Clostridioides difficile (C. difficile) is a gram-positive, spore-forming, anaerobic bacterium known to be the most common cause of hospital-acquired and antibiotic-associated diarrhea. C. difficile infection rates are on the rise worldwide and treatment options are limited, indicating a clear need for novel therapeutics. Gnotobiotic piglets are an excellent model to reproduce the acute pseudomembranous colitis (PMC) caused by C. difficile due to their physiological similarities to humans and high susceptibility to infection. Here, we established a gnotobiotic pig model of C. difficile infection and disease using a hypervirulent strain. C. difficile-infected pigs displayed classic signs of C. difficile infection, including severe diarrhea and weight loss. Inoculated pigs had severe gross and microscopic intestinal lesions. C. difficile infection caused an increase in pro-inflammatory cytokines in samples of serum, large intestinal contents, and pleural effusion. C. difficile spores and toxins were detected in the feces of inoculated animals as tested by anaerobic culture and cytotoxicity assays. Successful establishment of this model is key for future work as therapeutics can be evaluated in an environment that accurately mimics what happens in humans. The model is especially suitable for evaluating potential prophylactics and therapeutics, including vaccines and passive immune strategies.

中文翻译：

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猪难辨梭状芽孢杆菌感染及发病模型的建立

艰难梭菌 (C. difficile) 是一种革兰氏阳性、形成孢子的厌氧菌，已知是医院获得性和抗生素相关性腹泻的最常见原因。C. difficile 感染率在世界范围内呈上升趋势，治疗选择有限，这表明对新疗法的明确需求。Gnotobiotic 仔猪是复制由艰难梭菌引起的急性假膜性结肠炎 (PMC) 的极好模型，因为它们与人类的生理相似性和对感染的高度易感性。在这里，我们使用超强毒力菌株建立了艰难梭菌感染和疾病的无菌猪模型。艰难梭菌感染的猪表现出艰难梭菌感染的典型症状，包括严重腹泻和体重减轻。接种的猪有严重的肉眼和微观肠道损伤。C。艰难梭菌感染引起血清、大肠内容物和胸腔积液样本中促炎细胞因子的增加。通过厌氧培养和细胞毒性测定，在接种动物的粪便中检测到艰难梭菌孢子和毒素。成功建立该模型是未来工作的关键，因为可以在准确模拟人类发生情况的环境中评估治疗方法。该模型特别适用于评估潜在的预防和治疗方法，包括疫苗和被动免疫策略。成功建立该模型是未来工作的关键，因为可以在准确模拟人类发生情况的环境中评估治疗方法。该模型特别适用于评估潜在的预防和治疗方法，包括疫苗和被动免疫策略。成功建立该模型是未来工作的关键，因为可以在准确模拟人类发生情况的环境中评估治疗方法。该模型特别适用于评估潜在的预防和治疗方法，包括疫苗和被动免疫策略。