Division of Oral Biology, College of Dentistry, The Ohio State University, Columbus, OH 43210, United States.
Brain Behav Immun. 2011 Mar;25(3):397-407. doi: 10.1016/j.bbi.2010.10.023. Epub 2010 Oct 30.
The bodies of most animals are populated by highly complex and genetically diverse communities of microorganisms. The majority of these microbes reside within the intestines in largely stable but dynamically interactive climax communities that positively interact with their host. Studies from this laboratory have shown that stressor exposure impacts the stability of the microbiota and leads to bacterial translocation. The biological importance of these alterations, however, is not well understood. To determine whether the microbiome contributes to stressor-induced immunoenhancement, mice were exposed to a social stressor called social disruption (SDR), that increases circulating cytokines and primes the innate immune system for enhanced reactivity. Bacterial populations in the cecum were characterized using bacterial tag-encoded FLX amplicon pyrosequencing. Stressor exposure significantly changed the community structure of the microbiota, particularly when the microbiota were assessed immediately after stressor exposure. Most notably, stressor exposure decreased the relative abundance of bacteria in the genus Bacteroides, while increasing the relative abundance of bacteria in the genus Clostridium. The stressor also increased circulating levels of IL-6 and MCP-1, which were significantly correlated with stressor-induced changes to three bacterial genera (i.e., Coprococcus, Pseudobutyrivibrio, and Dorea). In follow up experiments, mice were treated with an antibiotic cocktail to determine whether reducing the microbiota would abrogate the stressor-induced increases in circulating cytokines. Exposure to SDR failed to increase IL-6 and MCP-1 in the antibiotic treated mice. These data show that exposure to SDR significantly affects bacterial populations in the intestines, and remarkably also suggest that the microbiota are necessary for stressor-induced increases in circulating cytokines.
大多数动物的体内都居住着高度复杂和遗传多样的微生物群落。这些微生物大多数存在于肠道内，形成相对稳定但动态交互的顶极群落，并与宿主进行积极的相互作用。本实验室的研究表明，应激源暴露会影响微生物群落的稳定性，并导致细菌易位。然而，这些变化的生物学重要性尚不清楚。为了确定微生物组是否有助于应激诱导的免疫增强，研究人员将小鼠暴露于一种称为社交中断（SDR）的社交应激源中，该应激源会增加循环细胞因子并使先天免疫系统为增强的反应性做好准备。使用细菌标签编码 FLX 扩增子焦磷酸测序来描述盲肠中的细菌种群。应激源暴露显著改变了微生物群落的结构，尤其是在应激源暴露后立即评估微生物群落时。值得注意的是，应激源暴露降低了拟杆菌属细菌的相对丰度，而增加了梭菌属细菌的相对丰度。应激源还增加了循环中的 IL-6 和 MCP-1 水平，这与应激源诱导的三种细菌属（即粪球菌、假丁酸弧菌和多拉氏菌）的变化显著相关。在后续实验中，研究人员用抗生素混合物处理小鼠，以确定减少微生物群是否会消除应激源诱导的循环细胞因子增加。SDR 暴露未能增加抗生素处理小鼠的 IL-6 和 MCP-1。这些数据表明，SDR 暴露会显著影响肠道中的细菌种群，并且还表明微生物群是应激诱导的循环细胞因子增加所必需的。
