Duodenal Bacteria From Patients With Celiac Disease and Healthy Subjects Distinctly Affect Gluten Breakdown and Immunogenicity
Abstract
Background & aims Partially degraded gluten peptides from cereals trigger celiac disease (CD), an autoimmune enteropathy occurring in genetically susceptible persons. Susceptibility genes are necessary but not sufficient to induce CD, 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 CD patients.Methods We colonized germ-free C57BL/6 mice with bacteria isolated from the small intestine of CD patients or healthy controls, selected for 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 liquid chromatography tandem mass spectrometry 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, an opportunistic pathogen from CD patients, exhibited elastase activity and produced peptides that better translocated the mouse intestinal barrier. P aeruginosa-modified gluten peptides activated gluten-specific T-cells from CD patients. In contrast, Lactobacillus spp. from the duodenum of non-CD controls degraded gluten peptides produced by human and P aeruginosa proteases, reducing their immunogenicity.Conclusions 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 CD.
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Proteases expressed by pathobionts impact gluten metabolism and immune activation in the small intestine of celiac disease patients.
“These studies suggest that proteases expressed by pathobionts impact gluten metabolism and immune activation in the small intestine of CeD patients.43”
From The emerging roles of bacterial proteases in intestinal diseases (2023) · cites this paper as [43]
Microbial proteases efficiently participate in gluten metabolism in vivo by modifying gluten's mucosal absorption and immunogenicity, ultimately affecting the adaptive immune responses to gluten associated with celiac disease.
“Indeed, microbial proteases efficiently participate in gluten metabolism in vivo by modifying gluten’s mucosal absorption and immunogenicity, ultimately affecting the adaptive immune responses to gluten associated with CeD.43”
From The emerging roles of bacterial proteases in intestinal diseases (2023) · cites this paper as [43]
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- Authors
- Caminero, A., Galipeau, H. J., McCarville, J. L., Johnston, C. W., Bernier, S. P., Russell, A. K., Jury, J., Herran, A. R., Casqueiro, J., Tye-Din, J. A., Surette, M. G., Magarvey, N. A., Schuppan, D., & Verdu, E. F.
- Affiliations
- McMaster University (CA)
- Michael G. DeGroote Institute for Infectious Disease Research (CA)
- The University of Melbourne (AU)
- Universidad de León (MX)
- Johannes Gutenberg University Mainz (DE)
- Corresponding author
- Verdu, Elena F.
- ORCID
- Venue
- Gastroenterology
- Publisher
- Elsevier BV
- Published
- 2016-10
- Volume
- 151
- Issue
- 4
- Pages
- 670-683
- ISSN
- 0016-5085 (ISSN-L)
- OpenAlex
- W2460175854
- Cited by
- 250
- References
- 50
- Citations by year
- 2026: 23 · 2025: 27 · 2024: 21 · 2023: 22 · 2022: 30 · 2021: 30 · 2020: 20 · 2019: 30 · 2018: 23 · 2017: 20 · 2016: 4
- FWCI
- 28.10
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Gastroenterology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Canadian Institutes of Health Research (MOP#142773)
- Topics
- Health Sciences › Medicine › Gastroenterology › Celiac Disease Research and Management
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Keywords
- celiac disease, gluten degradation, gluten peptides, Pseudomonas aeruginosa, Lactobacillus, gut microbiota, dysbiosis, elastase activity, intestinal permeability, autoimmune enteropathy
- MeSH terms
- Animals, Celiac Disease, Duodenum, Glutens, Humans, Lactobacillus, Mice, Inbred C57BL, Pseudomonas aeruginosa, T-Lymphocytes, Case-Control Studies, Bacterial Translocation, Mice, Immunogenetic Phenomena
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