Departments of Medicine, University of Virginia, Charlottesville.
Biology, University of Virginia, Charlottesville.
J Infect Dis. 2018 Jan 4;217(2):188-197. doi: 10.1093/infdis/jix414.
Clostridium difficile infection (CDI) is a serious threat for an aging population. Using an aged mouse model, we evaluated the effect of age and the roles of innate immunity and intestinal microbiota.
Aged (18 months) and young (8 weeks) mice were infected with C difficile, and disease severity, immune response, and intestinal microbiome were compared. The same experiment was repeated with intestinal microbiota exchange between aged and young mice before infection.
Higher mortality was observed in aged mice with weaker neutrophilic mobilization in blood and intestinal tissue and depressed proinflammatory cytokines in early infection. Microbiota exchange improved survival and early immune response in aged mice. Microbiome analysis revealed that aged mice have significant deficiencies in Bacteroidetes phylum and, specifically, Bacteroides, Alistipes, and rc4-4 genera, which were replenished by cage switching.
Microbiota-dependent alteration in innate immune response early on during infection may explain poor outcome in aged host with CDI.
艰难梭菌感染（CDI）是老龄化人口的严重威胁。本研究使用老年小鼠模型，评估了年龄的影响以及固有免疫和肠道微生物群的作用。
用艰难梭菌感染老年（18 个月）和年轻（8 周）小鼠，比较疾病严重程度、免疫反应和肠道微生物组。在感染前，进行肠道微生物群交换实验，比较老年和年轻小鼠之间的相同实验。
老年小鼠死亡率更高，血液和肠道组织中中性粒细胞动员减弱，早期感染时促炎细胞因子水平降低。菌群交换改善了老年小鼠的存活和早期免疫反应。微生物组分析显示，老年小鼠在拟杆菌门和特定的拟杆菌属、alistipes 属和 rc4-4 属存在显著缺陷，通过笼间交换得到补充。
感染早期固有免疫反应的菌群依赖性改变可能解释了 CDI 老年宿主不良预后的原因。
