Abstract
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.MethodsC57BL/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.ConclusionsLow 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.
Highlights
Clostridium difficile is an anaerobic, spore-forming, gram-positive bacterium [1] that causes disease mainly through the activity of two toxins, TcdA and TcdB
Select intestinal microbiota were measured in stool and C. difficilegrowth and toxin production were quantified ex vivoin intestinal contents from untreated or antibiotic-treated mice fed with the different diets
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
Summary
Clostridium difficile is an anaerobic, spore-forming, gram-positive bacterium [1] that causes disease mainly through the activity of two toxins, TcdA and TcdB. C. difficile is recognized as the major identifiable and treatable causative agent of antibiotic-associated diarrhea[3]. C. difficile infection (CDI) has a wide clinical range from asymptomatic carriage to mild self-limiting diarrhea to severe pseudomembranous colitis (PMC) [4]. With the emergence of hypervirulent strains and increased use of antibiotics incidence of CDI has dramatically increased during recent years. Studies performed in Canada, USA and Europe report increases as much as two to four fold in CDI incidence in the past decade [5, 6]. Clostridium difficile is a major identifiable and treatable cause of antibiotic-associated diarrhea. 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
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