Polymeric Binders Suppress Gliadin-Induced Toxicity in the Intestinal Epithelium
Open accessAbstract
Background & aims Celiac disease is a prevalent immune disorder caused by the ingestion of gliadin-containing grains. We investigated the ability of a polymeric binder to reverse the toxic effects induced by gliadin in human intestinal cells and gliadin-sensitive HCD4-DQ8 mice.Methods Gliadin was neutralized by complexation to a linear copolymer of hydroxyethylmethacrylate (HEMA) and sodium 4-styrene sulfonate (SS). The ability of the polymeric binder to abrogate the damaging effect of gliadin on cell-cell contact was investigated in IEC-6, Caco-2/15, and primary cultured differentiated enterocytes. The efficacy of the polymeric binder in preventing gliadin-induced intestinal barrier dysfunction was assessed using gliadin-sensitive HLA-HCD4/DQ8 transgenic mice.Results Poly(hydroxyethylmethacrylate-co-styrene sulfonate) [P(HEMA-co-SS)] complexed with gliadin in a relatively specific fashion. Intestinal cells exposed to gliadin underwent profound alterations in morphology and cell-cell contacts. These changes were averted by complexing the gliadin with P(HEMA-co-SS). More importantly, the P(HEMA-co-SS) hindered the digestion of gliadin by gastrointestinal enzymes, thus minimizing the formation of immunogenic peptides. Coadministration of P(HEMA-co-SS) with gliadin to HLA-HCD4/DQ8 mice attenuated gliadin-induced changes in the intestinal barrier and reduced intraepithelial lymphocyte and macrophage cell counts.Conclusions Polymeric binders can prevent in vitro gliadin-induced epithelial toxicity and intestinal barrier dysfunction in HCD4/DQ8 mice. They have a potential role in the treatment of patients with gluten-induced disorders.
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Mouse models indicate that gluten can induce activation of innate immunity, increased small intestinal permeability, neuro-muscular dysfunction and dysbiosis in the absence of autoimmunity.
“Mouse models indicate that gluten can induce activation of innate immunity, increased small intestinal permeability,160 neuro-muscular dysfunction159 and dysbiosis161 in the absence of autoimmunity.”
From Intestinal microbiota in functional bowel disorders: a Rome foundation report (2013) · cites this paper as [160]
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- Authors
- Pinier, M., Verdu, E. F., Nasser–Eddine, M., David, C. S., Vézina, A., Rivard, N., & Leroux, J.
- Affiliations
- Université de Montréal (CA)
- McMaster University (CA)
- Mayo Clinic (US)
- Université de Sherbrooke (CA)
- Corresponding author
- Leroux, Jean–Christophe
- Venue
- Gastroenterology
- Publisher
- Elsevier BV
- Published
- 2009-01
- Volume
- 136
- Issue
- 1
- Pages
- 288-298
- ISSN
- 0016-5085 (ISSN-L)
- OpenAlex
- W2100305022
- Cited by
- 144
- References
- 40
- Citations by year
- 2026: 1 · 2025: 7 · 2024: 3 · 2023: 6 · 2022: 5 · 2021: 10 · 2020: 6 · 2019: 5 · 2018: 8 · 2017: 4 · 2016: 3 · 2015: 12 · 2014: 8 · 2013: 9 · 2012: 17
- FWCI
- 13.16
- Type
- journal article
- Language
- en
- Update notices
- erratum (2012-01-01)
- Open access
- bronze
- doi.org
- Locations
- Gastroenterology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Fonds Québécois de la Recherche sur la Nature et les Technologies
- National Institutes of Health
- Canadian Institutes of Health Research
- National Institute of Diabetes and Digestive and Kidney Diseases (DK 071003)
- Topics
- Health Sciences › Medicine › Gastroenterology › Celiac Disease Research and Management
- Life Sciences › Agricultural and Biological Sciences › Food Science › Proteins in Food Systems
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Keywords
- celiac disease, gliadin, polymer binders, intestinal barrier dysfunction, intraepithelial lymphocytes, macrophages
- MeSH terms
- Animals, Cytoskeleton, Gliadin, Humans, Intestinal Mucosa, Male, Membrane Proteins, Methacrylates, Mice, Inbred BALB C, Mice, Transgenic, Phosphoproteins, Polymers, Sulfonic Acids, Caco-2 Cells, Enterocytes, Mice, Zonula Occludens-1 Protein
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