title: Defined Nutrient Diets Alter Susceptibility to Clostridium difficile Associated Disease in a Murine Model.
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.
  
  
  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.
authors.affiliation: Division of Infectious Diseases and International Health, University of Virginia, Charlottesville, Virginia, United States of America.
authors.forename: John H
authors.initials: JH
authors.lastname: Moore
authors.affiliation: Biomedicine Institute, Federal University of Ceará, Fortaleza, Brazil.
authors.forename: Caio C D
authors.initials: CC
authors.lastname: Pinheiro
authors.affiliation: Division of Infectious Diseases and International Health, University of Virginia, Charlottesville, Virginia, United States of America.
authors.forename: Edna I
authors.initials: EI
authors.lastname: Zaenker
authors.affiliation: Division of Infectious Diseases and International Health, University of Virginia, Charlottesville, Virginia, United States of America.
authors.forename: David T
authors.initials: DT
authors.lastname: Bolick
authors.affiliation: Division of Infectious Diseases and International Health, University of Virginia, Charlottesville, Virginia, United States of America.
authors.forename: Glynis L
authors.initials: GL
authors.lastname: Kolling
authors.affiliation: Division of Infectious Diseases and International Health, University of Virginia, Charlottesville, Virginia, United States of America.
authors.forename: Edward
authors.initials: E
authors.lastname: van Opstal
authors.affiliation: Biomedicine Institute, Federal University of Ceará, Fortaleza, Brazil.
authors.forename: Francisco J D
authors.initials: FJ
authors.lastname: Noronha
authors.affiliation: Biomedicine Institute, Federal University of Ceará, Fortaleza, Brazil.
authors.forename: Pedro H Q S
authors.initials: PH
authors.lastname: De Medeiros
authors.affiliation: Biomedicine Institute, Federal University of Ceará, Fortaleza, Brazil.
authors.forename: Raphael S
authors.initials: RS
authors.lastname: Rodriguez
authors.affiliation: Biomedicine Institute, Federal University of Ceará, Fortaleza, Brazil.
authors.forename: Aldo A
authors.initials: AA
authors.lastname: Lima
authors.affiliation: Division of Infectious Diseases and International Health, University of Virginia, Charlottesville, Virginia, United States of America.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Guerrant
authors.affiliation: Division of Infectious Diseases and International Health, University of Virginia, Charlottesville, Virginia, United States of America.
authors.forename: Cirle A
authors.initials: CA
authors.lastname: Warren
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D058491:Bacterial Load; D002432:Cecum / Q000382:microbiology; D016360:Clostridioides difficile; D018753:Diet, Protein-Restricted; D004198:Disease Susceptibility; D004761:Enterocolitis, Pseudomembranous / Q000382:microbiology*; D000069196:Gastrointestinal Microbiome / Q000187:drug effects / Q000235:genetics; D008297:Male; D008810:Mice, Inbred C57BL; D065840:Protective Factors; D011488:Protein Deficiency / Q000382:microbiology
chemical_list: D000900:Anti-Bacterial Agents