title: Adherent-invasive Escherichia coli Exacerbates Antibiotic-associated Intestinal Dysbiosis and Neutrophil Extracellular Trap Activation.
abstract: BACKGROUND
  Antibiotic-associated disruption of the gut microbiota is a known risk factor for Crohn's disease. This chronic inflammatory disorder results from aberrant host immune responses to subsets of the gut microbiota, and is characterized by intense neutrophil recruitment to the lamina propria, surface and crypt epithelium. Importantly, adherent-invasive Escherichia coli (AIEC) is abundant in ileal biopsies, highlighting a possible etiological role. In this study, we investigated the impact of antibiotics and AIEC challenge on murine intestinal dysbiosis and neutrophil extracellular trap activation, which is a critical component of the neutrophil antimicrobial repertoire.
  
  
  METHODS
  Male C57BL/6 mice were administered vancomycin and gentamicin (once daily, 3 days), and subsequently challenged with AIEC strain LF82 (once daily, 2 days). Perturbation of the gut microbiota was monitored using a combination of molecular and phylogenetic analyses. The impact of commensal and dysbiotic gut bacterial communities on neutrophil extracellular trap mobilization and intestinal redox balance was also quantified.
  
  
  RESULTS
  Exposure of neutrophils to murine commensal gut microbial communities activated neutrophil extracellular trap formation. The capacity of neutrophils to cast these web-like structures was exacerbated following antibiotic and AIEC-associated intestinal dysbiosis, highlighting the possible overgrowth of immune-activating intestinal pathobionts. Intestinal dysbiosis was associated with an elevated capacity of the cultivated gut bacteria to produce reactive oxygen species in vitro, and increased colonic oxidative stress in vivo.
  
  
  CONCLUSIONS
  Together, these data provide new insights into the detrimental effects of antibiotics on the gut microbiota, with clinically relevant implications for intestinal dysbiosis on neutrophil function and intestinal redox balance.
authors.affiliation: *Cell Biology Program, Research Institute, Division of Gastroenterology, Hepatology and Nutrition, Hospital for Sick Children, Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada; and †Faculty of Dentistry, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Linda
authors.initials: L
authors.lastname: Vong
authors.forename: Chiu W
authors.initials: CW
authors.lastname: Yeung
authors.forename: Lee J
authors.initials: LJ
authors.lastname: Pinnell
authors.forename: Philip M
authors.initials: PM
authors.lastname: Sherman
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001422:Bacterial Adhesion; D064806:Dysbiosis / Q000188:drug therapy / Q000209:etiology* / Q000473:pathology; D004926:Escherichia coli / Q000472:pathogenicity*; D004927:Escherichia coli Infections / Q000188:drug therapy / Q000209:etiology* / Q000473:pathology; D065206:Extracellular Traps / Q000187:drug effects / Q000276:immunology* / Q000382:microbiology; D007413:Intestinal Mucosa / Q000187:drug effects / Q000382:microbiology* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology* / Q000382:microbiology / Q000473:pathology
chemical_list: D000900:Anti-Bacterial Agents