Defined Nutrient Diets Alter Susceptibility to Clostridium difficile Associated Disease in a Murine Model

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 t...

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Bibliographic Details
Published in:PloS one 2015-07, Vol.10 (7), p.e0131829-e0131829
Main Authors: 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
Format: Article
Language:English
Subjects:
Animal models
Animals
Anti-Bacterial Agents - pharmacology
Antibiotics
Antimicrobial agents
Bacteria
Bacterial Load
Body weight loss
Cecum
Cecum - microbiology
Clostridioides difficile
Clostridium difficile
Colonization
Diarrhea
Diet
Diet, Protein-Restricted
Disease Susceptibility
Enterocolitis, Pseudomembranous - microbiology
Gastrointestinal Microbiome - drug effects
Gastrointestinal Microbiome - genetics
Health aspects
Hospitals
Infection
Infections
Infectious diseases
Inflammatory bowel disease
Ingredients
Inoculation
Intestinal microflora
Intestine
Low protein diet
Male
Malnutrition
Mice
Mice, Inbred C57BL
Microbiota
Microbiota (Symbiotic organisms)
Mortality
Nutrient deficiency
Nutrients
Nutrition research
Nutritional status
Pathogens
Protective Factors
Protein Deficiency - microbiology
Proteins
Rodents
Shedding
Studies
Survival
Tropical diseases
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Summary: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. 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. 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. 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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0131829