title: Proton-Pump Inhibitor Exposure Aggravates Clostridium difficile-Associated Colitis: Evidence From a Mouse Model.
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.
  
  
  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.
authors: Department of Internal Medicine, Tainan Hospital, Ministry of Health and Welfare Department of Internal Medicine Graduate Institute of Clinical Medicine, National Health Research Institutes, Tainan, Taiwan.
authors: Yuan-Pin
authors: YP
authors: Hung
authors: Department of Internal Medicine Center for Infection Control, National Cheng Kung University Hospital Department of Medicine, National Cheng Kung University Medical College.
authors: Wen-Chien
authors: WC
authors: Ko
authors: Department of Medical Laboratory Science and Biotechnology.
authors: Po-Han
authors: PH
authors: Chou
authors: Department of Medical Laboratory Science and Biotechnology.
authors: Yi-Hsuan
authors: YH
authors: Chen
authors: Department of Internal Medicine, Tainan Hospital, Ministry of Health and Welfare Department of Internal Medicine Graduate Institute of Clinical Medicine, National Health Research Institutes, Tainan, Taiwan.
authors: Hsiao-Ju
authors: HJ
authors: Lin
authors: Department of Medical Laboratory Science and Biotechnology.
authors: Ya-Hui
authors: YH
authors: Liu
authors: Department of Pathology.
authors: Hung-Wen
authors: HW
authors: Tsai
authors: Department of Internal Medicine.
authors: Jen-Chieh
authors: JC
authors: Lee
authors: Department of Medical Laboratory Science and Biotechnology Center of Infectious Disease and Signaling Research, National Cheng Kung University.
authors: Pei-Jane
authors: PJ
authors: Tsai
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000009:adverse effects; D016360:Clostridioides difficile / Q000187:drug effects / Q000254:growth & development; D003106:Colon / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004761:Enterocolitis, Pseudomembranous / Q000139:chemically induced* / Q000473:pathology; D064098:Esomeprazole / Q000009:adverse effects*; D005243:Feces / Q000382:microbiology; D015964:Gene Expression Regulation, Bacterial; D017930:Genes, Reporter; D020397:Goblet Cells; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D054328:Proton Pump Inhibitors / Q000009:adverse effects*; D015854:Up-Regulation
chemical_list: D000900:Anti-Bacterial Agents; D016207:Cytokines; D016328:NF-kappa B; D054328:Proton Pump Inhibitors; D064098:Esomeprazole
keywords: C. difficile infection; NF-κB reporter mice; gut barrier permeability; mouse model; proton-pump inhibitor