Clostridioides difficile has emerged as a noteworthy pathogen in patients with inflammatory bowel disease (IBD). Concurrent IBD and CDI is associated with increased morbidity and mortality compared to CDI alone. IBD is associated with alterations of the gut microbiota, an important mediator of colonization resistance to C. difficile. Here, we describe and utilize a mouse model to explore the role of intestinal inflammation in susceptibility to C. difficile colonization and subsequent disease severity in animals with underlying IBD. Helicobacter hepaticus, a normal member of the mouse gut microbiota, was used to trigger inflammation in the distal intestine akin to human IBD in mice that lack intact IL-10 signaling. Development of IBD resulted in a distinct intestinal microbiota community compared to non-IBD controls. We demonstrate that in this murine model, IBD was sufficient to render mice susceptible to C. difficile colonization. Mice with IBD were persistently colonized by C. difficile, while genetically identical non-IBD controls were resistant to C. difficile colonization. Concomitant IBD and CDI was associated with significantly worse disease than unaccompanied IBD. IL-10-deficient mice maintained gut microbial diversity and colonization resistance to C. difficile in experiments utilizing an isogenic mutant of H. hepaticus that does not trigger intestinal inflammation. These studies in mice demonstrate that the IBD-induced microbiota is sufficient for C. difficile colonization and that this mouse model requires intestinal inflammation for inducing susceptibility to CDI in the absence of other perturbations, such as antibiotic treatment.

中文翻译：

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肠道炎症和与炎症性肠病相关的肠道菌群改变使小鼠易患梭状芽胞杆菌艰难的定居和感染

艰难梭菌已成为炎症性肠病（IBD）患者的重要病原体。与单独的CDI相比，IBD和CDI并发会增加发病率和死亡率。IBD与肠道菌群的改变有关，肠道菌群是艰难梭菌定植抗性的重要介体。在这里，我们描述并利用小鼠模型来探索肠道炎症在难辨梭状芽孢杆菌定植的敏感性以及随后患有潜在IBD的动物中疾病的严重性中的作用。肝幽门螺杆菌小鼠肠道菌群的正常成员，一种缺乏完整的IL-10信号传导的小鼠，在类似于人IBD的远端肠中引发炎症。与非IBD对照相比，IBD的发展导致了独特的肠道菌群群落。我们证明，在这种鼠模型中，IBD足以使小鼠易患艰难梭菌定植。具有IBD的小鼠被艰难梭菌持续定居，而遗传上相同的非IBD对照对艰难梭菌定植具有抗性。与无伴奏的IBD相比，伴随的IBD和CDI与明显更差的疾病相关。IL-10缺陷小鼠维持肠道微生物多样性和对艰难梭菌的定植性在利用不会触发肠道炎症的肝嗜血杆菌的同基因突变体进行的实验中。这些在小鼠中的研究表明，IBD诱导的微生物群足以用于艰难梭菌定殖，并且该小鼠模型需要肠道炎症以诱导对CDI的易感性，而没有其他干扰（例如抗生素治疗）。