Balfour Sartor R
Department of Medicine, Division of Gastroenterology and Hepatology, University of North Carolina, Chapel Hill, NC 27599, USA.
J Clin Gastroenterol. 2007 May-Jun;41 Suppl 1:S37-43. doi: 10.1097/MCG.0b013e31802db364.
Microbial agents are implicated in each of the most prevalent etiologic hypotheses of Crohn's disease. Although chronic infection with a specific, persistent pathogen cannot be excluded, it is more likely that Crohn's disease is caused by an overly aggressive immune response to normal commensal enteric bacteria. The complex, predominantly anaerobic microbiota in the distal ileum and colon provide a constant source of antigens and adjuvants that stimulate chronic immune-mediated inflammation in genetically susceptible hosts. Host genetic susceptibility in the form of defective mucosal barrier function, bacterial killing or processing can lead to enhanced exposure to luminal bacteria and their immunologically active components, whereas defective immunoregulation can lead to lack of appropriate immunosuppression. Either process can lead to overly aggressive T-cell responses to normal bacteria that causes tissue damage. Transient infection with pathogenic organisms could serve as environmental triggers to initiate inflammatory responses that are perpetuated in susceptible hosts by commensal microbial antigens. In addition, commensal bacteria such as Escherichia coli recovered from the ileum of patients with recurrent Crohn's disease after resection can contain virulence factors that mediate epithelial attachment, invasion, and resistance to killing. Finally, Western diet, antibiotic use, hygiene, and public health practices may have altered the balance of beneficial versus aggressive microbial species. Crohn's disease patients exhibit enhanced humoral and T-cell responses to common commensal bacterial and fungal antigens. These observations may help identify clinically relevant patient subsets and suggest novel therapeutic approaches to restore a beneficial balance of enteric microbiota, enhanced microbial killing, and inhibit aggressive T-cell responses to microbial antigens.
微生物制剂与克罗恩病最普遍的病因假说均有关联。虽然不能排除由特定的持续性病原体引起的慢性感染，但克罗恩病更有可能是由对正常共生肠道细菌的过度免疫反应所致。回肠末端和结肠中复杂的、主要为厌氧的微生物群提供了持续的抗原和佐剂来源，刺激基因易感宿主发生慢性免疫介导的炎症。以黏膜屏障功能缺陷、细菌杀伤或处理缺陷形式存在的宿主遗传易感性，可导致对肠腔细菌及其免疫活性成分的暴露增加，而免疫调节缺陷可导致缺乏适当的免疫抑制。任何一个过程都可能导致T细胞对正常细菌产生过度免疫反应，进而造成组织损伤。致病性生物体的短暂感染可作为环境触发因素，引发炎症反应，并通过共生微生物抗原在易感宿主中持续存在。此外，从复发性克罗恩病患者切除术后的回肠中分离出的共生细菌，如大肠杆菌，可能含有介导上皮附着、侵袭和抗杀伤的毒力因子。最后，西方饮食、抗生素使用、卫生和公共卫生习惯可能改变了有益微生物与侵袭性微生物种类之间的平衡。克罗恩病患者对常见共生细菌和真菌抗原表现出增强的体液和T细胞反应。这些观察结果可能有助于识别临床相关的患者亚群，并提出恢复肠道微生物群有益平衡、增强微生物杀伤以及抑制对微生物抗原的过度T细胞反应的新治疗方法。
