<i>Firmicutes</i> to <i>Bacteroidetes</i> ratio.

<p><i>Firmicutes</i> to <i>Bacteroidetes</i> ratio in the colon contents (lumen) was significantly higher (ANOVA p = 0.0021, post-tests both p<0.01) in the traditional diet fed group treated with antibiotics compared with either defined nutrient diet with antibiotics.</p

Treatment schedule for mice for the <i>in vivo</i> infection model (A) and <i>ex vivo C</i>. <i>difficile</i> inoculation studies (B).

<p>Treatment schedule for mice for the <i>in vivo</i> infection model (A) and <i>ex vivo C</i>. <i>difficile</i> inoculation studies (B).</p

Effects of nutritional status and diets on mortality, disease severity and infection burden in mice challenged with <i>C</i>. <i>difficile</i>.

<p>Effects of nutritional status and diets on mortality, disease severity and infection burden in mice challenged with <i>C</i>. <i>difficile</i>.</p

Defined Nutrient Diets Alter Susceptibility to <i>Clostridium difficile</i> Associated Disease in a Murine Model

<div><p>Background</p><p><i>Clostridium difficile</i> 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 <i>C</i>. <i>difficile</i> infection in a murine model.</p><p>Methods</p><p>C57BL/6 mice were fed a traditional house chow or a defined diet with either 20% protein or 2% protein and infected with <i>C</i>. <i>difficile</i> strain VPI10463. Animals were monitored for disease severity, clostridial shedding and fecal toxin levels. Select intestinal microbiota were measured in stool and <i>C</i>. <i>difficile </i>growth and toxin production were quantified <i>ex vivo </i>in intestinal contents from untreated or antibiotic-treated mice fed with the different diets.</p><p>Results</p><p><i>C</i>. <i>difficile </i>infected mice fed with defined diets, particularly (and unexpectedly) with protein deficient diet, had increased survival, decreased weight loss, and decreased overall disease severity. <i>C</i>. <i>difficile</i> 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. <i>Ex vivo</i> inoculation of cecal contents from antibiotic-treated mice showed decreased toxin production and <i>C</i>. <i>difficile</i> growth in both defined diets compared with a traditional diet.</p><p>Conclusions</p><p>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.</p></div