Mice with Inflammatory Bowel Disease are Susceptible to Clostridium difficile Infection With Severe Disease Outcomes.
Mice with Inflammatory Bowel Disease are Susceptible to Clostridium difficile Infection With Severe Disease Outcomes.
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DOI：
10.1093/ibd/izx059
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发表时间：
2018-02-15
影响因子：
4.9
通讯作者：
Feng H
中科院分区：
文献类型：
--
作者：
Zhou F;Hamza T;Fleur AS;Zhang Y;Yu H;Chen K;Heath JE;Chen Y;Huang H;Feng H
在过去的几十年中，患有炎症性肠病（IBD）的患者中艰难梭菌感染（CDI）的发病率显著增加。然而，没有野生型动物模型可用于研究这些共病疾病。我们评估了有或没有抗生素暴露的葡聚糖硫酸钠盐（DSS）诱导的结肠炎（IBD）小鼠对CDI的敏感性;我们检查了模型建立后伴随疾病的组织病理学和细胞因子反应。在健康对照小鼠中没有发生CDI，而IBD小鼠中CDI的发生率为40%;然而，在接受抗生素的IBD小鼠中，CDI的发生率为100%，并且该疾病伴随着小鼠粪便和血清中高水平的毒素。与单独感染IBD和CDI相比，感染C.艰难梭菌具有更严重的症状、毒血症、组织病理学损害和更高的死亡率。此外，几种促炎细胞因子和趋化因子在感染C.很难我们首次在动物模型中证明，患有葡聚糖硫酸钠诱导的炎症性肠病的小鼠对C.艰难梭菌感染，细菌感染导致更严重的疾病和死亡。这些发现与临床观察结果一致，因此，动物模型将使我们能够研究这些并发疾病的发病机制，并制定针对IBD和CDI合并症的治疗策略。
Over the past several decades, there has been a significant increase in the incidence of Clostridium difficile infection (CDI) in patients suffering from inflammatory bowel disease (IBD). However, a wild-type animal model is not available to study these comorbid diseases. We evaluated the susceptibility to CDI of mice with dextran sulfate sodium salt (DSS)-induced colitis (IBD mice) with or without antibiotic exposure; we examined the histopathology and cytokine response in the concomitant diseases after the model was created. No CDI occurs in healthy control mice, wherease the incidence of CDI in IBD mice is 40%; however, in IBD mice that received antibiotics, the incidence of CDI is 100% and the disease is accompanied by high levels of toxins in the mouse feces and sera. Compared to IBD and CDI alone, those IBD mice infected with C. difficile have more severe symptoms, toxemia, histopathological damage, and higher mortality. Moreover, several proinflammatory cytokines and chemokines are significantly elevated in the colon tissues from IBD mice infected with C. difficile. We, for the first time, demonstrate in an animal model that mice with dextran sulfate sodium induced-inflammatory bowel disease are significantly more susceptible to C. difficile infection, and that the bacterial infection led to more severe disease and death. These findings are consistent with clinical observations, thus, the animal model will permit us to study the pathogenesis of these concurrent diseases and to develop therapeutic strategies against the comorbidity of IBD and CDI.
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