Borowitz Stephen M
Division of Pediatric Gastroenterology, Hepatology and Nutrition, University of Virginia, Charlottesville, VA, United States.
Front Pediatr. 2023 Jan 17;10:1103713. doi: 10.3389/fped.2022.1103713. eCollection 2022.
Historically, inflammatory bowel disease (IBD) was most common in North America and Europe and more common with a north-south gradient. Over the past century, there has been a marked increase in IBD in general and in childhood IBD in particular and over the past 50 years IBD has spread into the developing world. The greatest risk factor of developing IBD is an affected family member. Concordance rates between dizygotic twins is ∼4% and ∼50% in monozygotic twins, and more than half of pairs are diagnosed within 2 years of each other. Nevertheless, most patients with IBD do not have an affected family member. More than 200 genes are associated with an increased risk for IBD, but most associations are weak with odds ratios between 1.2 and 2.0 suggesting the environment plays a role. IBD is more common in urban than rural regions and is associated with "good standards" of domestic hygiene during childhood. People who migrate from areas with a low incidence to areas with a high incidence of IBD have an increased risk of developing IBD and the younger they are when they migrate, the greater their risk of developing IBD. Moreover, people who migrate from regions with a high incidence to areas with a low incidence of IBD have a decreased risk of developing IBD. Together, these findings strongly suggest particular environmental exposures occurring early in life may trigger inflammatory bowel disease in genetically susceptible individuals. The key is figuring out what those exposures might be.
从历史上看,炎症性肠病(IBD)在北美和欧洲最为常见,且呈现出从北到南发病率逐渐升高的梯度分布。在过去的一个世纪里,IBD总体发病率显著上升,尤其是儿童IBD发病率上升明显,并且在过去50年中IBD已蔓延至发展中世界。患IBD的最大风险因素是有患病的家庭成员。异卵双胞胎的IBD一致性率约为4%,同卵双胞胎则约为50%,超过半数的双胞胎在彼此确诊后的两年内被诊断出患病。然而,大多数IBD患者并没有患病的家庭成员。超过200个基因与IBD风险增加相关,但大多数关联较弱,优势比在1.2至2.0之间,这表明环境因素也起到了作用。IBD在城市地区比农村地区更为常见,并且与儿童时期“良好的”家庭卫生标准有关。从IBD低发病率地区迁移至高发病率地区的人群患IBD的风险增加,且迁移时年龄越小,患IBD的风险就越大。此外,从IBD高发病率地区迁移至低发病率地区的人群患IBD的风险降低。总之,这些发现强烈表明,生命早期发生的特定环境暴露可能会在基因易感个体中引发炎症性肠病。关键在于弄清楚这些暴露因素可能是什么。