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Anaerobe. 2019 Aug;58:89-94. doi: 10.1016/j.anaerobe.2019.06.006. Epub 2019 Jun 17.

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

Author information

1
Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, United States; Division of Protective Immunity, Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA, United States; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States.
2
Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, United States.
3
Department of Pathology, University of Massachusetts Medical School, Worcester, MA, USA.
4
Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, United States.
5
Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, United States; Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, United States. Electronic address: d.aronoff@vumc.org.

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 PGE1 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.

KEYWORDS:

Clinical pharmacology; Colitis; Microbiome; NSAIDs; Prostaglandins

PMID:
31220605
PMCID:
PMC6697607
[Available on 2020-08-01]
DOI:
10.1016/j.anaerobe.2019.06.006

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