title: Introduction: understanding mechanisms of the actions of rifaximin in selected gastrointestinal diseases.
abstract: BACKGROUND
  Historically, the beneficial effects of the nonsystemic oral agent rifaximin on various gastrointestinal (GI) disorders have been attributed to direct antibiotic activity on gut microbiota. However, data are accumulating to suggest that other nonantibacterial effects may be involved in rifaximin efficacy.
  
  
  OBJECTIVE
  To explore the mechanisms of action of rifaximin that may underlie its clinical benefits in travellers' diarrhoea, hepatic encephalopathy and other cirrhosis complications, inflammatory bowel diseases, and irritable bowel syndrome with diarrhoea.
  
  
  METHODS
  Gastroenterology experts convened a round-table discussion to address clinical and pre-clinical rifaximin data pertaining to select GI diseases and the potential mechanisms of action that underlie rifaximin efficacy profiles. As preparation, the literature was searched for publications related to rifaximin, its mechanisms of action, and its efficacy in travellers' diarrhoea, hepatic encephalopathy and other cirrhosis-related complications, inflammatory bowel diseases and irritable bowel syndrome.
  
  
  RESULTS
  Gut microbiota dysbiosis and proinflammatory activities are thought to significantly contribute to disease pathophysiology of these conditions. Rifaximin may resolve gut microbiota dysbiosis by promoting GI colonisation of beneficial bacterial species without drastic alterations in overall diversity. Rifaximin-induced changes in the production and metabolism of bacteria-produced agents (e.g. deoxycholic acid, lipopolysaccharides) also may help preserve normal gut microbiota. Rifaximin may suppress local and systemic inflammatory processes by preserving epithelial function (e.g. limiting bacterial translocation), modulating bacterial virulence and reducing proinflammatory cytokine production.
  
  
  CONCLUSIONS
  The commonality of pathological mechanisms underlying multiple GI diseases and the ability of rifaximin to modulate the gut microenvironment (i.e. gut microenvironment modulator) may explain its diverse efficacy profile.
authors.affiliation: Center for Infectious Diseases, The University of Texas School of Public Health, Baylor College of Medicine, Kelsey Research Foundation, Houston, TX, USA.
authors.forename: H L
authors.initials: HL
authors.lastname: DuPont
mesh_terms: D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D003967:Diarrhea / Q000188:drug therapy; D005765:Gastrointestinal Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D005767:Gastrointestinal Diseases / Q000188:drug therapy* / Q000503:physiopathology; D000069196:Gastrointestinal Microbiome; D006501:Hepatic Encephalopathy / Q000188:drug therapy; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy; D043183:Irritable Bowel Syndrome / Q000188:drug therapy; D012294:Rifamycins / Q000494:pharmacology* / Q000627:therapeutic use*; D000078262:Rifaximin
chemical_list: D000900:Anti-Bacterial Agents; D005765:Gastrointestinal Agents; D012294:Rifamycins; D000078262:Rifaximin