Abstract

Germ-free animals are an excellent tool for investigating bacterial interactions, because the effects of bacterial flora can be ruled out in such animals. We have examined the pathogenesis in various bacteria such as Clostridium difficile, enterohaemorrhagic Escherichia coli (EHEC) O157:H7 and Helicobacter pylori. Gnotobiotic mice (86%) mono-associated with C. difficile were dead within 2 days of infection, although all the SPF mice infected with C. difficile survived without any intestinal symptoms. Gnotobiotic mice mono-associated with EHEC developed ruffled fur and convulsion of limbs or hindleg weakness within 3 days afther the challenge, and all the mice were dead within 5 days of infection. Colonization of H. pylori with inflammatory changes in gastric mucosa was observed in gnotobiotic mice mono-associated with H. pylori. Probiotics are viable cell preparations that have been beneficial effects on the health of host. Clostridium butyricum is a butyric-acid producing gram-positive anaerobe, and C. butyricum M588 strain has been used as a probiotic for the treatment and prevention of diarrheal diseases. Using the above experimental animal models, we have examined the effects of the probiotic agent, Clostridium buttyricumM588 strain. Protective and prophylactic effect of the M588 strain on C. difficile, EHEC and H. pylori were demonstrated. In addition, detection of H. pylori in fecal samples by a immunomagnetic-bead separation technique was reported by using gnotobiotic mice mono-associated with H. pylori. We also examined the effect of bacterial flora on postimmunization gastritic following oral vaccination of mice with H. pylori heat shock protein 60 (HSP60) by using germ-free mice. It was concluded that the presence of bacterial flora appeared to contribute to the induction of postimmunization gastritis. The infection model for H. pylori using Mongolia gerbils is considered to be a useful, as gastric mucosal changes in stomach of Mongolian gerbils were similar to those in human stomachs following H. pylori infection. We have reported microbiological, histopathological and serological analyses after the long-term infection of Mongolian gerbils with H.pylori. In this model, marked atrophy of gastric mucosa, multiple cysts in the submucosa and squamous cell papilloma with hyperkeratosis were observed after long-term infection with H. pylori for 18 months. By using gerbil model, we also analyzed the significance of quorum sensing (QS) system in H. pylori. QS-defective, luxS mutant strain showed decreased motility and decreased colonization activity in the stomach of Mongolian gerbil, suggesting the involvement of QS in pathogenesis following H. pylori infection.

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