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Humanized microbiota mice as a model of recurrent Clostridium difficile disease

BACKGROUND: Clostridium difficile disease is the leading antibiotic-associated cause of diarrhea and nosocomial acquired infection in the western world. The per annum burden in the USA alone amounts to 250,000 cases with 14,000 ascribed deaths and medical costs in excess of a billion dollars. Novel...

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Autores principales: Collins, James, Auchtung, Jennifer M., Schaefer, Laura, Eaton, Kathryn A., Britton, Robert A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4546040/
https://www.ncbi.nlm.nih.gov/pubmed/26289776
http://dx.doi.org/10.1186/s40168-015-0097-2
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author Collins, James
Auchtung, Jennifer M.
Schaefer, Laura
Eaton, Kathryn A.
Britton, Robert A.
author_facet Collins, James
Auchtung, Jennifer M.
Schaefer, Laura
Eaton, Kathryn A.
Britton, Robert A.
author_sort Collins, James
collection PubMed
description BACKGROUND: Clostridium difficile disease is the leading antibiotic-associated cause of diarrhea and nosocomial acquired infection in the western world. The per annum burden in the USA alone amounts to 250,000 cases with 14,000 ascribed deaths and medical costs in excess of a billion dollars. Novel models for the study of C. difficile infection are therefore pertinent. RESULTS: Germ free C57BL/6 mice gavaged with a healthy human fecal microbiota maintained a stable “humanized” microbiota over multiple generations when housed under specific pathogen-free (SPF) conditions. As with mice containing a conventional microbiota, treatment with a five-antibiotic cocktail followed by a single dose of clindamycin renders the animals susceptible to C. difficile infection (CDI). Interestingly, after recovery from the initial CDI infection, a single intraperitoneal injection of clindamycin is sufficient to induce CDI relapse. Relapse of CDI can be induced up to 35 days postinfection after recovery from the initial infection, and multiple episodes of relapse can be induced. CONCLUSIONS: This model enables the study of recurrent C. difficile disease in a host containing a human-derived microbiota. Probiotic treatments using human-derived microbes, either prophylactic or curative, can be tested within the model. The identification and testing of human-derived microbial communities within a humanized microbiota mouse model may enable a higher rate of successful transfer of bacteria-based treatments from the lab to human patients due to the microbes involved initiating from, and being adapted to, the human GI tract. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40168-015-0097-2) contains supplementary material, which is available to authorized users.
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spelling pubmed-45460402015-08-23 Humanized microbiota mice as a model of recurrent Clostridium difficile disease Collins, James Auchtung, Jennifer M. Schaefer, Laura Eaton, Kathryn A. Britton, Robert A. Microbiome Research BACKGROUND: Clostridium difficile disease is the leading antibiotic-associated cause of diarrhea and nosocomial acquired infection in the western world. The per annum burden in the USA alone amounts to 250,000 cases with 14,000 ascribed deaths and medical costs in excess of a billion dollars. Novel models for the study of C. difficile infection are therefore pertinent. RESULTS: Germ free C57BL/6 mice gavaged with a healthy human fecal microbiota maintained a stable “humanized” microbiota over multiple generations when housed under specific pathogen-free (SPF) conditions. As with mice containing a conventional microbiota, treatment with a five-antibiotic cocktail followed by a single dose of clindamycin renders the animals susceptible to C. difficile infection (CDI). Interestingly, after recovery from the initial CDI infection, a single intraperitoneal injection of clindamycin is sufficient to induce CDI relapse. Relapse of CDI can be induced up to 35 days postinfection after recovery from the initial infection, and multiple episodes of relapse can be induced. CONCLUSIONS: This model enables the study of recurrent C. difficile disease in a host containing a human-derived microbiota. Probiotic treatments using human-derived microbes, either prophylactic or curative, can be tested within the model. The identification and testing of human-derived microbial communities within a humanized microbiota mouse model may enable a higher rate of successful transfer of bacteria-based treatments from the lab to human patients due to the microbes involved initiating from, and being adapted to, the human GI tract. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40168-015-0097-2) contains supplementary material, which is available to authorized users. BioMed Central 2015-08-20 /pmc/articles/PMC4546040/ /pubmed/26289776 http://dx.doi.org/10.1186/s40168-015-0097-2 Text en © Collins et al. 2015 Open Access This 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
Collins, James
Auchtung, Jennifer M.
Schaefer, Laura
Eaton, Kathryn A.
Britton, Robert A.
Humanized microbiota mice as a model of recurrent Clostridium difficile disease
title Humanized microbiota mice as a model of recurrent Clostridium difficile disease
title_full Humanized microbiota mice as a model of recurrent Clostridium difficile disease
title_fullStr Humanized microbiota mice as a model of recurrent Clostridium difficile disease
title_full_unstemmed Humanized microbiota mice as a model of recurrent Clostridium difficile disease
title_short Humanized microbiota mice as a model of recurrent Clostridium difficile disease
title_sort humanized microbiota mice as a model of recurrent clostridium difficile disease
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4546040/
https://www.ncbi.nlm.nih.gov/pubmed/26289776
http://dx.doi.org/10.1186/s40168-015-0097-2
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