| 抄録 |
Nonsteroidal anti-inflammatory drugs（NSAID）induce ulcerations in the small intestine in a few patients. Although there were reports showing that bacteria play a major role in the formation of intestinal ulcers induced by NSAID, there was little information on culture studies, gnotbiotic rats and bacterial protection against ulcer formation. In this review, I introduce Japanese studies by Prof. Ohnishi and colleague to elucidate the cause of the small intestine ulcers by NSAID for the first time in the world. They administered one of the NSAID, 5-bromo-2-（4-fluorophenyl）-3-（4-methylsulfonylphenyl）thiophene（BFMeT）to Wistar rats. 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. In the group of rats with ulcers induced by BFMeT, the Gram-positive rods decreased and the Gram-negative rods including Escherichia coli, Klebsiella, Proteus and Bacteroides increased. 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. They reveal that enteric gram-negative 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.（Uejima M, et al, Microbiol Immunol. 1996；40：553-60, Kinouchi T, et al. Microbiol Immunol. 1998；42：347-55, Bing SR, et al. Microbiol Immunol. 1998；42：745-53, Hagiwara M, et al. J Med Invest. 2004；51：43-51.） |
