title: Proton pump inhibitors induce changes in colonocyte gene expression that may affect Clostridium difficile infection.
abstract: BACKGROUND
  Proton pump inhibitors seem to promote Clostridium difficile infection (CDI). Although the current literature suggests that this association is mediated through gastric acid suppression, there has been little investigation into whether a direct effect on expression of colonocyte genes may also have a role. The aim of this study was to investigate the effect of omeprazole on genome-wide gene expression in a human colonic cell line.
  
  
  METHODS
  T84 cell monolayers were treated with acid-activated omeprazole at 0, 1, 10, or 100 μmol/L for 48 hours. Cells were lysed and total RNA samples were reverse transcribed and used to generate biotinylated cRNA. Whole-genome transcript expression levels were then quantified using an Illumina HT-12 BeadChip microarray targeting 25,440 genes. Transcripts with a stringent minimum absolute fold change of 1.5 and an adjusted nominal P value <.05 (false discovery) were identified as being differentially expressed.
  
  
  RESULTS
  Significant changes in expression were observed for 322 colonocyte transcripts, including genes with potential implications for susceptibility to CDI. These genes include roles in cell junctions, toxin susceptibility, and bile acid metabolism and transport.
  
  
  CONCLUSIONS
  Omeprazole treatment decreases the expression of genes that have important functions in colonocyte integrity. Such impairment in colonocyte function may promote CDI.
authors.affiliation: Department of Surgery, The Pennsylvania State University, College of Medicine, Hershey, PA.
authors.forename: John P
authors.initials: JP
authors.lastname: Hegarty
authors.affiliation: Department of Surgery, The Pennsylvania State University, College of Medicine, Hershey, PA.
authors.forename: William
authors.initials: W
authors.lastname: Sangster
authors.affiliation: Department of Surgery, The Pennsylvania State University, College of Medicine, Hershey, PA.
authors.forename: Leonard R
authors.initials: LR
authors.lastname: Harris
authors.affiliation: Department of Surgery, The Pennsylvania State University, College of Medicine, Hershey, PA. Electronic address: ds692176@gmail.com.
authors.forename: David B
authors.initials: DB
authors.lastname: Stewart
mesh_terms: D002460:Cell Line; D016360:Clostridioides difficile; D003015:Clostridium Infections / Q000209:etiology*; D003106:Colon / Q000187:drug effects*; D015536:Down-Regulation / Q000187:drug effects*; D015870:Gene Expression / Q000187:drug effects*; D005819:Genetic Markers; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D009853:Omeprazole / Q000009:adverse effects*; D054328:Proton Pump Inhibitors / Q000009:adverse effects*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D005819:Genetic Markers; D054328:Proton Pump Inhibitors; D009853:Omeprazole