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Defined Nutrient Diets Alter Susceptibility to Clostridium difficile Associated Disease in a Murine Model
BACKGROUND: Clostridium difficile is a major identifiable and treatable cause of antibiotic-associated diarrhea. Poor nutritional status contributes to mortality through weakened host defenses against various pathogens. The primary goal of this study was to assess the contribution of a reduced prote...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4504475/ https://www.ncbi.nlm.nih.gov/pubmed/26181795 http://dx.doi.org/10.1371/journal.pone.0131829 |
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author | Moore, John H. Pinheiro, Caio C. D. Zaenker, Edna I. Bolick, David T. Kolling, Glynis L. van Opstal, Edward Noronha, Francisco J. D. De Medeiros, Pedro H. Q. S. Rodriguez, Raphael S. Lima, Aldo A. Guerrant, Richard L. Warren, Cirle A. |
author_facet | Moore, John H. Pinheiro, Caio C. D. Zaenker, Edna I. Bolick, David T. Kolling, Glynis L. van Opstal, Edward Noronha, Francisco J. D. De Medeiros, Pedro H. Q. S. Rodriguez, Raphael S. Lima, Aldo A. Guerrant, Richard L. Warren, Cirle A. |
author_sort | Moore, John H. |
collection | PubMed |
description | BACKGROUND: Clostridium difficile is a major identifiable and treatable cause of antibiotic-associated diarrhea. Poor nutritional status contributes to mortality through weakened host defenses against various pathogens. The primary goal of this study was to assess the contribution of a reduced protein diet to the outcomes of C. difficile infection in a murine model. METHODS: C57BL/6 mice were fed a traditional house chow or a defined diet with either 20% protein or 2% protein and infected with C. difficile strain VPI10463. Animals were monitored for disease severity, clostridial shedding and fecal toxin levels. Select intestinal microbiota were measured in stool and C. difficile growth and toxin production were quantified ex vivo in intestinal contents from untreated or antibiotic-treated mice fed with the different diets. RESULTS: C. difficile infected mice fed with defined diets, particularly (and unexpectedly) with protein deficient diet, had increased survival, decreased weight loss, and decreased overall disease severity. C. difficile shedding and toxin in the stool of the traditional diet group was increased compared with either defined diet 1 day post infection. Mice fed with traditional diet had an increased intestinal Firmicutes to Bacteroidetes ratio following antibiotic exposure compared with either a 2% or 20% protein defined nutrient diet. Ex vivo inoculation of cecal contents from antibiotic-treated mice showed decreased toxin production and C. difficile growth in both defined diets compared with a traditional diet. CONCLUSIONS: Low protein diets, and defined nutrient diets in general, were found to be protective against CDI in mice. Associated diet-induced alterations in intestinal microbiota may influence colonization resistance and clostridial toxin production in a defined nutrient diet compared to a traditional diet, leading to increased survival. However, mechanisms which led to survival differences between 2% and 20% protein defined nutrient diets need to be further elucidated. |
format | Online Article Text |
id | pubmed-4504475 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-45044752015-07-17 Defined Nutrient Diets Alter Susceptibility to Clostridium difficile Associated Disease in a Murine Model Moore, John H. Pinheiro, Caio C. D. Zaenker, Edna I. Bolick, David T. Kolling, Glynis L. van Opstal, Edward Noronha, Francisco J. D. De Medeiros, Pedro H. Q. S. Rodriguez, Raphael S. Lima, Aldo A. Guerrant, Richard L. Warren, Cirle A. PLoS One Research Article BACKGROUND: Clostridium difficile is a major identifiable and treatable cause of antibiotic-associated diarrhea. Poor nutritional status contributes to mortality through weakened host defenses against various pathogens. The primary goal of this study was to assess the contribution of a reduced protein diet to the outcomes of C. difficile infection in a murine model. METHODS: C57BL/6 mice were fed a traditional house chow or a defined diet with either 20% protein or 2% protein and infected with C. difficile strain VPI10463. Animals were monitored for disease severity, clostridial shedding and fecal toxin levels. Select intestinal microbiota were measured in stool and C. difficile growth and toxin production were quantified ex vivo in intestinal contents from untreated or antibiotic-treated mice fed with the different diets. RESULTS: C. difficile infected mice fed with defined diets, particularly (and unexpectedly) with protein deficient diet, had increased survival, decreased weight loss, and decreased overall disease severity. C. difficile shedding and toxin in the stool of the traditional diet group was increased compared with either defined diet 1 day post infection. Mice fed with traditional diet had an increased intestinal Firmicutes to Bacteroidetes ratio following antibiotic exposure compared with either a 2% or 20% protein defined nutrient diet. Ex vivo inoculation of cecal contents from antibiotic-treated mice showed decreased toxin production and C. difficile growth in both defined diets compared with a traditional diet. CONCLUSIONS: Low protein diets, and defined nutrient diets in general, were found to be protective against CDI in mice. Associated diet-induced alterations in intestinal microbiota may influence colonization resistance and clostridial toxin production in a defined nutrient diet compared to a traditional diet, leading to increased survival. However, mechanisms which led to survival differences between 2% and 20% protein defined nutrient diets need to be further elucidated. Public Library of Science 2015-07-16 /pmc/articles/PMC4504475/ /pubmed/26181795 http://dx.doi.org/10.1371/journal.pone.0131829 Text en © 2015 Moore et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Moore, John H. Pinheiro, Caio C. D. Zaenker, Edna I. Bolick, David T. Kolling, Glynis L. van Opstal, Edward Noronha, Francisco J. D. De Medeiros, Pedro H. Q. S. Rodriguez, Raphael S. Lima, Aldo A. Guerrant, Richard L. Warren, Cirle A. Defined Nutrient Diets Alter Susceptibility to Clostridium difficile Associated Disease in a Murine Model |
title | Defined Nutrient Diets Alter Susceptibility to Clostridium difficile Associated Disease in a Murine Model |
title_full | Defined Nutrient Diets Alter Susceptibility to Clostridium difficile Associated Disease in a Murine Model |
title_fullStr | Defined Nutrient Diets Alter Susceptibility to Clostridium difficile Associated Disease in a Murine Model |
title_full_unstemmed | Defined Nutrient Diets Alter Susceptibility to Clostridium difficile Associated Disease in a Murine Model |
title_short | Defined Nutrient Diets Alter Susceptibility to Clostridium difficile Associated Disease in a Murine Model |
title_sort | defined nutrient diets alter susceptibility to clostridium difficile associated disease in a murine model |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4504475/ https://www.ncbi.nlm.nih.gov/pubmed/26181795 http://dx.doi.org/10.1371/journal.pone.0131829 |
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