Clostridium difficile, a prevalent hospital-acquired pathogen, colonizes the gut after perturbation of the intestinal microbiota. Current antibiotic treatment options result in high recurrence rates, highlighting the need to identify alternative approaches to control this disease. Recent studies demonstrate that fecal microbiota transplantation (FMT) is an increasingly accepted and highly effective alternative treatment for cases of recurrent C. difficile infection, yet the exact mechanism of FMT-mediated clearance is undefined. We hypothesize that the commensal bacteria derived from the FMT interact with the host’s immune system to drive the clearance of C. difficile infection. This study assessed the role of the cytokine interleukin 17a (IL-17a), which is upregulated following C. difficile infection, in FMT-mediated clearance of C. difficile. In the acute phase of infection both antibiotic pre-treated Il17a-/- mice and littermate-control Il17a+/- mice recovered comparably and established a chronic infection of the large intestine. Chronically infected Il17a-/- and Il17a+/- mice treated with PBS maintained a high C. difficile burden whereas Il17a-/- and Il17a+/- mice treated with the FMT exhibited a 1-2 log-fold decrease in C. difficile colonization as early as four days after treatment. By day 22 post-treatment, FMT treated mice had significantly reduced C. difficile burden and toxin compared to PBS treated control mice and there was no difference in C. difficile clearance between FMT treated Il17a-/- and Il17a+/- groups. These results demonstrate that FMT-mediated clearance of C. difficile is independent of IL-17a expression. Further elucidation of the interplay between FMT and the recipient’s immune system will likely identify novel biochemical pathways that support successful FMT and improve treatment strategies.

Role of IL-17a in fecal microbiota transplant mediated clearance of C. Difficile infection

253rd National Meeting (2017)

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