Disorders of a modern lifestyle: reconciling the epidemiology of inflammatory bowel diseases
Disorders of a modern lifestyle: reconciling the epidemiology of inflammatory bowel diseases
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DOI：
10.1136/gut.2007.122143
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发表时间：
2008-09-01
期刊：
影响因子：
24.5
通讯作者：
Shanahan, Fergus
中科院分区：
文献类型：
--
作者：
Bernstein, Charles N.;Shanahan, Fergus
很少有人会质疑，在过去十年中，克罗恩病和溃疡性结肠炎遗传风险因素的发现已经改变了我们对炎症性肠病（IBD）的看法。也许最重要的信息是，大部分由基因决定的风险在于宿主如何解释其微生物环境。1-3然而，环境因素的首要作用已经从几个来源中得到了证明;特别是，对基因相同的双胞胎的研究显示，克罗恩病（50%）和溃疡性结肠炎（10%）的一致率相对较低，而且在许多国家，这两种疾病的发生频率在一段太短的时间内增加，以至于不涉及人口基因库的显著变化。4 IBD的环境或生活方式危险因素是什么？它们是如何与遗传易感性相勾结的？幽门螺杆菌和消化性溃疡的教训是，一些慢性疾病的解决方案不能通过单独研究人类宿主来找到。相反，答案可能在于与微生物环境的界面。一个更令人清醒的教训是，传统的流行病学研究未能认识到消化性溃疡是由一种传染性因子引起的。为什么不同的流行病学观察结果没有发现这种联系，也没有引导医学科学家得出这个结论？IBD（或其子集）是否可能是由感染因子引起的，有待鉴别？或者宿主易感性和微生物环境之间的关系更微妙？虽然这些疾病的复杂性和异质性肯定是造成这种困境的部分原因，但似乎有理由问，几十年的流行病学研究是否
Few would contest that advances in uncovering genetic risk factors for Crohn’s disease and ulcerative colitis over the past decade have changed the way we think about inflammatory bowel diseases (IBDs). Perhaps the most important message has been that much of the genetically determined risk lies in how the host interprets its microbial environment. 1–3 However, the primacy of environmental factors was already evident from several sources; notably, studies of genetically identical twins showing a relatively low concordance rate for both Crohn’s disease (, 50%) and ulcerative colitis (, 10%), and the increased frequency of both disorders in many countries during a period too short to involve significant changes in the population gene pool. 4 What are the environmental or lifestyle risk factors for IBD? How do they collude with genetic susceptibility?The lesson of Helicobacter pylori and peptic ulcer disease was that the solution to some chronic disorders cannot be found by studying the human host alone. Rather, the answer may lie at the interface with the microbial environment. A more sobering lesson was the failure of conventional epidemiological studies to recognise that peptic ulcer disease is caused by a transmissible agent. How did disparate epidemiological observations miss this association and fail to guide medical scientists toward this conclusion? Could IBDs (or a subset thereof) be due to an infectious agent, waiting to be identified? Or is the relationship between host susceptibility and the microbial environment a more subtle one? While the complexity and heterogeneity of these diseases surely accounts for some of this dilemma, it seems reasonable to ask whether several decades of epidemiological studies have