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Controlled Clinical Trial
. 2015 Feb 27;7(3):1565-76.
doi: 10.3390/nu7031565.

Effect of Gliadin on Permeability of Intestinal Biopsy Explants From Celiac Disease Patients and Patients With Non-Celiac Gluten Sensitivity

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Free PMC article
Controlled Clinical Trial

Effect of Gliadin on Permeability of Intestinal Biopsy Explants From Celiac Disease Patients and Patients With Non-Celiac Gluten Sensitivity

Justin Hollon et al. Nutrients. .
Free PMC article

Abstract

Background: Intestinal exposure to gliadin leads to zonulin upregulation and consequent disassembly of intercellular tight junctions and increased intestinal permeability. We aimed to study response to gliadin exposure, in terms of barrier function and cytokine secretion, using intestinal biopsies obtained from four groups: celiac patients with active disease (ACD), celiac patients in remission (RCD), non-celiac patients with gluten sensitivity (GS) and non-celiac controls (NC).

Methods: Ex-vivo human duodenal biopsies were mounted in microsnapwells and luminally incubated with either gliadin or media alone. Changes in transepithelial electrical resistance were monitored over 120 min. Media was subsequently collected and cytokines quantified.

Results: Intestinal explants from all groups (ACD (n = 6), RCD (n = 6), GS (n = 6), and NC (n = 5)) demonstrated a greater increase in permeability when exposed to gliadin vs. media alone. The increase in permeability in the ACD group was greater than in the RCD and NC groups. There was a greater increase in permeability in the GS group compared to the RCD group. There was no difference in permeability between the ACD and GS groups, between the RCD and NC groups, or between the NC and GS groups. IL-10 was significantly greater in the media of the NC group compared to the RCD and GS groups.

Conclusions: Increased intestinal permeability after gliadin exposure occurs in all individuals. Following gliadin exposure, both patients with gluten sensitivity and those with active celiac disease demonstrate a greater increase in intestinal permeability than celiacs in disease remission. A higher concentration of IL-10 was measured in the media exposed to control explants compared to celiac disease in remission or gluten sensitivity.

Figures

Figure 1
Figure 1
Normalized transepithelial electrical resistance (TEER) changes in human intestinal explants exposed to PT-gliadin or media alone. Explants obtained from non-celiac controls (NC), celiac patients with active disease (ACD), celiac patients in remission (RCD), and non-celiac patients with gluten sensitivity (GS). Explants were exposed to media alone (open symbols) or to PT-gliadin (filled symbols). NC (black triangle) explants demonstrated a greater increase in permeability (decrease in TEER) when exposed to PT-gliadin vs. exposure to media alone at 30, 60 and 120 min. RCD (blue diamond) explants demonstrated a greater increase in permeability when exposed to PT-gliadin vs exposure to media alone at 60 and 120 min. ACD (red circle) and GS (gold square) explants demonstrated a greater increase in permeability when exposed to PT-gliadin vs exposure to media alone at 30, 60, 90 and 120 min. Symbol denotes the median. Whiskers denote the 25th to 75th percentile. * p < 0.05.
Figure 2
Figure 2
Comparison between groups of gut permeability changes induced by either PT-gliadin or media alone measured as normalized transepithelial electrical resistance changes (∆ TEER) in human intestinal explants. Explants obtained from celiac patients in remission (RCD), non-celiac controls (NC), non-celiac patients with gluten sensitivity (GS), and celiac patients with active disease (ACD). A decrease in TEER indicates increased gut permeability. A. TEER changes of explants exposed to media alone. Explants incubated in media alone demonstrated no significant differences in permeability except between NC (black triangle) and RCD (blue diamond) groups at 30 min. B. TEER of PT-gliadin exposed explants minus TEER of corresponding explants exposed to media alone (∆ TEER). Increases in permeability in explants from the ACD group (red circle) were significantly greater than in explants from the RCD group (blue diamond) at 30, 60 and 90 min, and the NC group (black triangle) at 30 min. Increases in permeability in explants from the GS group (gold square) were significantly greater than in explants from the RCD group at 90 min. There was no significant difference in permeability between explants from the ACD and GS groups, between explants from the RCD and NC groups, or between explants from the NC and GS groups. Symbol denotes the median. Whiskers denote the 25th to 75th percentile. * p < 0.05.
Figure 3
Figure 3
Comparison between groups of IL-10 secretion from the basolateral side of biopsy explants after 120 min, with and without PT-gliadin exposure. Media collected from the basolateral sides of explants obtained from non-celiac patients with gluten sensitivity (GS), celiac patients with active disease (ACD), celiac patients in remission (RCD), and non-celiac controls (NC). The NC group showed concentrations of IL-10 significantly higher than the corresponding media from the GS and RCD group. In the graphs, the box defines the 25th and 75th percentile; center line the median; whiskers the range. * p < 0.05.

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