Rath H C, Schultz M, Freitag R, Dieleman L A, Li F, Linde H J, Schölmerich J, Sartor R B
Center for GI Biology and Disease, University of North Carolina, Chapel Hill, North Carolina, USA.
Infect Immun. 2001 Apr;69(4):2277-85. doi: 10.1128/IAI.69.4.2277-2285.2001.
Resident bacteria are incriminated in the pathogenesis of experimental colitis and inflammatory bowel diseases. We investigated the relative roles of various enteric bacteria populations in the induction and perpetuation of experimental colitis. HLA-B27 transgenic rats received antibiotics (ciprofloxacin, metronidazole, or vancomycin-imipenem) in drinking water or water alone in either prevention or treatment protocols. Mice were treated similarly with metronidazole or vancomycin-imipenem before or after receiving 5% dextran sodium sulfate (DSS). Germfree transgenic rats were colonized with specific-pathogen-free enteric bacteria grown overnight either in anaerobic or aerobic atmospheres. Nontransgenic rats colonized with anaerobic bacteria served as negative controls. Although preventive metronidazole significantly attenuated colitis in transgenic rats and DSS-treated mice, it had no therapeutic benefit once colitis was established. Ciprofloxacin also partially prevented but did not treat colitis in B27 transgenic rats. In both animal models vancomycin-imipenem most effectively prevented and treated colitis. Germfree transgenic rats reconstituted with enteric bacteria grown under anaerobic conditions had more aggressive colitis than those associated with aerobic bacteria. These results suggest that a subset of resident luminal bacteria induces colitis, but that a complex interaction of commensal aerobic and anaerobic bacteria provides the constant antigenic drive for chronic immune-mediated colonic inflammation.
常驻细菌被认为与实验性结肠炎和炎症性肠病的发病机制有关。我们研究了各种肠道细菌群体在实验性结肠炎的诱导和持续发展中的相对作用。HLA - B27转基因大鼠在预防或治疗方案中，饮用含抗生素（环丙沙星、甲硝唑或万古霉素 - 亚胺培南）的水或仅饮用普通水。小鼠在接受5%葡聚糖硫酸钠（DSS）之前或之后，同样用甲硝唑或万古霉素 - 亚胺培南进行治疗。无菌转基因大鼠用在厌氧或需氧环境中过夜培养的无特定病原体的肠道细菌进行定殖。用厌氧细菌定殖的非转基因大鼠作为阴性对照。虽然预防性使用甲硝唑可显著减轻转基因大鼠和DSS处理小鼠的结肠炎，但一旦结肠炎形成，它并无治疗益处。环丙沙星也能部分预防但不能治疗B27转基因大鼠的结肠炎。在两种动物模型中，万古霉素 - 亚胺培南预防和治疗结肠炎的效果最为显著。用在厌氧条件下生长的肠道细菌重建的无菌转基因大鼠比那些与需氧细菌相关的大鼠患更严重的结肠炎。这些结果表明，一部分常驻腔内细菌可诱导结肠炎，但共生需氧菌和厌氧菌的复杂相互作用为慢性免疫介导的结肠炎症提供了持续的抗原驱动。
