The DOI matches its Crossref record; 68 of the 68 references it cites were found in a registry or an index.
Duodenal bacterial proteolytic activity determines sensitivity to dietary antigen through protease-activated receptor-2
Open accessAbstract
Microbe-host interactions are generally homeostatic, but when dysfunctional, they can incite food sensitivities and chronic diseases. Celiac disease (CeD) is a food sensitivity characterized by a breakdown of oral tolerance to gluten proteins in genetically predisposed individuals, although the underlying mechanisms are incompletely understood. Here we show that duodenal biopsies from patients with active CeD have increased proteolytic activity against gluten substrates that correlates with increased Proteobacteria abundance, including Pseudomonas. Using Pseudomonas aeruginosa producing elastase as a model, we show gluten-independent, PAR-2 mediated upregulation of inflammatory pathways in C57BL/6 mice without villus blunting. In mice expressing CeD risk genes, P. aeruginosa elastase synergizes with gluten to induce more severe inflammation that is associated with moderate villus blunting. These results demonstrate that proteases expressed by opportunistic pathogens impact host immune responses that are relevant to the development of food sensitivities, independently of the trigger antigen.
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In the citing paper
“elastase-like activity of the pathogen Pseudomonas aeruginosa can lead to the production of peptides following gluten metabolism with increased immunogenicity in celiac disease (CeD) patients,18”
From The emerging roles of bacterial proteases in intestinal diseases (2023) · cites this paper as [18]
In the citing paper
“Pseudomonas aeruginosa producing the metalloprotease LasB induced food sensitivity in preclinical mouse models by different mechanisms, as described below.18”
From The emerging roles of bacterial proteases in intestinal diseases (2023) · cites this paper as [18]
In the citing paper
“Duodenal biopsies from patients with active CeD have increased proteolytic activity against gluten that correlated with increased abundance of Pseudomonas, a well-known proteolytic taxon.”
From The emerging roles of bacterial proteases in intestinal diseases (2023) · cites this paper as [18]
In the citing paper
“For example, Lactobacillus strains degrade both gluten and ATI peptides, reducing their immunogenic properties.18,101”
From The emerging roles of bacterial proteases in intestinal diseases (2023) · cites this paper as [18]
In the citing paper
“Of relevance, LasB from Pseudomonas aeruginosa,18,143 and GelE from Enterococcus faecalis144 degrade the N-terminal of PAR-2, contributing to food sensitivities and intestinal inflammation in preclinical mouse models.”
From The emerging roles of bacterial proteases in intestinal diseases (2023) · cites this paper as [18]
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Self-citationStructural Basis for Gluten Intolerance in Celiac Sprue
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An ordered, nonredundant library of Pseudomonas aeruginosa strain PA14 transposon insertion mutants
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Role for protease activity in visceral pain in irritable bowel syndrome
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Self-citationIntegration of Genetic and Immunological Insights into a Model of Celiac Disease Pathogenesis
Abadie, V., Sollid, L. M., Barreiro, L. B., & Jabrì, B. (2011) · Annual Review of Immunology · doi:10.1146/annurev-immunol-040210-092915 · Cited by 529
Innate and Adaptive Immunity Cooperate Flexibly to Maintain Host-Microbiota Mutualism
Slack, E. M. C., Hapfelmeier, S., Stecher, B., Velykoredko, Y., Stoel, M., Lawson, M. A., Geuking, M. B., Beutler, B., Tedder, T. F., Hardt, W., et al. (2009) · Science · doi:10.1126/science.1172747 · Cited by 520
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Inflammatory and Microbiota-Related Regulation of the Intestinal Epithelial Barrier
Barbara, G., Barbaro, M. R., Fuschi, D., Palombo, M., Falangone, F., Cremon, C., Marasco, G., & Stanghellini, V. (2021) · Frontiers in Nutrition · doi:10.3389/fnut.2021.718356 · Cited by 446
Epidemiology, Presentation, and Diagnosis of Celiac Disease
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The Role of the Gut Microbiota in the Relationship Between Diet and Human Health
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Metadata
- Authors
- Caminero, A., McCarville, J. L., Galipeau, H. J., Deraison, C., Bernier, S. P., Constante, M., Rolland, C., Meisel, M., Murray, J. A., Yu, X. B., Alaedini, A., Coombes, B. K., Bercik, P., Southward, C. M., Ruf, W., Jabri, B., Chirdo, F. G., Casqueiro, J., Surette, M. G., Vergnolle, N., & Verdu, E. F.
- Affiliations
- McMaster University (CA)
- Université Toulouse III - Paul Sabatier (FR)
- University of Pittsburgh (US)
- Mayo Clinic (US)
- Columbia University Irving Medical Center (US)
- Scripps Research Institute (US)
- Consejo Nacional de Investigaciones Científicas y Técnicas (AR)
- Universidad de León (ES)
- Corresponding author
- Verdu, Elena F.
- ORCID
- Venue
- Nature Communications
- Published
- 2019-03-13
- Volume
- 10
- Issue
- 1
- Pages
- 1198-1198
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC6416356
- OpenAlex
- W2921973674
- Cited by
- 139
- References
- 67
- Citations by year
- 2026: 9 · 2025: 15 · 2024: 19 · 2023: 14 · 2022: 12 · 2021: 33 · 2020: 24 · 2019: 13
- FWCI
- 18.68
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- HAL (submittedVersion, cc-by)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, cc-by-nc-sa)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- CONICET Digital (CONICET) (submittedVersion, cc-by)
- Funders
- Crohn's and Colitis Foundation of America
- McMaster University
- Crohn's and Colitis Foundation (480735)
- European Commission (627487)
- Boehringer Ingelheim Stiftung
- Canadian Institutes of Health Research (MOP#142773, 142773)
- Research Executive Agency
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK067180, P30DK042086)
- FP7 Ideas: European Research Council (310973)
- 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 › Inflammatory Bowel Disease
- Keywords
- celiac disease, food sensitivity, gluten, protease-activated receptor 2, Pseudomonas aeruginosa, elastase, Proteobacteria, gut microbiota, intestinal inflammation, villous atrophy, oral tolerance, opportunistic pathogens, host-microbe interactions
- MeSH terms
- Gastrointestinal Microbiome, Host Microbial Interactions, Adult, Aged, Animals, Antigens, Bacterial Proteins, Biopsy, Celiac Disease, Colonoscopy, Dietary Proteins, Disease Models, Animal, Duodenum, Female, Germ-Free Life, Glutens, HLA-DQ Antigens, Humans, Intestinal Mucosa, Male, Metalloendopeptidases, Mice, Inbred C57BL, Mice, Transgenic, Middle Aged, Pseudomonas aeruginosa, Cohort Studies, Up-Regulation, Case-Control Studies, Mice, Inbred NOD, Receptor, PAR-2, Mice, Young Adult, Proteolysis
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