Rifaximin Alters Intestinal Bacteria and Prevents Stress-Induced Gut Inflammation and Visceral Hyperalgesia in Rats

• Published in: Gastroenterology (New York, N.Y. 1943) Vol. 146; no. 2; pp. 484 - 496.e4
• Main Authors: Xu, Dabo, Gao, Jun, Gillilland, Merritt, Wu, Xiaoyin, Song, Il, Kao, John Y, Owyang, Chung
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.02.2014
• Subjects: Administration, Oral; Animals; Antibiotic; Biomarkers - metabolism; Blotting, Western; Cytokines - metabolism; DNA, Bacterial - analysis; Drug Administration Schedule; Gastroenterology and Hepatology; Gastrointestinal Agents - pharmacology; Gastrointestinal Agents - therapeutic use; Gut Flora; Hyperalgesia - etiology; Hyperalgesia - metabolism; Hyperalgesia - microbiology; Hyperalgesia - prevention & control; Ileitis - etiology; Ileitis - metabolism; Ileitis - microbiology; Ileitis - prevention & control; Ileum - drug effects; Ileum - metabolism; Ileum - microbiology; Immunohistochemistry; Intestinal Mucosa - drug effects; Intestinal Mucosa - metabolism; Intestinal Mucosa - microbiology; Intestine; Irritable Bowel Syndrome; Male; Microbiota - drug effects; Microbiota - genetics; Neomycin - pharmacology; Neomycin - therapeutic use; Occludin - metabolism; Rats; Rats, Wistar; Restraint, Physical; Reverse Transcriptase Polymerase Chain Reaction; Rifamycins - pharmacology; Rifamycins - therapeutic use; Rifaximin; Sequence Analysis, DNA; Stress, Psychological; colorectal distention; WAS; pregnane X receptor; PXR; water avoidance stress; ribosomal RNA; Intestine; Irritable Bowel Syndrome; visceromotor response; IBS; interleukin; interferon-gamma; EMG; polymerase chain reaction; Gut Flora; IL; rRNA; electromyographic; rifaximin; Antibiotic; CRD; IFN-gamma; RF; TNF-α; tumor necrosis factor−α; VMR; PCR
• ISSN: 0016-5085; 1528-0012
• DOI: 10.1053/j.gastro.2013.10.026

Background & Aims 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.