Allergy Center, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA; Institute of Food, Consiglio Nazionale delle Ricerche (CNR), Avellino, Italy. [Email: afasano@mbrc.umaryland.edu]

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