Abstract
Clostridium difficile infections (CDI) are a major cause of antibiotic-associated diarrhea. It is hypothesized that CDI develops due to the antibiotic-induced disruption of the intestinal microbial community structure, which allows C. difficile to flourish. Here, we pre-treated weaned pigs with the antibiotics Clindamycin or Ciprofloxacin for 1 day, and subsequently inoculated them with a human and pig enteropathogenic C. difficile strain 078 spores. Body temperature, clinical signs of disease, and the fecal microbiome were monitored daily for 15 days. Clindamycin had a stronger effect on the pigs than Ciprofloxacin, resulting in drastic shifts in the fecal microbiome, decreases in microbial diversity and significant increases in body temperature, even in the absence of C. difficile. Fecal shedding of C. difficile was detectable for 3 and 9 days in Ciprofloxacin and Clindamycin treated pigs inoculated with C. difficile, respectively, and in both cases decreased cell proliferation rates were detected in colon tissue. The timing of C. difficile shedding coincided with the decrease in a large cluster of Firmicutes following Clindamycin treatment, a pattern which was also independent of C. difficile inoculation. The observed community patterns suggest that successional dynamics following antibiotic treatment facilitate C. difficile establishment. The similarities between the microbiome responses observed in our study and those previously reported in CDI-infected humans further support the utility of adult pigs as models for the study of CDI.
Highlights
Clostridium difficile infections (CDI) are a major cause of hospital-associated and antibiotic-associated diarrhea in humans (Monaghan, 2015)
The mean temperature for pigs from both the Ciprofloxacin treatment (Cip) C. dif and Clindamycin treatment (Clin) C. dif treatments was highest on day 1 (39.71and 39.69◦C, respectively), but neither was significantly different from temperatures exhibited before the C. difficile challenge
Multiple studies have shown that an altered intestinal microbial community structure may allow the germination and colonization of indigenous or externally-derived C. difficile, which results in CDI, the specific mechanisms behind this phenomenon are unknown (Britton and Young, 2014)
Summary
Clostridium difficile infections (CDI) are a major cause of hospital-associated and antibiotic-associated diarrhea in humans (Monaghan, 2015). It is hypothesized that the residing gut microbiota is important in the maintenance of C. difficile colonization resistance in healthy individuals, and that CDI is associated with dysbiosis of the intestinal microbiota caused by antibiotic use (Reeves et al, 2011). Antibiotics disrupt the intestinal microbial community structure, decreasing its colonization resistance and Clostridium difficile Infection in Adult Pig Models promoting the germination and colonization of C. difficile spores in the colon (Paterson, 2004). The shift in microbial community structure that induces sensitivity to C. difficile infections has not been studied at a high temporal resolution due to lack of longitudinal studies which sample the intestinal microbiome prior to antibiotic administration and C. difficile infection
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