Antibiotic-induced dysbiosis predicts mortality in an animal model of Clostridium difficile infection

International audienceBackgroundAntibiotic disruption of the intestinal microbiota favors colonization by Clostridium difficile. Using a charcoal-based adsorbent to decrease intestinal antibiotic concentrations, we studied the relationship between antibiotic concentrations in feces and the intensity of dysbiosis, and quantified the link between this intensity and mortality.MethodsWe administered either moxifloxacin (n=70) or clindamycin (n=60) to hamsters by subcutaneous injection from day 1 (D1) to D5, and challenged them with a C. difficile toxigenic strain at D3. Hamsters received various doses of a charcoal-based adsorbent, DAV131A, to modulate intestinal antibiotic concentrations. Gut dysbiosis was evaluated at D0 and D3 using diversity indices determined from 16S rRNA gene profiling. Survival was monitored until D16. We analyzed the relationship between fecal antibiotic concentrations and dysbiosis at the time of C. difficile challenge and studied their capacity to predict subsequent death of the animals.ResultsIncreasing doses of DAV131A reduced fecal concentrations of both antibiotics, lowered dysbiosis and increased survival from 0% to 100%. Mortality was related to the level of dysbiosis (p<10-5 for the change of Shannon index in moxifloxacin-treated animals and p