title: Resilience of the intestinal microbiota following pathogenic bacterial infection is independent of innate immunity mediated by NOD1 or NOD2.
abstract: The innate immune receptors, NOD1 and NOD2, are key regulators of intestinal homeostasis. NOD2 deficiency is linked to increased risk for Crohn's disease, a type of inflammatory bowel disease characterized by chronic inflammatory pathology and dysbiosis within resident microbial communities. However, the relationship between NOD protein-regulated immune functions and dysbiosis remains unclear. We hypothesized that the relationship between NOD1 or NOD2 deficiency and altered community structure during chronic disease may arise via NOD-dependent impairment of community resilience over time. Using the Salmonella ΔaroA model of chronic colitis with littermate mice to control for environmental influences on the microbiota, we show that NOD proteins exert a relatively minor impact on the chronic inflammatory environment and do not significantly contribute to bacterial abundance or community resilience following infection. Rather, temporal shifts in relative abundance of targeted bacterial groups correlated with inflammatory phenotype driven by presence of the pathogen and the ensuing complex immune response.
authors.affiliation: Department of Immunology, University of Toronto, Toronto, Ontario, M5S 1A8, Canada.
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Robertson
authors.affiliation: Department of Immunology, University of Toronto, Toronto, Ontario, M5S 1A8, Canada.
authors.forename: Kaoru
authors.initials: K
authors.lastname: Geddes
authors.affiliation: Department of Immunology, University of Toronto, Toronto, Ontario, M5S 1A8, Canada.
authors.forename: Charles
authors.initials: C
authors.lastname: Maisonneuve
authors.affiliation: Surgical Pathology, Department of Pathology and Laboratory Medicine, St. Michael's Hospital, Toronto, Ontario, M5B 1W8, Canada.
authors.forename: Catherine J
authors.initials: CJ
authors.lastname: Streutker
authors.affiliation: Department of Immunology, University of Toronto, Toronto, Ontario, M5S 1A8, Canada. Electronic address: dana.philpott@utoronto.ca.
authors.forename: Dana J
authors.initials: DJ
authors.lastname: Philpott
mesh_terms: D000818:Animals; D003092:Colitis / Q000276:immunology; D004195:Disease Models, Animal; D064806:Dysbiosis; D000069196:Gastrointestinal Microbiome; D007113:Immunity, Innate; D008810:Mice, Inbred C57BL; D053474:Nod1 Signaling Adaptor Protein / Q000378:metabolism*; D053473:Nod2 Signaling Adaptor Protein / Q000378:metabolism*; D012481:Salmonella Infections, Animal / Q000276:immunology*
chemical_list: D053474:Nod1 Signaling Adaptor Protein; C507873:Nod1 protein, mouse; D053473:Nod2 Signaling Adaptor Protein; C495945:Nod2 protein, mouse
keywords: Bacterial community structure; Chronic colitis model; Innate receptors; NOD proteins; Salmonella ΔaroA; Temporal dynamics