Abstract | BACKGROUND: RESULTS: Although CGD mice do not spontaneously develop colitis, we demonstrate that p47( phox-/-) mice have increased susceptibility to dextran sodium sulfate colitis in association with a distinct colonic transcript and microbiome signature. Neither restoring NOX2 reactive oxygen species production nor normalizing the microbiome using cohoused adult p47( phox-/-) with B6Tac (wild type) mice reversed this phenotype. However, breeding p47( phox+/-) mice and standardizing the microflora between littermate p47( phox-/-) and B6Tac mice from birth significantly reduced dextran sodium sulfate colitis susceptibility in p47( phox-/-) mice. We found similarly decreased colitis susceptibility in littermate p47( phox-/-) and B6Tac mice treated with Citrobacter rodentium. CONCLUSIONS: Our findings suggest that the microbiome signature established at birth may play a bigger role than phagocyte-derived reactive oxygen species in mediating colitis susceptibility in CGD mice. These data further support bacteria-related disease in CGD colitis.
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Authors | E Liana Falcone, Loreto Abusleme, Muthulekha Swamydas, Michail S Lionakis, Li Ding, Amy P Hsu, Adrian M Zelazny, Niki M Moutsopoulos, Douglas B Kuhns, Clay Deming, Mariam Quiñones, Julia A Segre, Clare E Bryant, Steven M Holland |
Journal | Microbiome
(Microbiome)
Vol. 4
Pg. 13
(Apr 05 2016)
ISSN: 2049-2618 [Electronic] England |
PMID | 27044504
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural)
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Chemical References |
- Reactive Oxygen Species
- NADP
- Dextran Sulfate
- NADPH Oxidases
- neutrophil cytosolic factor 1
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Topics |
- Adult
- Animals
- Citrobacter rodentium
(pathogenicity, physiology)
- Colitis
(chemically induced, genetics, microbiology, pathology)
- Crosses, Genetic
- Dextran Sulfate
- Disease Models, Animal
- Disease Susceptibility
- Female
- Gene Expression
- Granulomatous Disease, Chronic
(genetics, microbiology, pathology)
- Humans
- Inflammatory Bowel Diseases
(chemically induced, genetics, microbiology, pathology)
- Mice
- Mice, Knockout
- Microbiota
(genetics)
- NADP
(metabolism)
- NADPH Oxidases
(deficiency, genetics)
- Reactive Oxygen Species
(metabolism)
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