Development of animal model for enterohemorrhagic Escherichia coli infection

产生志贺毒素的大肠杆菌(STEC)感染是人类严重腹泻疾病的罪魁祸首，这些细菌最近已成为儿童和老年人肾功能衰竭和脑炎的主要原因。为了建立STEC感染的快速诊断方法或方法/药物，建立动物模型是必要的。常规小鼠或大鼠对STEC不敏感。使用诺生菌小鼠、抗生素治疗小鼠或营养不良小鼠。从正常小鼠身上切除盲肠会对胃肠道的微生物生态造成重大干扰。定植阻力的永久性降低导致兼性厌氧大肠菌群浓度增加了1000倍。与大肠菌群数量增加相一致的是，主导啮齿动物肠道的严格厌氧梭形细菌的数量减少，导致挥发性脂肪酸水平降低。由于挥发性脂肪酸是寄生在啮齿动物肠道的厌氧菌的主要代谢终产物，主要在盲肠产生，因此脂肪酸水平的下降很可能是由于肠道正常微生物区系的变化。盲肠切除有可能成为研究不能在正常小鼠肠道内定植的肠道病原体的有效模型。我们成功地建立了这一模型，尽管STEC被攻击到盲肠切除的小鼠中不能在被攻击的小鼠中定植和引起腹泻。

Infections due to Shiga toxin-producing Escherichia coli (STEC) are responsible for severe diarrheal diseases in humans, and these bacteria have recently emerged as a leading cause of renal failure and encephalitis in children and the aged. To develop rapid diagnosis methods or methods/medicines to treat patients infected with STEC, animal model are necessary. Conventional mice or rat are not sensitive for STEC. Gnotobiotic mice, antibiotics treated mice or malnutritional mice are used. Removal of the cecum from normal mice caused a major perturbation of the microbial ecology of the gastrointestinal tract. There was a permanent reduction in colonization resistance resulting in a 1,000-fold increase in the concentration of facultatively anaerobic coliform bacteria. Coincident with this increase in coliform counts was a decrease in the numbers of strictly anaerobic fusiform bacteria that dominate the rodent intestinal tract, resulting in reduced levels of volatile fatty acids. As the volatile fatty acids are major metabolic end products of anaerobic bacteria that colonize the rodent intestine and are produced mainly in the cecum, it was likely that the decrease in fatty acid levels was due to changes in the normal microbiota of the intestine. Cecectomized are likely to be a useful model for study of Intestinal pathogen that can not colonize in the intestine of normal mice. We succeeded to development of this model, though STEC challenged into cecectomized mice could not colonize and cause diarrea in challenged mice.