Role of Intestinal Bacteria in Ileal Ulcer Formation in Rats Treated with a Nonsteroidal Antiinflammatory Drug
Abstract
The role of intestinal bacteria in induction and repression of ulcer formation in the ileum of rats treated with one of the nonsteroidal antiinflammatory drugs (NSAIDs), 5‐bromo‐2‐(4‐fluorophenyl)‐3‐(4‐methylsulfonylphenyl) thiophene (BFMeT), was examined in this study. BFMeT was administered by intragastric gavage once at doses of 500‐1,500 mg/kg of body weight to Wistar rats treated with and without antibiotics (bacitracin, neomycin, streptomycin), germ‐free rats and gnotobiotic rats, and 72 hr later their gastrointestinal tracts were examined for ulcer formation. A single oral administration of BFMeT induced ileal ulcers in specific pathogen‐free rats. However, the rats given antibiotics to reduce the intestinal bacteria had no ulcers. BFMeT‐treated germ‐free rats and gnotobiotic rats mono‐associated with Bifidobacterium adolescentis or Lactobacillus acidophilus also had no intestinal ulcers. However, the drug induced ileal ulcers in gnotobiotic rats mono‐associated with Eubacterium limosum or Escherichia coli. An overnight culture of B. adolescentis or L. acidophilus or yogurt containing Bifidobacterium breve and Streptococcus thermophilus, when given as drinking water, inhibited ulcer formation in the ileum of rats treated with BFMeT. Gram staining of the ileal contents of normal rats revealed that 97.4% of the stained microorganisms were Gram‐positive rods and only 1.2% were Gram‐negative rods. In the group of rats with ulcers induced by BFMeT, the Gram‐positive rods decreased by 56.4% and the Gram‐negative rods including Escherichia coli, Klebsiella, Proteus and Bacteroides increased by 37.3%. However, in the group of rats administered the Bifidobacterium culture, the Lactobacillus culture or yogurt, the percentages of the Gram‐negative rods were decreased. Although Lactobacillus was a major bacterium in the ileum of normal rats, the Gram‐negative facultatively anaerobic rods E. coli, Klebsiella and Proteus were increased in the ulcerated ileum of rats treated with BFMeT, suggesting that these bacteria are associated with ulcer formation in rats treated with NSAIDs, and that Lactobacillus and Bifidobacterium inhibit it by repressing the growth of ulcer‐inducing bacteria.
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Germ-free mice are less susceptible to intestinal lesions induced by NSAIDs and NSAID-induced enteropathy is transferable via microbiota.
“Moreover, germ-free mice are less susceptible to intestinal lesions induced by NSAIDs and it has been documented that NSAID-induced enteropathy is transferable via microbiota[98,101,102].”
From Proton pump inhibitors and dysbiosis: current knowledge and aspects to be clarified (2019) · cites this paper as [101]
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- Authors
- Uejima, M., Kinouchi, T., Kataoka, K., Hiraoka, I., & Ohnishi, Y.
- Affiliations
- Otsuka (Japan) (JP)
- Tokushima University (JP)
- Corresponding author
- Ohnishi, Yoshinari
- ORCID
- Kataoka, Keiko
- Venue
- Microbiology and Immunology
- Publisher
- Wiley
- Published
- 1996-08
- Volume
- 40
- Issue
- 8
- Pages
- 553-560
- ISSN
- 0385-5600 (ISSN-L)
- 1348-0421
- OpenAlex
- W2092434579
- Cited by
- 110
- References
- 34
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 5 · 2023: 4 · 2022: 5 · 2021: 8 · 2020: 7 · 2019: 9 · 2018: 6 · 2017: 9 · 2016: 4 · 2015: 6 · 2014: 11 · 2013: 4 · 2012: 8
- FWCI
- 0.25
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Microbiology and Immunology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Pharmacology › Inflammatory mediators and NSAID effects
- Life Sciences › Agricultural and Biological Sciences › Food Science › Probiotics and Fermented Foods
- Keywords
- intestinal bacteria, nonsteroidal anti-inflammatory drugs, germ-free rats, gnotobiotic rats, Bifidobacterium adolescentis, Lactobacillus acidophilus, yogurt, Escherichia coli, Klebsiella, Proteus, Bacteroides, Gram-negative bacteria, ulcer prevention
- MeSH terms
- Animals, Anti-Inflammatory Agents, Non-Steroidal, Anti-Bacterial Agents, Bacteria, Germ-Free Life, Ileal Diseases, Intestines, Specific Pathogen-Free Organisms, Thiophenes, Ulcer, Rats, Wistar, Rats
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