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Colitis susceptibility in p47(phox−/−) mice is mediated by the microbiome

BACKGROUND: Chronic granulomatous disease (CGD) is caused by defects in nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2) complex subunits (gp91(phox) (a.k.a. Nox2), p47(phox), p67(phox), p22(phox), p40(phox)) leading to reduced phagocyte-derived reactive oxygen species production. Almost...

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Autores principales: Falcone, E. Liana, Abusleme, Loreto, Swamydas, Muthulekha, Lionakis, Michail S., Ding, Li, Hsu, Amy P., Zelazny, Adrian M., Moutsopoulos, Niki M., Kuhns, Douglas B., Deming, Clay, Quiñones, Mariam, Segre, Julia A., Bryant, Clare E., Holland, Steven M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4820915/
https://www.ncbi.nlm.nih.gov/pubmed/27044504
http://dx.doi.org/10.1186/s40168-016-0159-0
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author Falcone, E. Liana
Abusleme, Loreto
Swamydas, Muthulekha
Lionakis, Michail S.
Ding, Li
Hsu, Amy P.
Zelazny, Adrian M.
Moutsopoulos, Niki M.
Kuhns, Douglas B.
Deming, Clay
Quiñones, Mariam
Segre, Julia A.
Bryant, Clare E.
Holland, Steven M.
author_facet Falcone, E. Liana
Abusleme, Loreto
Swamydas, Muthulekha
Lionakis, Michail S.
Ding, Li
Hsu, Amy P.
Zelazny, Adrian M.
Moutsopoulos, Niki M.
Kuhns, Douglas B.
Deming, Clay
Quiñones, Mariam
Segre, Julia A.
Bryant, Clare E.
Holland, Steven M.
author_sort Falcone, E. Liana
collection PubMed
description BACKGROUND: Chronic granulomatous disease (CGD) is caused by defects in nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2) complex subunits (gp91(phox) (a.k.a. Nox2), p47(phox), p67(phox), p22(phox), p40(phox)) leading to reduced phagocyte-derived reactive oxygen species production. Almost half of patients with CGD develop inflammatory bowel disease, and the involvement of the intestinal microbiome in relation to this predisposing immunodeficiency has not been explored. 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40168-016-0159-0) contains supplementary material, which is available to authorized users.
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spelling pubmed-48209152016-04-06 Colitis susceptibility in p47(phox−/−) mice is mediated by the microbiome Falcone, E. Liana Abusleme, Loreto Swamydas, Muthulekha Lionakis, Michail S. Ding, Li Hsu, Amy P. Zelazny, Adrian M. Moutsopoulos, Niki M. Kuhns, Douglas B. Deming, Clay Quiñones, Mariam Segre, Julia A. Bryant, Clare E. Holland, Steven M. Microbiome Research BACKGROUND: Chronic granulomatous disease (CGD) is caused by defects in nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2) complex subunits (gp91(phox) (a.k.a. Nox2), p47(phox), p67(phox), p22(phox), p40(phox)) leading to reduced phagocyte-derived reactive oxygen species production. Almost half of patients with CGD develop inflammatory bowel disease, and the involvement of the intestinal microbiome in relation to this predisposing immunodeficiency has not been explored. 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40168-016-0159-0) contains supplementary material, which is available to authorized users. BioMed Central 2016-04-05 /pmc/articles/PMC4820915/ /pubmed/27044504 http://dx.doi.org/10.1186/s40168-016-0159-0 Text en © Falcone et al. 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Falcone, E. Liana
Abusleme, Loreto
Swamydas, Muthulekha
Lionakis, Michail S.
Ding, Li
Hsu, Amy P.
Zelazny, Adrian M.
Moutsopoulos, Niki M.
Kuhns, Douglas B.
Deming, Clay
Quiñones, Mariam
Segre, Julia A.
Bryant, Clare E.
Holland, Steven M.
Colitis susceptibility in p47(phox−/−) mice is mediated by the microbiome
title Colitis susceptibility in p47(phox−/−) mice is mediated by the microbiome
title_full Colitis susceptibility in p47(phox−/−) mice is mediated by the microbiome
title_fullStr Colitis susceptibility in p47(phox−/−) mice is mediated by the microbiome
title_full_unstemmed Colitis susceptibility in p47(phox−/−) mice is mediated by the microbiome
title_short Colitis susceptibility in p47(phox−/−) mice is mediated by the microbiome
title_sort colitis susceptibility in p47(phox−/−) mice is mediated by the microbiome
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4820915/
https://www.ncbi.nlm.nih.gov/pubmed/27044504
http://dx.doi.org/10.1186/s40168-016-0159-0
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