FIGURE 3-2 Model of the interaction between dynamics of the gut microbiota and C. difficile in antibiotic-treated mice, with clinical outcome being determined by the balance between recovery of the indigenous gut microbiota following antibiotic withdrawal and growth of the C. difficile population.
SOURCE: Reeves et al., 2011.

Young’s team repeated the experiment using cefoperazone instead of clindamycin and observed that all mice administered cefoperazone died as soon as they were infected with C. difficile. Moreover, colonization resistance was lowered so much that their microbiomes became pure cultures of C. difficile, and the microbiota were unable to restore colonization resistance even after some recovery time.

Young’s interpretation of the results is that colonization resistance recovery following an antibiotic assault seems to depend on which is happening faster—growth of the indigenous microbiota or growth of C. difficile (see Figure 3-2). Restoring balance in the community, or preventing imbalance, could be the basis for yet another new therapeutic approach to managing C. difficile. For example, Young mentioned the dissertation research of one of his students demonstrating that Lachnospiraceae bacteria are associated with greater colonization resistance. He wondered whether restoring balance might be simply a matter of adding “more bugs” in the “right combination.”

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