Successional dynamics in the gut microbiome determine the success of Clostridium difficile infection in adult pig models.

Clostridium difficile infections (CDI) are a major cause of antibiotic-associated diarrhea. It ishypothesized that CDI develops due to the antibiotic-induced disruption of the intestinalmicrobial community structure, which allows C. difficile to flourish. Here, we pre-treatedweaned pigs with the antibiotics Clindamycin or Ciprofloxacin for one day, and subsequentlyinoculated them with a human and pig enteropathogenic C. difficile strain 078 spores. Bodytemperature, clinical signs of disease, and the fecal microbiome were monitored daily for 15days. Clindaycin had a stronger effect on the pigs than Ciprofloxacin, resulting in drastic shifts inthe fecal microbiome, decreases in microbial diversity and significant increases in bodytemperature, even in the absence of C. difficile. Fecal shedding of C. difficile was detectable for 3and 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 Firmicutesfollowing Clindamycin treatment, a pattern which was also independent of C. difficileinoculation. The observed community dynamics suggest that competitive interactions followingantibiotic treatment facilitate C. difficile establishment.