Distinct Duodenal Bacteria in Celiac Disease, Controls
Duodenal bacteria from patients with CD have distinct effect on gluten breakdown, immunogenicity
WEDNESDAY, Oct. 5, 2016 (HealthDay News) -- Duodenal bacteria from patients with celiac disease (CD) and healthy individuals have distinct effects on gluten breakdown and immunogenicity, according to a study published in the October issue of Gastroenterology.
Alberto Caminero, Ph.D., from McMaster University in Hamilton, Canada, and colleagues colonized germ-free C57BL/6 mice with bacteria isolated from the small intestine of CD patients or healthy controls. Gliadin amount and proteolytic activities were measured in intestinal contents after gluten gavage. The peptides produced by bacteria were characterized by liquid chromatography tandem mass spectrometry, and after receiving a three-day gluten challenge their immunogenic potential was evaluated using peripheral blood mononuclear cells from celiac patients.
The researchers found that distinct gluten-degradation patterns were produced by bacterial colonizations in the mouse small intestine. An opportunistic pathogen from CD patients, Pseudomonas aeruginosa, exhibited elastase activity and produced peptides that better crossed the mouse intestinal barrier. Gluten-specific T cells from CD patients were activated by P. aeruginosa-modified gluten peptides. Gluten peptides produced by human and P. aeruginosa proteases were degraded by Lactobacillus spp from the duodenum of non-CD controls, reducing their immunogenicity.
"Small intestinal bacteria exhibit distinct gluten metabolic patterns in vivo, increasing or reducing gluten peptide immunogenicity," the authors write. "This microbe-gluten-host interaction may modulate autoimmune risk in genetically susceptible persons and may underlie the reported association of dysbiosis and CD."
One author is co-inventor of patents pertaining to the use of gluten peptides and is a shareholder of Nexpep and a consultant to ImmunsanT.