ROLE OF INTESTINAL BACTERIA IN ILEAL ULCER FORMATION IN RATS TREATED WITH A NONSTEROIDAL ANTIINFLAMMATORY DRUG

The role of intestinal bacteria in induction and repression of ulcer f ormation in the ileum of rats treated with one of the nonsteroidal ant iinflammatory drugs (NSAIDs), romo-2-(4-fluorophenyl)-3-(4-methylsulfo nylphenyl) thiophene (BFMeT), was examined in this study. BFMeT was ad ministered by intragastric gavage once at doses of 500-1,500 mg/kg of body weight to Wistar rats treated with and without antibiotics (bacit racin, neomycin, streptomycin), germ-free rats and gnotobiotic rats, a nd 72 hr later their gastrointestinal tracts were examined for ulcer f ormation. A single oral administration of BFMeT induced ileal ulcers i n 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 adolesc entis or Lactobacillus acidophilus also had no intestinal ulcers, Howe ver, 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 Bifidobacteriu m breve and Streptococcus thermophilus, when given as drinking water, inhibited ulcer formation in the ileum of rats treated with BFMeT, Gra m 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 incre ased by 37.3%. However, in the group of rats administered the Bifidoba cterium 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 facult atively anaerobic rods E. coli, Klebsiella and Proteus were increased in the ulcerated ileum of rats treated with BFMeT, suggesting that the se bacteria are associated with ulcer formation in rats treated with N SAIDs, and that Lactobacillus and Bifidobacterium inhibit it by repres sing the growth of ulcer-inducing bacteria.