Division of Geriatric and Palliative Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
Graduate Program in Immunology, University of Michigan, Ann Arbor, Michigan, USA.
mSphere. 2019 Mar 20;4(2):e00138-19. doi: 10.1128/mSphereDirect.00138-19.
Between October 2016 and June 2017, a C57BL/6J mouse colony that was undergoing a pre- and perinatal methyl donor supplementation diet intervention to study the impact of parental nutrition on offspring susceptibility to disease was found to suffer from an epizootic of unexpected deaths. Necropsy revealed the presence of severe colitis, and further investigation linked these outbreak deaths to a strain of ribotype 027 that we term 16N203. infection (CDI) is associated with antibiotic use in humans. Current murine models of CDI rely on antibiotic pretreatment to establish clinical phenotypes. In this report, the outbreak occurs in F1 mice linked to alterations in the parental diet. The diagnosis of CDI in the affected mice was confirmed by cecal/colonic histopathology, the presence of bacteria in fecal/colonic culture, and detection of toxins. F1 mice from parents fed the methyl supplementation diet also had significantly reduced survival ( < 0.0001) compared with F1 mice from parents fed the control diet. When we tested the 16N203 outbreak strain in an established mouse model of antibiotic-induced CDI, we confirmed that this strain is pathogenic. Our serendipitous observations from this spontaneous outbreak of in association with a pre- and perinatal methyl donor diet suggest the important role that diet may play in host defense and CDI risk factors. infection (CDI) has become the leading cause of infectious diarrhea in hospitals worldwide, owing its preeminence to the emergence of hyperendemic strains, such as ribotype 027 (RT027). A major CDI risk factor is antibiotic exposure, which alters gut microbiota, resulting in the loss of colonization resistance. Current murine models of CDI also depend on pretreatment of animals with antibiotics to establish disease. The outbreak that we report here is unique in that the CDI occurred in mice with no antibiotic exposure and is associated with a pre- and perinatal methyl supplementation donor diet intervention study. Our investigation subsequently reveals that the outbreak strain that we term 16N203 is an RT027 strain, and this isolated strain is also pathogenic in an established murine model of CDI (with antibiotics). Our report of this spontaneous outbreak offers additional insight into the importance of environmental factors, such as diet, and CDI susceptibility.
2016 年 10 月至 2017 年 6 月，一个正在接受预产前甲基供体补充饮食干预以研究父母营养对后代易患疾病影响的 C57BL/6J 鼠群突然爆发了意外死亡。尸检显示存在严重的结肠炎，进一步的调查将这些爆发性死亡与我们称之为 16N203 的 027 型菌株联系起来。 感染（CDI）与人类使用抗生素有关。目前的 CDI 小鼠模型依赖于抗生素预处理来建立临床表型。在本报告中，爆发发生在与父母饮食改变有关的 F1 小鼠中。受感染小鼠的 CDI 诊断通过盲肠/结肠组织病理学、粪便/结肠培养中 的存在以及检测到 的毒素得到确认。用甲基补充饮食喂养的父母的 F1 小鼠的存活率也明显降低（<0.0001），而用对照饮食喂养的父母的 F1 小鼠的存活率则没有。当我们在已建立的抗生素诱导 CDI 小鼠模型中测试 16N203 爆发菌株时，我们证实该菌株具有致病性。我们从与预产前甲基供体饮食相关的 自发爆发中偶然观察到的结果表明，饮食可能在宿主防御和 CDI 危险因素中发挥重要作用。 感染（CDI）已成为全球医院感染性腹泻的主要原因，其主要原因是出现了高流行株，如 027 型（RT027）。CDI 的一个主要危险因素是抗生素暴露，它改变了肠道微生物群，导致定植抵抗力丧失。目前的 CDI 小鼠模型也依赖于用抗生素预处理动物来建立疾病。我们报告的这次爆发是独特的，因为 CDI 发生在没有抗生素暴露的小鼠中，并且与预产前甲基补充供体饮食干预研究有关。我们的调查随后表明，我们称之为 16N203 的爆发菌株是一种 RT027 菌株，这种分离株在已建立的 CDI 小鼠模型（使用抗生素）中也是致病性的。我们对这次自发爆发的报告提供了更多的证据，证明了环境因素（如饮食）和 CDI 易感性的重要性。
