Duodenal bacteria from patients with celiac disease and healthy subjects distinctly affect gluten breakdown and immunogenicity
- Caminero, A; Galipeau, HJ; McCarville, JL; Johnston, CW; Bernier, SP; Russell, AK; Jury, J; Herran, AR; Casqueiro, J; Tye-Din, JA; Surette, MG; Magarvey, NA; Schuppan, D; Verdu, EF;
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- BACKGROUND & AIMS: Partially-degraded gluten peptides from cereals trigger celiac disease (CeD), an autoimmune enteropathy occuring in genetically susceptible persons. Susceptibility genes are necessary but not sufficient to induce CeD and additional environmental factors related to unfavorable alterations in the microbiota have been proposed. We investigated gluten metabolism by opportunistic pathogens and commensal duodenal bacteria and characterized the capacity of the produced peptides to activate gluten-specific T-cells from CeD patients. METHODS: We colonized germ-free C57BL/6 mice with bacteria isolated from the small intestine of CeD patients or healthy controls, selected by their in vitro gluten-degrading capacity. After gluten gavage, gliadin amount and proteolytic activities were measured in intestinal contents. Peptides produced by bacteria used in mouse colonizations from the immunogenic 33-mer gluten peptide were characterized by LC-MS/MS and their immunogenic potential was evaluated using peripheral blood mononuclear cells from celiac patients after receiving a 3-day gluten challenge. RESULTS: Bacterial colonizations produced distinct gluten degradation patterns in the mouse small intestine. Pseudomonas aeruginosa (Psa), an opportunistic pathogen from CeD patients, exhibited elastase activity and produced peptides that better translocated the mouse intestinal barrier. Psa-modified gluten peptides activated gluten-specific T-cells from CeD patients. In contrast, Lactobacillus spp. from the duodenum of non-CeD controls degraded gluten peptides produced by human and Psa proteases, reducing their immunogenicity. CONLUSIONS: Small intestinal bacteria exhibit distinct gluten metabolic patterns in vivo, increasing or reducing gluten peptide immunogenicity. This microbe-gluten-host interaction may modulate autoimmune risk in genetically susceptible persons and may underlie the reported association of dysbiosis and CeD.
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Creation Date: 2016-08-10 04:12:50Last Modified: 2018-07-11 09:30:21