Division of Computational and Systems Medicine, Department of Surgery and Cancer, Imperial College, London, United Kingdom.
Department of Biomedical Engineering, University of Virginia School of Medicine, Charlottesville, VA, United States of America.
PLoS Pathog. 2018 May 23;14(3):e1007083. doi: 10.1371/journal.ppat.1007083. eCollection 2018 Mar.
Campylobacter infections are among the leading bacterial causes of diarrhea and of 'environmental enteropathy' (EE) and growth failure worldwide. However, the lack of an inexpensive small animal model of enteric disease with Campylobacter has been a major limitation for understanding its pathogenesis, interventions or vaccine development. We describe a robust standard mouse model that can exhibit reproducible bloody diarrhea or growth failure, depending on the zinc or protein deficient diet and on antibiotic alteration of normal microbiota prior to infection. Zinc deficiency and the use of antibiotics create a niche for Campylobacter infection to establish by narrowing the metabolic flexibility of these mice for pathogen clearance and by promoting intestinal and systemic inflammation. Several biomarkers and intestinal pathology in this model also mimic those seen in human disease. This model provides a novel tool to test specific hypotheses regarding disease pathogenesis as well as vaccine development that is currently in progress.
空肠弯曲菌感染是全球范围内导致腹泻和“环境肠病”（EE）及生长障碍的主要细菌性病因之一。然而，由于缺乏一种廉价的、用于研究弯曲菌肠道疾病的小型动物模型，因此严重限制了对其发病机制、干预措施或疫苗开发的理解。我们描述了一种可靠的标准小鼠模型，该模型可根据锌缺乏或蛋白缺乏饮食以及在感染前通过抗生素改变正常菌群，表现出可重复的血性腹泻或生长障碍。锌缺乏和抗生素的使用为弯曲菌感染创造了一个定殖的小生境，通过缩小这些小鼠清除病原体的代谢灵活性，并促进肠道和全身炎症，从而促进感染的建立。该模型中的几种生物标志物和肠道病理学也类似于人类疾病中观察到的那些。该模型为目前正在进行的有关疾病发病机制和疫苗开发的特定假设提供了一种新的工具。
