Proton-Pump Inhibitor Exposure Aggravates Clostridium difficile-Associated Colitis: Evidence from a Mouse Model

Yuan Pin Hung, Wen Chien Ko, Po Han Chou, Yi Hsuan Chen, Hsiao Ju Lin, Ya Hui Liu, Hung Wen Tsai, Jen Chieh Lee, Pei Jane Tsai

Research output: Contribution to journalArticlepeer-review

21 Citations (Scopus)

Abstract

Background. Clostridium difficile is currently the leading cause of infectious diarrhea in hospitalized patients. In addition to the infection due to toxigenic C. difficile in the gastrointestinal tract of susceptible hosts, other predisposing factors for C. difficile infection (CDI) are identified, including advanced age, a prolonged hospital stay, and use of acid-suppressive drugs. Of note, exposure to gastric acid-reducing agents, such as H2 blockers and proton pump inhibitors (PPIs), remains a controversial risk factor, and has been associated with CDI in some studies but not in others. A mouse model of antibiotic-associated clostridial colitis was established to examine the role of PPIs for CDI. Materials and Methods. A mouse model of antibiotic-associated clostridial colitis was set up. NF-κB reporter mice were used to address the in vivo spatial and temporal inflammatory patterns of C. difficile-associated colitis. Serum levels of lipopolysaccharide and dextran-FITC were measured to reflect the barrier permeability of affected intestines. Results. Mice with CDI that were exposed to PPI exhibited greater losses of stool consistency and body and cecal weights than those that were not exposed to PPI. Further, more neutrophilic infiltrations, epithelial damage, and inflammatory cytokine expression were noted in colon specimens of the mice with PPI exposure. More-evident inflammatory responses were detected by in vivo imaging of NF-κB reporter mice with CDI that were exposed to PPI. Gut barrier permeability was increased to a greater extent, as reflected by higher serum levels of lipopolysaccharide and dextran-FITC in mice with CDI that were exposed to PPI. Conclusions. Our mouse model demonstrates that PPI exposure increases the severity of intestinal inflammation in mice with C. difficile-associated colitis.

Original languageEnglish
Pages (from-to)654-663
Number of pages10
JournalJournal of Infectious Diseases
Volume212
Issue number4
DOIs
Publication statusPublished - 2015 Aug 15

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Infectious Diseases

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