title: Selective enrichment of commensal gut bacteria protects against Citrobacter rodentium-induced colitis.
abstract: The intestinal microbiota plays a key role in shaping the host immune system. Perturbation of gut microbial composition, termed dysbiosis, is associated with an increased susceptibility to intestinal pathogens and is a hallmark of a number of inflammatory, metabolic, and infectious diseases. The prospect of mining the commensal gut microbiota for bacterial strains that can impact immune function represents an attractive strategy to counteract dysbiosis and resulting disease. In this study, we show that selective enrichment of commensal gut lactobacilli protects against the murine pathogen Citrobacter rodentium, a well-characterized model of enteropathogenic and enterohemorrhagic Escherichia coli infection. The lactobacilli-enriched bacterial culture prevented the expansion of Gammaproteobacteria and Actinobacteria and was associated with improved indexes of epithelial barrier function (dextran flux), transmissible crypt hyperplasia, and tissue inflammatory cytokine levels. Moreover, cultivation of gut bacteria from Citrobacter rodentium-infected mice reveals the differential capacity of bacterial subsets to mobilize neutrophil oxidative burst and initiate the formation of weblike neutrophil extracellular traps. Our findings highlight the beneficial effects of a lactobacilli-enriched commensal gut microenvironment and, in the context of an intestinal barrier breach, the ability of neutrophils to immobilize both commensal and pathogenic bacteria.
authors.affiliation: Cell Biology Program, Research Institute, Division of Gastroenterology, Hepatology and Nutrition, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada; and.
authors.forename: Linda
authors.initials: L
authors.lastname: Vong
authors.affiliation: Cell Biology Program, Research Institute, Division of Gastroenterology, Hepatology and Nutrition, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada; and.
authors.forename: Lee J
authors.initials: LJ
authors.lastname: Pinnell
authors.affiliation: Cell Biology Program, Research Institute, Division of Gastroenterology, Hepatology and Nutrition, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada; and.
authors.forename: Pekka
authors.initials: P
authors.lastname: Määttänen
authors.affiliation: Cell Biology Program, Research Institute, Division of Gastroenterology, Hepatology and Nutrition, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada; and.
authors.forename: C William
authors.initials: CW
authors.lastname: Yeung
authors.affiliation: Cell Biology Program, Research Institute, Division of Gastroenterology, Hepatology and Nutrition, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada; and.
authors.forename: Eberhard
authors.initials: E
authors.lastname: Lurz
authors.affiliation: Cell Biology Program, Research Institute, Division of Gastroenterology, Hepatology and Nutrition, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada; and Faculty of Dentistry, University of Toronto, Toronto, Ontario, Canada philip.sherman@sickkids.ca.
authors.forename: Philip M
authors.initials: PM
authors.lastname: Sherman
mesh_terms: D039903:Actinobacteria / Q000502:physiology; D000818:Animals; D001431:Bacteriological Techniques; D044082:Citrobacter rodentium / Q000502:physiology*; D004195:Disease Models, Animal; D064806:Dysbiosis / Q000276:immunology / Q000517:prevention & control; D004756:Enterobacteriaceae Infections / Q000382:microbiology / Q000517:prevention & control; D020563:Gammaproteobacteria / Q000502:physiology; D054884:Host-Pathogen Interactions / Q000276:immunology; D007413:Intestinal Mucosa / Q000276:immunology*; D007778:Lactobacillus / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D056265:Microbial Interactions; D064307:Microbiota
keywords: Citrobacter rodentium; colitis; gut microbiota; lactobacilli; neutrophil extracellular traps