Antibiotic-Induced Dysbiosis Predicts Mortality in an Animal Model of Clostridium difficile Infection

Abstract

Antibiotic disruption of the intestinal microbiota favors colonization by 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. We administered either moxifloxacin ( = 70) or clindamycin ( = 60) to hamsters by subcutaneous injection from day 1 (D) to D and challenged them with a toxigenic strain at D Hamsters received various doses of a charcoal-based adsorbent, DAV131A, to modulate intestinal antibiotic concentrations. Gut dysbiosis was evaluated at D and D using diversity indices determined from 16S rRNA gene profiling. Survival was monitored until D We analyzed the relationship between fecal antibiotic concentrations and dysbiosis at the time of challenge and studied their capacity to predict subsequent death of the animals. Increasing 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 ( < 10 for the change of Shannon index in moxifloxacin-treated animals and < 10 in clindamycin-treated animals). The Shannon diversity index and unweighted UniFrac distance best predicted death, with areas under the receiver operating curve (ROC) of 0.89 (95% confidence interval [CI], 0.82, 0.95) and 0.95 (0.90, 0.98), respectively. Altogether, moxifloxacin and clindamycin disrupted the diversity of the intestinal microbiota with a dependency on the DAV131A dose; mortality after challenge was related to the intensity of dysbiosis in similar manners with the two antibiotics.

Modeling the bacterial dynamics in the gut microbiota following an antibiotic‐induced perturbation

“…Generally, such a shift is associated with modifications in the bacterial composition of the ecosystem and a reduction in alpha biodiversity, which are likely to allow the establishment of a new balance within the bacterial ecosystem and the colonization of the ecosystem by resistant bacterial. 7 , 10 , 11 , 12 , 13 Accordingly, understanding the altered bacterial dynamics following antibiotics administration is critical to characterize their harmful consequences. The most natural mathematical framework for studying bacterial dynamics is the generalized Lotka‐Volterra model, which can account for both interactions and the effect of exogeneous factors.…”

“…For decades, they have been recognized to profoundly disturb the ecological equilibrium of the gut microbiota, a phenomenon called dysbiosis. Generally, such a shift is associated with modifications in the bacterial composition of the ecosystem and a reduction in alpha biodiversity, which are likely to allow the establishment of a new balance within the bacterial ecosystem and the colonization of the ecosystem by resistant bacterial 7,10–13 . Accordingly, understanding the altered bacterial dynamics following antibiotics administration is critical to characterize their harmful consequences.…”

<i>Clostridioides difficile</i> antibody response of colorectal cancer patients versus clinically healthy individuals

“…C. difficile has been proven to proliferate during antibiotic-induced dysbiosis in the gut microenvironment [ 28 , 29 , 30 , 31 ]. Antibiotic treatments deplete the commensal bacteria in the gut, which are known to metabolize primary bile acids into secondary bile acids that, in turn, inhibit the proliferation of C. difficile .…”

Dual photothermal nanocomposites for drug-resistant infectious wound management

“…9,10 Antibiotic-based therapy, which interferes with the normal metabolic processes of pathogenic bacteria, has several inherent disadvantages, including significant systemic cytotoxicity, poor solubility, and dose dependence. [11][12][13] The wide use of antibiotics has been associated with the emergence of multi-drug resistant (MDR) bacterial strains, 14 such as methicillin-resistant Staphylococcus aureus (MRSA) and vancomycinresistant Staphylococcus aureus (VRSA). 15 Bacterial resistance has been an escalating global threat to humans over the past few decades.…”