Changes in Cecal Microbiota and Mucosal Gene Expression Revealed New Aspects of Epizootic Rabbit Enteropathy

Epizootic Rabbit Enteropathy (ERE) is a severe disease of unknown aetiology that mainly affects post-weaning animals. Its incidence can be prevented by antibiotic treatment suggesting that bacterial elements are crucial for the development of the disease. Microbial dynamics and host responses during the disease were studied. Cecal microbiota was characterized in three rabbit groups (ERE-affected, healthy and healthy pretreated with antibiotics), followed by transcriptional analysis of cytokines and mucins in the cecal mucosa and vermix by q-rtPCR. In healthy animals, cecal microbiota with or without antibiotic pretreatment was very similar and dominated by Alistipes and Ruminococcus. Proportions of both genera decreased in ERE rabbits whereas Bacteroides, Akkermansia and Rikenella increased, as well as Clostridium, γ-Proteobacteria and other opportunistic and pathogenic species. The ERE group displayed remarkable dysbiosis and reduced taxonomic diversity. Transcription rate of mucins and inflammatory cytokines was very high in ERE rabbits, except IL-2, and its analysis revealed the existence of two clearly different gene expression patterns corresponding to Inflammatory and (mucin) Secretory Profiles. Furthermore, these profiles were associated to different bacterial species, suggesting that they may correspond to different stages of the disease. Other data obtained in this work reinforced the notion that ERE morbidity and mortality is possibly caused by an overgrowth of different pathogens in the gut of animals whose immune defence mechanisms seem not to be adequately responding.

兔流行性肠病（Epizootic Rabbit Enteropathy，ERE）是一种病因未明的重症疾病，主要侵害断奶后幼兔。该病的发生可通过抗生素治疗得到有效预防，这提示细菌组分在疾病发生发展中发挥关键作用。本研究针对疾病进程中的微生物动态变化与宿主应答反应展开了系统探究：研究人员首先对三组家兔（ERE感染组、健康对照组及经抗生素预处理的健康对照组）的盲肠微生物群进行特征解析，随后通过定量实时聚合酶链反应（qRT-PCR）对盲肠黏膜与蚓突组织中的细胞因子及黏蛋白开展转录分析。在健康家兔中，无论是否经过抗生素预处理，其盲肠微生物群均极为相似，且以拟杆菌属（Alistipes）和瘤胃球菌属（Ruminococcus）为优势菌属。ERE感染家兔体内，上述两个菌属的相对丰度均显著下降，而拟杆菌属（Bacteroides）、嗜黏蛋白阿克曼菌属（Akkermansia）、里肯杆菌属（Rikenella）、梭菌属（Clostridium）、γ-变形菌门（γ-Proteobacteria）以及其他机会致病菌与病原菌的相对丰度则明显升高。ERE感染组家兔呈现出显著的菌群失调状态，且分类学多样性显著降低。ERE感染家兔体内的黏蛋白与炎症细胞因子转录水平普遍极高，仅白细胞介素-2（IL-2）除外；转录分析结果显示，存在两种界限分明的基因表达模式，分别对应炎症型特征谱与（黏蛋白）分泌型特征谱。此外，这两种特征谱与不同的细菌类群存在关联，提示其可能对应疾病的不同发展阶段。本研究获取的其他数据进一步佐证了上述观点：ERE的发病率与死亡率可能源于动物肠道内多种病原菌的过度增殖，而此时宿主的免疫防御机制未能做出有效应答。