Department of Gastroenterology and Hepatology, Digestive Disease Institute, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.
Dig Dis. 2012;30(4):428-33. doi: 10.1159/000338148. Epub 2012 Jul 12.
To discuss a cure for IBD, one should first define the concept 'a cure'. If it is intended as the general restoration of health, this is already possible, as many current therapies do a good job in inducing long periods of remission in Crohn's disease, and colectomy can technically cure ulcerative colitis. If it is more strictly defined as the complete and permanent elimination of the cause, predisposing and permissive factors, reinstatement of normal microbial ecology and restoration of mucosal immune homeostasis, then a cure for IBD is out of reach, at least for now. Regardless of the definition, major strides have been made in attempting to cure IBD by addressing the key components of its pathogenesis: the environment (exposome), the genetic makeup (genome), the gut microbiota (microbiome) and the immune system (immunome). However, the isolated modulation of each component is insufficient to provide a cure, and different requirements may be needed depending on the stage of the disease and each patient subset. To achieve a cure, one key approach is currently missing: the integration of knowledge from all the pathogenic components. We continue to learn more and more about each component using traditional 'canonical' systems, which allow the accumulation of data without taking into consideration the other components. We are still not studying the 'omes' of IBD, we should be using 'omics' technologies that can generate a more global vision of IBD pathogenesis on which to base novel, multiple pathway-integrated therapies.
要讨论 IBD 的治愈方法,首先应该定义“治愈”的概念。如果它是指广义上的健康恢复,那么这已经成为可能,因为许多当前的治疗方法在诱导克罗恩病的长时间缓解方面做得很好,而且结肠切除术在技术上可以治愈溃疡性结肠炎。如果更严格地定义为完全和永久消除病因、易患因素和许可因素,恢复正常的微生物生态和粘膜免疫稳态,那么 IBD 的治愈方法就遥不可及,至少目前是这样。无论如何,在通过解决发病机制的关键组成部分来尝试治愈 IBD 方面已经取得了重大进展:环境(暴露组)、遗传构成(基因组)、肠道微生物群(微生物组)和免疫系统(免疫组)。然而,单独调节每个组成部分不足以提供治愈方法,并且根据疾病的阶段和每个患者亚组,可能需要不同的要求。要实现治愈,目前缺少一个关键方法:整合所有致病成分的知识。我们继续使用传统的“经典”系统了解每个组成部分的越来越多的信息,这些系统允许在不考虑其他组成部分的情况下积累数据。我们仍未研究 IBD 的“omes”,我们应该使用“omics”技术,这些技术可以生成关于 IBD 发病机制的更全面的视角,从而为新的、多途径整合的治疗方法提供基础。
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