title: Duodenal Bacteria From Patients With Celiac Disease and Healthy Subjects Distinctly Affect Gluten Breakdown and Immunogenicity.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Alberto
authors.initials: A
authors.lastname: Caminero
authors.affiliation: Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Heather J
authors.initials: HJ
authors.lastname: Galipeau
authors.affiliation: Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Justin L
authors.initials: JL
authors.lastname: McCarville
authors.affiliation: Department of Biochemistry and Biomedical Sciences, M. G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Chad W
authors.initials: CW
authors.lastname: Johnston
authors.affiliation: Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Steve P
authors.initials: SP
authors.lastname: Bernier
authors.affiliation: Immunology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia; Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Amy K
authors.initials: AK
authors.lastname: Russell
authors.affiliation: Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Jury
authors.affiliation: Área de Microbiología, Facultad de Biología y Ciencias Ambientales, Universidad de León, León, Spain.
authors.forename: Alexandra R
authors.initials: AR
authors.lastname: Herran
authors.affiliation: Área de Microbiología, Facultad de Biología y Ciencias Ambientales, Universidad de León, León, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Casqueiro
authors.affiliation: Immunology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia; Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia; Department of Gastroenterology, The Royal Melbourne Hospital, Parkville, Victoria, Australia.
authors.forename: Jason A
authors.initials: JA
authors.lastname: Tye-Din
authors.affiliation: Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada; Department of Biochemistry and Biomedical Sciences, M. G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Surette
authors.affiliation: Department of Biochemistry and Biomedical Sciences, M. G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Nathan A
authors.initials: NA
authors.lastname: Magarvey
authors.affiliation: Institute for Translational Immunology and Research Center for Immunotherapy, University Medical Center, Johannes Gutenberg University, Mainz, Germany.
authors.forename: Detlef
authors.initials: D
authors.lastname: Schuppan
authors.affiliation: Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada. Electronic address: verdue@mcmaster.ca.
authors.forename: Elena F
authors.initials: EF
authors.lastname: Verdu
mesh_terms: D000818:Animals; D018988:Bacterial Translocation; D016022:Case-Control Studies; D002446:Celiac Disease / Q000235:genetics / Q000276:immunology* / Q000382:microbiology*; D004386:Duodenum / Q000382:microbiology*; D005983:Glutens / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D055261:Immunogenetic Phenomena; D007778:Lactobacillus / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D011550:Pseudomonas aeruginosa / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D005983:Glutens
keywords: Celiac Disease; Gluten Metabolism; Intestinal Inflammation; Intestinal Microbiota