Rifaximin Alters Intestinal Bacteria and Prevents Stress-Induced Gut Inflammation and Visceral Hyperalgesia in Rats
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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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Several studies linking the gut microbiota with visceral sensitivity have shown that increments in the Lactobacilli family are associated to visceral analgesic-like states.
“Moreover, several studies linking the gut microbiota with visceral sensitivity, have shown that increments in the Lactobacilli family (during probiotic treatment or during states of dysbiosis) are associated to visceral analgesic-like states.18,19,21,33”
From Antibiotic-induced dysbiosis alters host-bacterial interactions and leads to colonic sensory and motor changes in mice (2015) · cites this paper as [33]
Rifaximin treatment protected against intestinal inflammation, barrier damage, and visceral hypersensitivity caused by chronic water avoidance and repeat restraint stressors in Wistar rats.
“Moreover, rifaximin treatment protected against the intestinal inflammation, barrier damage, and visceral hypersensitivity caused by chronic water avoidance and repeat restraint stressors in Wistar rats (135).”
From Stress triggers flare of inflammatory bowel disease in children and adults (2019) · cites this paper as [135]
Lactobacillus species were significantly enriched after oral administration of rifaximin.
“A study found that Lactobacillus species were significantly enriched after oral administration of rifaximin.”
From Stress triggers flare of inflammatory bowel disease in children and adults (2019) · cites this paper as [135]
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- Authors
- Xu, D., Gao, J., Gillilland, M., Wu, X., Song, I., Kao, J. Y., & Owyang, C.
- Affiliations
- University of Michigan (US)
- Corresponding author
- Owyang, Chung
- Venue
- Gastroenterology
- Publisher
- Elsevier BV
- Published
- 2014-02
- Volume
- 146
- Issue
- 2
- Pages
- 484-496.e4
- ISSN
- 0016-5085 (ISSN-L)
- PMC
- PMC3939606
- OpenAlex
- W2125894152
- Cited by
- 271
- References
- 47
- Citations by year
- 2026: 12 · 2025: 17 · 2024: 15 · 2023: 26 · 2022: 21 · 2021: 30 · 2020: 11 · 2019: 22 · 2018: 27 · 2017: 30 · 2016: 24 · 2015: 21 · 2014: 15
- FWCI
- 18.86
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Gastroenterology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (P30DK34933, R01DK058913)
- Topics
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
- Keywords
- rifaximin, gut microbiota, visceral hypersensitivity, intestinal barrier function, Lactobacillus, neomycin, chronic psychological stress, water avoidance stress, occludin, intestinal permeability, rectal sensitivity, functional gastrointestinal disorders
- MeSH terms
- Rifaximin, Administration, Oral, Animals, DNA, Bacterial, Drug Administration Schedule, Gastrointestinal Agents, Hyperalgesia, Ileitis, Ileum, Immunohistochemistry, Intestinal Mucosa, Male, Neomycin, Restraint, Physical, Rifamycins, Stress, Psychological, Blotting, Western, Biomarkers, Cytokines, Rats, Wistar, Sequence Analysis, DNA, Reverse Transcriptase Polymerase Chain Reaction, Rats, Occludin, Microbiota
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