Role of intestinal bacteria in small intestinal ulcer formation and prevention in rats treated with a nonsteroidal antiinflammatory drug.

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This study examined the role of intestinal bacteria in induction and repression of ulcer formation in the ileum of rats treated with one of the nonsteroidal antiinflammatry drugs (NSAIDs), 5-bromo-2-(4-fluorophenyl)-3-(4-methylsulfonylphenyl) thiophene (BFMeT). BFMeT was administered by intragastric gavage once at doses of 500-1500 mg/kg of body weight in a volume of 10 ml/kg to Wistar rats treated with and without antibiotics (bacitracin, neomycin, streptomycin), germ-free rats and gnotobiotic rats, and 72 hours later their gastrointestinal tracts were examined for ulcer formation. 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 wi … More th Eubacterium limosum or Escherichia coli. The number of viable microorganisms in the ulcerated ileum was 13.6-fold higher in the aerobic culture and 8.8-fold higher in the anaerobic culture when compared with that in the normal rats. An overnight culture of B.adolescentis or L.acidophilus or yogurt containing Bifidobacterium breve and Streptococcus thermophilus, when given as drinking water, inhibited the 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, 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 Escherichia coli, Klebsiella and Proteus were increased in the ulcerated ileum of rats treated with BFMeT,suggesting that these bacteria are associated with the ulcer formation in rats treated with NSAIDs, and that Lactobacillus and Bifidobacterium inhibit it by repressing the growth of ulcer-inducing bacteria. Less