Pineton de Chambrun Guillaume, Colombel Jean-Frédéric, Poulain Daniel, Darfeuille-Michaud Arlette
Clinic of Digestive Disorders and Nutrition, Hôpital Claude Huriez, CHRU Lille, France.
Curr Opin Gastroenterol. 2008 Jul;24(4):440-7. doi: 10.1097/MOG.0b013e3283023be5.
Infectious agents are still thought to be involved in the origin of inflammatory bowel disease. The focus in recent years has been more on Mycobacterium avium subsp paratuberculosis, adherent-invasive Escherichia coli or yeasts.
A metaanalysis has shown a significant association of M. avium subsp paratuberculosis and Crohn's disease and a large randomized placebo-controlled trial reported an absence of sustained beneficial effects of combined antibiotic therapy on remission of active Crohn's disease. Adherent-invasive E. coli adhere via type 1 pili to carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6), abnormally expressed by intestinal epithelial cells in Crohn's disease patients. Both colonization of the ileal mucosa and stimulation of ileal epithelial cells by tumour necrosis factor-alpha induce overexpression of CEACAM6, leading to an amplification loop of colonization and inflammation. Anti-Saccharomyces cerevisiae mannan antibodies are the most prevalent serologic marker in Crohn's disease. Major oligomannose epitopes supporting antibody formation are expressed by Candida albicans in human tissues, suggesting that a loss of tolerance to C. albicans could lead to antibody formation in a subset of Crohn's disease patients who are genetically predisposed.
M. avium subsp paratuberculosis, adherent-invasive E. coli and Candida are good candidates for an infectious aetiology of Crohn's disease on the basis of genetic susceptibility, which relates to impaired function in the defence against intracellular bacteria.
感染因子仍被认为与炎症性肠病的发病有关。近年来的研究重点更多地放在了副结核分枝杆菌、黏附侵袭性大肠杆菌或酵母菌上。
一项荟萃分析表明副结核分枝杆菌与克罗恩病之间存在显著关联,一项大型随机安慰剂对照试验报告联合抗生素治疗对活动性克罗恩病的缓解没有持续的有益效果。黏附侵袭性大肠杆菌通过1型菌毛黏附于癌胚抗原相关细胞黏附分子6(CEACAM6),而在克罗恩病患者的肠道上皮细胞中该分子表达异常。回肠黏膜定植以及肿瘤坏死因子-α对回肠上皮细胞的刺激均会诱导CEACAM6的过表达,从而导致定植和炎症的放大循环。抗酿酒酵母甘露聚糖抗体是克罗恩病中最常见的血清学标志物。白色念珠菌在人体组织中表达支持抗体形成的主要低聚甘露糖表位,这表明对白色念珠菌的耐受性丧失可能导致一部分具有遗传易感性的克罗恩病患者体内形成抗体。
基于遗传易感性,副结核分枝杆菌、黏附侵袭性大肠杆菌和念珠菌是克罗恩病感染病因的有力候选因素,而遗传易感性与细胞内细菌防御功能受损有关。