title: Potential of lactoferrin to prevent antibiotic-induced Clostridium difficile infection.
abstract: OBJECTIVE
  Clostridium difficile infection (CDI) is a global healthcare problem. Recent evidence suggests that the availability of iron may be important for C. difficile growth. This study evaluated the comparative effects of iron-depleted (1% Fe(3+) saturated) bovine apo-lactoferrin (apo-bLf) and iron-saturated (85% Fe(3+) saturated) bovine holo-lactoferrin (holo-bLf) in a human in vitro gut model that simulates CDI.
  
  
  METHODS
  Two parallel triple-stage chemostat gut models were inoculated with pooled human faeces and spiked with C. difficile spores (strain 027 210, PCR ribotype 027). Holo- or apo-bLf was instilled (5 mg/mL, once daily) for 35 days. After 7 days, clindamycin was instilled (33.9 mg/L, four times daily) to induce simulated CDI. Indigenous microflora populations, C. difficile total counts and spores, cytotoxin titres, short chain fatty acid concentrations, biometal concentrations, lactoferrin concentration and iron content of lactoferrin were monitored daily.
  
  
  RESULTS
  In the apo-bLf model, germination of C. difficile spores occurred 6 days post instillation of clindamycin, followed by rapid vegetative cell proliferation and detectable toxin production. By contrast, in the holo-bLf model, only a modest vegetative cell population was observed until 16 days post antibiotic administration. Notably, no toxin was detected in this model. In separate batch culture experiments, holo-bLf prevented C. difficile vegetative cell growth and toxin production, whereas apo-bLf and iron alone did not.
  
  
  CONCLUSIONS
  Holo-bLf, but not apo-bLf, delayed C. difficile growth and prevented toxin production in a human gut model of CDI. This inhibitory effect may be iron independent. These observations suggest that bLf in its iron-saturated state could be used as a novel preventative or treatment strategy for CDI.
authors.affiliation: Leeds Institute for Molecular Medicine, University of Leeds, Leeds, UK.
authors.forename: C H
authors.initials: CH
authors.lastname: Chilton
authors.affiliation: Leeds Institute for Molecular Medicine, University of Leeds, Leeds, UK.
authors.forename: G S
authors.initials: GS
authors.lastname: Crowther
authors.affiliation: Department of Inorganic Chemistry, Jagiellonian University, Krakow, Poland.
authors.forename: K
authors.initials: K
authors.lastname: Śpiewak
authors.affiliation: Department of Inorganic Chemistry, Jagiellonian University, Krakow, Poland.
authors.forename: M
authors.initials: M
authors.lastname: Brindell
authors.affiliation: NIHR Biomedical Research Unit in Gastrointestinal and Liver Diseases at Nottingham University Hospitals NHS Trust and The University of Nottingham, Nottingham, UK.
authors.forename: G
authors.initials: G
authors.lastname: Singh
authors.affiliation: Leeds Institute for Molecular Medicine, University of Leeds, Leeds, UK.
authors.forename: M H
authors.initials: MH
authors.lastname: Wilcox
authors.affiliation: NIHR Biomedical Research Unit in Gastrointestinal and Liver Diseases at Nottingham University Hospitals NHS Trust and The University of Nottingham, Nottingham, UK tanya.monaghan@nottingham.ac.uk.
authors.forename: T M
authors.initials: TM
authors.lastname: Monaghan
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use*; D058491:Bacterial Load; D002981:Clindamycin / Q000494:pharmacology; D016360:Clostridioides difficile / Q000187:drug effects*; D003015:Clostridium Infections / Q000517:prevention & control*; D004761:Enterocolitis, Pseudomembranous / Q000517:prevention & control*; D005243:Feces / Q000382:microbiology; D041981:Gastrointestinal Tract / Q000187:drug effects / Q000382:microbiology; D006801:Humans; D007422:Intestines / Q000187:drug effects / Q000382:microbiology; D007501:Iron / Q000737:chemistry; D007781:Lactoferrin / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D013171:Spores, Bacterial / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D002981:Clindamycin; D007501:Iron; D007781:Lactoferrin