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Rifaximin alters intestinal bacteria and prevents stress-induced gut inflammation and visceral hyperalgesia in rats.
Gastroenterology. 2014 Feb; 146(2):484-96.e4.G

Abstract

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.

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Authors+Show Affiliations

Xu D
Gastroenterology Research Unit, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan.
Gao J
Gastroenterology Research Unit, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan.
Gillilland M
Gastroenterology Research Unit, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan.
Wu X
Gastroenterology Research Unit, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan.
Song I
Gastroenterology Research Unit, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan.
Kao JY
Gastroenterology Research Unit, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan.
Owyang C
Gastroenterology Research Unit, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan. Electronic address: cowyang@med.umich.edu.

MeSH

Administration, OralAnimalsBiomarkersBlotting, WesternCytokinesDNA, BacterialDrug Administration ScheduleGastrointestinal AgentsHyperalgesiaIleitisIleumImmunohistochemistryIntestinal MucosaMaleMicrobiotaNeomycinOccludinRatsRats, WistarRestraint, PhysicalReverse Transcriptase Polymerase Chain ReactionRifamycinsRifaximinSequence Analysis, DNAStress, Psychological

Pub Type(s)

Evaluation Study
Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

24161699

Clinical Trial Links

Rifaximin Predicts the Complications of Decompensated Cirrhosis
Rifaximin Reduces the Complications of Decompensated Cirrhosis: a Randomized Controlled Trial

Citation

Xu, Dabo, et al. "Rifaximin Alters Intestinal Bacteria and Prevents Stress-induced Gut Inflammation and Visceral Hyperalgesia in Rats." Gastroenterology, vol. 146, no. 2, 2014, pp. 484-96.e4.
Xu D, Gao J, Gillilland M, et al. Rifaximin alters intestinal bacteria and prevents stress-induced gut inflammation and visceral hyperalgesia in rats. Gastroenterology. 2014;146(2):484-96.e4.
Xu, D., Gao, J., Gillilland, M., Wu, X., Song, I., Kao, J. Y., & Owyang, C. (2014). Rifaximin alters intestinal bacteria and prevents stress-induced gut inflammation and visceral hyperalgesia in rats. Gastroenterology, 146(2), 484-e4. https://doi.org/10.1053/j.gastro.2013.10.026
Xu D, et al. Rifaximin Alters Intestinal Bacteria and Prevents Stress-induced Gut Inflammation and Visceral Hyperalgesia in Rats. Gastroenterology. 2014;146(2):484-96.e4. PubMed PMID: 24161699.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Rifaximin alters intestinal bacteria and prevents stress-induced gut inflammation and visceral hyperalgesia in rats. AU - Xu,Dabo, AU - Gao,Jun, AU - Gillilland,Merritt,3rd AU - Wu,Xiaoyin, AU - Song,Il, AU - Kao,John Y, AU - Owyang,Chung, Y1 - 2013/10/22/ PY - 2013/04/05/received PY - 2013/10/14/revised PY - 2013/10/16/accepted PY - 2013/10/29/entrez PY - 2013/10/29/pubmed PY - 2014/3/19/medline KW - Antibiotic KW - CRD KW - EMG KW - Gut Flora KW - IBS KW - IFN-gamma KW - IL KW - Intestine KW - Irritable Bowel Syndrome KW - PCR KW - PXR KW - RF KW - TNF-α KW - VMR KW - WAS KW - colorectal distention KW - electromyographic KW - interferon-gamma KW - interleukin KW - irritable bowel syndrome KW - polymerase chain reaction KW - pregnane X receptor KW - rRNA KW - ribosomal RNA KW - rifaximin KW - tumor necrosis factor−α KW - visceromotor response KW - water avoidance stress SP - 484 EP - 96.e4 JF - Gastroenterology JO - Gastroenterology VL - 146 IS - 2 N2 - 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. SN - 1528-0012 UR - https://www.unboundmedicine.com/medline/citation/24161699/Rifaximin_alters_intestinal_bacteria_and_prevents_stress_induced_gut_inflammation_and_visceral_hyperalgesia_in_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0016-5085(13)01500-X DB - PRIME DP - Unbound Medicine ER -