title: Rifaximin alters intestinal bacteria and prevents stress-induced gut inflammation and visceral hyperalgesia in rats.
abstract: OBJECTIVE
  Rifaximin is used to treat patients with functional gastrointestinal disorders, but little is known about its therapeutic mechanism. We propose that rifaximin modulates the ileal bacterial community, reduces subclinical inflammation of the intestinal mucosa, and improves gut barrier function to reduce visceral hypersensitivity.
  
  
  METHODS
  We induced visceral hyperalgesia in rats, via chronic water avoidance or repeat restraint stressors, and investigated whether rifaximin altered the gut microbiota, prevented intestinal inflammation, and improved gut barrier function. Quantitative polymerase chain reaction (PCR) and 454 pyrosequencing were used to analyze bacterial 16S ribosomal RNA in ileal contents from the rats. Reverse transcription, immunoblot, and histologic analyses were used to evaluate levels of cytokines, the tight junction protein occludin, and mucosal inflammation, respectively. Intestinal permeability and rectal sensitivity were measured.
  
  
  RESULTS
  Water avoidance and repeat restraint stress each led to visceral hyperalgesia, accompanied by mucosal inflammation and impaired mucosal barrier function. Oral rifaximin altered the composition of bacterial communities in the ileum (Lactobacillus species became the most abundant) and prevented mucosal inflammation, impairment to intestinal barrier function, and visceral hyperalgesia in response to chronic stress. Neomycin also changed the composition of the ileal bacterial community (Proteobacteria became the most abundant species). Neomycin did not prevent intestinal inflammation or induction of visceral hyperalgesia induced by water avoidance stress.
  
  
  CONCLUSIONS
  Rifaximin alters the bacterial population in the ileum of rats, leading to a relative abundance of Lactobacillus. These changes prevent intestinal abnormalities and visceral hyperalgesia in response to chronic psychological stress.
authors.affiliation: Gastroenterology Research Unit, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan.
authors.forename: Dabo
authors.initials: D
authors.lastname: Xu
authors.affiliation: Gastroenterology Research Unit, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan.
authors.forename: Jun
authors.initials: J
authors.lastname: Gao
authors.affiliation: Gastroenterology Research Unit, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan.
authors.forename: Merritt
authors.initials: M
authors.lastname: Gillilland
authors.affiliation: Gastroenterology Research Unit, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan.
authors.forename: Xiaoyin
authors.initials: X
authors.lastname: Wu
authors.affiliation: Gastroenterology Research Unit, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan.
authors.forename: Il
authors.initials: I
authors.lastname: Song
authors.affiliation: Gastroenterology Research Unit, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan.
authors.forename: John Y
authors.initials: JY
authors.lastname: Kao
authors.affiliation: Gastroenterology Research Unit, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan. Electronic address: cowyang@med.umich.edu.
authors.forename: Chung
authors.initials: C
authors.lastname: Owyang
mesh_terms: D000284:Administration, Oral; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D016207:Cytokines / Q000378:metabolism; D004269:DNA, Bacterial / Q000032:analysis; D004334:Drug Administration Schedule; D005765:Gastrointestinal Agents / Q000494:pharmacology* / Q000627:therapeutic use; D006930:Hyperalgesia / Q000209:etiology / Q000378:metabolism / Q000382:microbiology / Q000517:prevention & control*; D007079:Ileitis / Q000209:etiology / Q000378:metabolism / Q000382:microbiology / Q000517:prevention & control*; D007082:Ileum / Q000187:drug effects* / Q000378:metabolism / Q000382:microbiology; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000382:microbiology; D008297:Male; D064307:Microbiota / Q000187:drug effects* / Q000235:genetics; D009355:Neomycin / Q000494:pharmacology / Q000627:therapeutic use; D062793:Occludin / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012149:Restraint, Physical; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012294:Rifamycins / Q000494:pharmacology* / Q000627:therapeutic use; D000078262:Rifaximin; D017422:Sequence Analysis, DNA; D013315:Stress, Psychological
chemical_list: D015415:Biomarkers; D016207:Cytokines; D004269:DNA, Bacterial; D005765:Gastrointestinal Agents; D062793:Occludin; C568987:Ocln protein, rat; D012294:Rifamycins; D009355:Neomycin; D000078262:Rifaximin
keywords: Antibiotic; CRD; EMG; Gut Flora; IBS; IFN-gamma; IL; Intestine; Irritable Bowel Syndrome; PCR; PXR; RF; TNF-α; VMR; WAS; colorectal distention; electromyographic; interferon-gamma; interleukin; irritable bowel syndrome; polymerase chain reaction; pregnane X receptor; rRNA; ribosomal RNA; rifaximin; tumor necrosis factor−α; visceromotor response; water avoidance stress