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Effect of Gliadin on Permeability of Intestinal Biopsy Explants from Celiac Disease Patients and Patients with Non-Celiac Gluten Sensitivity
by
Justin Hollon 1,*, Elaine Leonard Puppa 2, Bruce Greenwald 3, Eric Goldberg 3, Anthony Guerrerio 4 and Alessio Fasano 5
Justin Hollon 1,*, Elaine Leonard Puppa 2, Bruce Greenwald 3, Eric Goldberg 3, Anthony Guerrerio 4 and Alessio Fasano 5
1
Department of Pediatric Gastroenterology, Naval Medical Center Portsmouth, 620 John Paul Jones Circle, Portsmouth, VA 23708, USA
2
University of Maryland School of Medicine, Baltimore, MD 21201, USA
3
Division of Gastroenterology and Hepatology, University of Maryland School of Medicine, Baltimore, MD 21201, USA
4
Division of Pediatric Gastroenterology and Nutrition, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
5
Center for Celiac Research, Massachusetts General Hospital and Division of Pediatric Gastroenterology and Nutrition, Massachusetts General Hospital for Children, Boston, MA 02114, USA
*
Author to whom correspondence should be addressed.
Nutrients 2015, 7(3), 1565-1576; https://doi.org/10.3390/nu7031565
Received: 28 October 2014 / Revised: 5 February 2015 / Accepted: 11 February 2015 / Published: 27 February 2015
(This article belongs to the Special Issue Gluten Related Disorders: People Shall not Live on Bread Alone)
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.
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Keywords:
celiac disease; gluten sensitivity; IL-10
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MDPI and ACS Style
Hollon, J.; Puppa, E.L.; Greenwald, B.; Goldberg, E.; Guerrerio, A.; Fasano, A. Effect of Gliadin on Permeability of Intestinal Biopsy Explants from Celiac Disease Patients and Patients with Non-Celiac Gluten Sensitivity. Nutrients 2015, 7, 1565-1576.
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