PUBLICATION

Oxazolone-induced enterocolitis in zebrafish depends on the composition of the intestinal microbiota

Authors
Brugman, S., Liu, K.Y., Lindenbergh-Kortleve, D., Samsom, J.N., Furuta, G.T., Renshaw, S.A., Willemsen, R., and Nieuwenhuis, E.E.
ID
ZDB-PUB-090828-11
Date
2009
Source
Gastroenterology   137(5): 1757.e1-1767.e1 (Journal)
Registered Authors
Renshaw, Steve A.
Keywords
none
MeSH Terms
  • Adjuvants, Immunologic*/pharmacology
  • Animals
  • Anti-Bacterial Agents/therapeutic use
  • Colistin/therapeutic use
  • Disease Models, Animal
  • Enterocolitis/drug therapy
  • Enterocolitis/microbiology*
  • Enterocolitis/pathology*
  • Intestines/drug effects
  • Intestines/microbiology*
  • Intestines/pathology
  • Oxazolone*/pharmacology
  • Vancomycin/therapeutic use
  • Zebrafish
PubMed
19698716 Full text @ Gastroenterology
Abstract
BACKGROUND & AIMS:: The pathogenesis of inflammatory bowel disease involves dysfunctional mucosal immune responses to commensal bacteria in genetically predisposed hosts. The interactions between host cells and bacteria are complicated, making it a challenge to assess their relative contribution to intestinal pathology. We developed a zebrafish model of enterocolitis to study these interactions. METHODS:: Enterocolitis was induced by intra-rectal administration of the hapten oxazolone in adult wild-type and myeloperoxidase-reporter transgenic zebrafish in the presence or absence of antibiotics. Intestinal inflammation was evaluated by histological and flow cytometry analyses and cytokine profiling with quantitative real-time PCR. Changes in the composition of the intestinal microbiota following antibiotic administration were assessed by 16SrRNA sequencing; bacterial load was quantified by culture on non-selective media (CFU). RESULTS:: In zebrafish, the infiltrate and severity of oxazolone-induced enterocolitis are influenced by the composition of the microbiota. Inflammation is characterized by granulocyte influx; epithelial damage; goblet-cell depletion; and increased expression of interleukin (IL)-1beta, tumor necrosis factor (TNF)a, and IL-10. Zebrafish given vancomycin had bacterial populations dominated by Fusobacteria and reduced enterocolitis scores, intestinal damage, and percentages of infiltrating neutrophils and eosinophils. In contrast, zebrafish given colistin sulphate had a predominance of Proteobacteria and reduced eosinophil and lymphocyte infiltration, but enterocolitis scores were not reduced. CONCLUSION:: In zebrafish with oxazolone-induced enterocolitis, components of the intestinal microbiota affect the severity and composition of the intestinal infiltrate.
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