Original ResearchFull Report: Basic and Translational—Alimentary TractDuodenal Bacteria From Patients With Celiac Disease and Healthy Subjects Distinctly Affect Gluten Breakdown and Immunogenicity
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Mice
C57BL/6 germ-free mice were generated by axenic 2-cell embryo transfer technique, as described previously,14 and maintained in flexible film isolators at the McMaster University Axenic Gnotobiotic Unit. Germ-free status was evaluated weekly by a combination of culture and culture-independent techniques.14, 15 We used mice colonized with an 8 strain-murine microbiota (altered Schaedler flora [ASF])16 as controls. All mice had unlimited access to a gluten-free autoclaved mouse diet (Harlan,
Commensals and Opportunistic Pathogens Contribute to Gluten Metabolism in the Gut
To investigate the small intestinal gluten metabolic activity of the strains selected in this study, we colonized germ-free C57BL/6 mice (n = 13/group) with P aeruginosa X-46.1, a Proteobacteria isolated from the duodenum of CD patients; Staphylococcus epidermidis X-35.1 and Staphylococcus warneri X-18.3 from the duodenum of CD patients; and Lactobacillus rhamnosus X-32.2 and Lactobacillus fermentum X-39.3 from the duodenum of non-celiac healthy volunteers (Supplementary Table 1). Mice were
Discussion
The role of intestinal microbiota in health and disease has been one of most studied areas in the past decade,39 and its contribution to food sensitivities40 and autoimmune disorders, such as CD,41 is emerging. CD represents a unique model to study diet-induced intestinal inflammation and autoimmunity because the main environmental trigger, gluten, has been identified as well as the molecular mechanisms underlying peptide association with MHC class II and subsequent T-cell activation.6 Here we
Acknowledgments
The authors thank McMaster’s AGU staff Joe Notarangelo, Sarah Armstrong, Mike Deibert, and Dr Carolyn Southward for their support with germ-free mouse breeding and gnotobiotic experiments. The authors also thank the CD volunteers who participated in this study.
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Conflicts of interest This author discloses the following: Jason A. Tye-Din is a co-inventor of patents pertaining to the use of gluten peptides in therapeutics, diagnostics, and non-toxic gluten, and is a shareholders of Nexpep Pty Ltd and a consultant to ImmusanT, Inc. Full disclosure was provided to all study participants. The remaining authors disclose no conflicts.
Funding Alberto Caminero received a Canadian Association of Gastroenterology/Canadian Institutes of Health Research (CIHR) postdoctoral fellowship and a New Investigator Award by the Canadian Celiac Association. JLM received a Boris Family scholarship. Chad W. Johnston received a CIHR doctoral research award. Detlef Schuppan received a grant from the German Ministry for Research and Development (BMBF): Clinical Development of Transglutaminase Inhibitors for the Treatment of Celiac Disease. Jason A. Tye-Din and Amy K. Russell were supported by Coeliac Australia, the National Health and Medical Resarch Council Independent Research Institutes Infrastructure Support Scheme grant 361646 and Victorian State Government Operational Infrastructure Support. Elena F. Verdu holds a Canada research Chair. The work was funded by a CIHR grant MOP#142773 to Elena F. Verdu.
Author names in bold designate shared co-first authorship.