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

本研究探讨了肠道细菌在用非甾体抗炎药（NSAIDs）之一5-溴-2-（4-氟苯基）-3-（4-甲基磺酰基苯基）噻吩（BFMeT）治疗的大鼠回肠溃疡形成的诱导和抑制中的作用。将BFMeT以10 ml/kg的体积，500- 1500mg /kg的剂量灌胃给药给不含抗生素（杆菌肽、新霉素、链霉素）治疗的Wistar大鼠、无菌大鼠和非生物大鼠，72h后检查胃肠道溃疡形成情况。单次口服BFMeT诱导特定无病原体大鼠回肠溃疡。然而，给予抗生素以减少肠道细菌的大鼠没有溃疡。经bfmet处理的无菌大鼠和与青春期双歧杆菌或嗜酸乳杆菌单相关的无菌大鼠也没有肠道溃疡。然而，该药引起的无糖大鼠回肠溃疡多与灰泥真杆菌或大肠杆菌有关。与正常大鼠相比，好氧培养组溃疡回肠内活菌数量增加13.6倍，无氧培养组活菌数量增加8.8倍。将含有短双歧杆菌和嗜热链球菌的青少年芽杆菌或嗜酸乳杆菌或酸奶作为饮用水进行过夜培养，可抑制BFMeT治疗大鼠回肠溃疡的形成。正常大鼠回肠内容物革兰氏染色显示，97.4%的染色微生物为革兰氏阳性杆状体，仅1.2%为革兰氏阴性杆状体。在BFMet诱导的溃疡大鼠组中，革兰氏阳性杆状体减少56.4%，革兰氏阴性杆状体包括大肠杆菌、克雷伯氏菌、变形杆菌和拟杆菌增加37.3%。然而，在给予双歧杆菌培养物、乳酸杆菌培养物或酸奶的大鼠组中，革兰氏阴性棒的百分比有所下降。虽然乳杆菌是正常大鼠回肠中的主要细菌，但在BFMeT处理的大鼠溃疡回肠中，革兰氏阴性伴性厌氧棒大肠杆菌、克雷伯氏菌和变形杆菌数量增加，提示这些细菌与非甾体抗炎药处理的大鼠溃疡形成有关，乳杆菌和双歧杆菌通过抑制溃疡诱导菌的生长来抑制溃疡形成。少

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