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
Citation
Brugman, S., Liu, K.Y., Lindenbergh-Kortleve, D., Samsom, J.N., Furuta, G.T., Renshaw, S.A., Willemsen, R., and Nieuwenhuis, E.E. (2009) Oxazolone-induced enterocolitis in zebrafish depends on the composition of the intestinal microbiota. Gastroenterology. 137(5):1757.e1-1767.e1.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping