Potential of lactoferrin to prevent antibiotic-inducedClostridium difficileinfection

Abstract

ObjectivesClostridium 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.MethodsTwo 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.ResultsIn 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.ConclusionsHolo-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.

Sleeping with the enemy: Clostridium difficile infection in the intensive care unit

“…Other groups have begun to examine the effects of a purposeful colonization of the colon with nonpathogenic strains of C. difficile [ 77 ]. Iron-saturated bovine lactoferrin has been shown to delay C. difficile growth and toxin production in vitro [ 78 ]. These potential new tools in our preventative armamentarium are still far from routine clinical use, and none have been evaluated in the ICU setting.…”

Inhibiting Growth of Clostridioides difficile by Restoring Valerate, Produced by the Intestinal Microbiota

“…Chemostats have previously been used to model CDI and test the effects of several treatments on C difficile growth and pathogenesis (e.g. antibiotics,16–19 bacteriophages,20 and lactoferrin21).…”

<p>Recent advances in the treatment of <em>C. difficile</em> using biotherapeutic agents</p>

“…The PaLoc locus also contains 3 accessory genes tcdC (negatively regulates tcdA and tcdB ) tcdE (encodes a putative holing necessary for toxin release) and tcdR (RNA polymerase sigma factor). The roles of tcdC and tcdE remain controversial as toxin production barely differs between tcdC mutant and wild type strains, whilst reports suggest tcdE holio protein may play a role in toxin release 42. Furthermore, several studies show tcdC expression levels do not diminish during the stationary phase of growth, suggesting that tcdC may adopt a modulatory role rather than a repressive one.…”