title: Nod1 and Nod2 signaling does not alter the composition of intestinal bacterial communities at homeostasis.
abstract: Patients with inflammatory bowel diseases (IBD) harbour intestinal bacterial communities with altered composition compared with healthy counterparts; however, it is unknown whether changes in the microbiota are associated with genetic susceptibility of individuals for developing disease or instead reflect other changes in the intestinal environment related to the disease itself. Since deficiencies in the innate immune receptors Nod1 and Nod2 are linked to IBD, we tested the hypothesis that Nod-signaling alters intestinal immune profiles and subsequently alters bacterial community structure. We used qPCR to analyze expression patterns of selected immune mediators in the ileum and cecum of Nod-deficient mice compared with their Nod-sufficient littermates and assessed the relative abundance of major bacterial groups sampled from the ileum, cecum and colon. The Nod1-deficient ileum exhibited significantly lower expression of Nod2, Muc2, α- and β-defensins and keratinocyte-derived chemokine (KC), suggesting a weakened epithelial barrier compared with WT littermates; however, there were no significant differences in the relative abundance of targeted bacterial groups, indicating that Nod1-associated immune differences alone do not promote dysbiosis. Furthermore, Nod2-deficient mice did not display any changes in the expression of immune markers or bacterial communities. Shifts in bacterial communities that were observed in this study correlated with housing conditions and were independent of genotype. These findings emphasize the importance of using F2 littermate controls to minimize environmental sources of variation in microbial analyses, to establish baseline conditions for host-microbe homeostasis in Nod-deficient mice and to strengthen models for testing factors contributing to microbial dysbiosis associated with IBD.
authors.affiliation: Department of Immunology, University of Toronto, Toronto, ON, Canada. susan.robertson@utoronto.ca
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Robertson
authors.forename: Jun Yu
authors.initials: JY
authors.lastname: Zhou
authors.forename: Kaoru
authors.initials: K
authors.lastname: Geddes
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Rubino
authors.forename: Joon Ho
authors.initials: JH
authors.lastname: Cho
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Girardin
authors.forename: Dana J
authors.initials: DJ
authors.lastname: Philpott
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000032:analysis; D058448:Biota; D005260:Female; D041981:Gastrointestinal Tract / Q000276:immunology* / Q000382:microbiology*; D020869:Gene Expression Profiling; D006706:Homeostasis; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053474:Nod1 Signaling Adaptor Protein / Q000172:deficiency / Q000378:metabolism*; D053473:Nod2 Signaling Adaptor Protein / Q000172:deficiency / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction
chemical_list: D015415:Biomarkers; D053474:Nod1 Signaling Adaptor Protein; C507873:Nod1 protein, mouse; D053473:Nod2 Signaling Adaptor Protein; C495945:Nod2 protein, mouse
keywords: Nod-like receptors; gut bacterial communities; homeostasis; inflammation; intestinal environment
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