Misoprostol protects mice against severe Clostridium difficile infection and promotes recovery of the gut microbiota after antibiotic perturbation

Abstract Clostridium difficile infection (CDI) is one of the most common nosocomial infections worldwide and an urgent public health threat. Epidemiological and experimental studies have demonstrated an association between nonsteroidal anti-inflammatory drug (NSAID) exposure and enhanced susceptibility to, and severity of, CDI. NSAIDs target cyclooxygenase enzymes and inhibit the production of prostaglandins (PGs), but the therapeutic potential of exogenous introduction of PGs for the treatment of CDI has not been explored. In this study, we report that treatment with the FDA-approved stable PGE 1 analogue, misoprostol, protects mice against C. difficile -associated mortality, intestinal pathology, and CDI-mediated intestinal permeability. Furthermore, we report that the effect of misoprostol on the gastrointestinal tract contributes to increased recovery of the gut microbiota following antibiotic perturbation. Together, these data implicate PGs as an important host-factor associated with recovery to C. difficile -associated disease and demonstrate the potential for misoprostol in the treatment of CDI. Further studies to explore the safety and efficacy of misoprostol treatment of CDI in humans is needed.