Characterization of Chicken IgY Specific to Clostridium difficile R20291 Spores and the Effect of Oral Administration in Mouse Models of Initiation and Recurrent Disease

Abstract

Clostridium difficile infection (CDI) are the leading cause of world-wide nosocomial acquired diarrhea. The current main clinical challenge in CDI is the elevated rate of infection recurrence that may reach up to 30% of the patients, which has been associated to the formation of dormant spores during the infection. We sought to characterize the effects of oral administration of specific anti-spore IgY in mouse models of CDI and recurrent CDI. The specificity of anti-spore IgY was evaluated in vitro. In both, initiation mouse model and recurrence mouse model, we evaluated the prophylactic and therapeutic effect of anti-spore IgY, respectively. Our results demonstrate that anti-spore IgY exhibited high specificity and titers against C. difficile spores and reduced spore adherence to intestinal cells in vitro. Administration of anti-spore IgY to C57BL/6 mice prior and during CDI delayed the appearance of the diarrhea by 1.5 day, and spore adherence to the colonic mucosa by 90%. Notably, in the recurrence model, co-administration of anti-spore IgY coupled with vancomycin delayed the appearance of recurrent diarrhea by a median of 2 days. Collectively, these observations suggest that anti-spore IgY antibodies may be used as a novel prophylactic treatment for CDI, or in combination with antibiotics to treat CDI and prevent recurrence of the infection.

Lauric Acid Is an Inhibitor of Clostridium difficile Growth in Vitro and Reduces Inflammation in a Mouse Infection Model

“…All animal studies were performed following the protocol approved by the IACUC of NCKU (approval NCKU-IACUC-102-149) and the Biosafety and Radiation Safety Management Division of NCKU. The animal model of CDI was established as previously described ( Chen et al, 2008 ; Liu et al, 2017 ; Pizarro-Guajardo et al, 2017 ). Five animals were administered 12 mg/kg (low dose) and 24 mg/kg (high dose) of lauric acid dissolved in PBS orogastrically once per day for 7 days prior to infection with C. difficile and once more 1 day following infection.…”

Egg yolk antibodies (IgY) and their applications in human and veterinary health: A review

“…Oral administration of IgY against Clostridium difficile spores both delayed the onset of diarrhea in rats treated prior to the infection and reduced its recurrence in infected rats. Thus, specific IgY could be used in the prophylaxis of C. difficile infection, as well as an immunotherapeutic to eliminate the remaining spores on the intestines of people who have already had the infection, which would reduce the recurrence of diarrhea [61].…”

Therapeutic administration of the recombinant antimicrobial peptide microcin J25 effectively enhances host defenses against gut inflammation and epithelial barrier injury induced by enterotoxigenic Escherichia coli infection

“…For disease activity evaluation, the clinical condition of the mice was monitored daily with a scoring system, as described previously, 31 with minor modifications. The scoring system was as follows: (a) normal stool (score = 0); (b) color change/consistency (score = 1); (c) presence of wet tail or mucosa (score = 2); and (d) liquid stools (score = 3).…”