Objectives: C. 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% Fe3+ saturated) bovine apo-lactoferrin (apo-bLf) and iron-saturated (85% Fe3+ 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 (5mg/mL, once daily) for 35 days. After 7 days, clindamycin was instilled (33.9mg/L, four times daily) to induce simulated CDI. Indigenous microflora populations, C. difficile total counts and spores , cytotoxin titres, short-chain fatty acids, biometals, lactoferrin, and iron content of lactoferrin were monitored daily. Results: In the apo-bLf model, germination of C. difficile spores occurred 6 days post-clindamycin, followed by rapid vegetative cell proliferation and detectable toxin. By contrast, in the holo-bLf model, only a modest vegetative cell population was observed until 16 days post-antibiotic. 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.
CORE (COnnecting REpositories)
CORE (COnnecting REpositories)