The gut microbiome alters immunophenotype and survival from sepsis
The gut microbiome alters immunophenotype and survival from sepsis
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DOI：
10.1096/fj.201802188r
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发表时间：
2019-10-01
期刊：
影响因子：
4.8
通讯作者：
Coopersmith, Craig M.
中科院分区：
文献类型：
--
作者：
Fay, Katherine T.;Klingensmith, Nathan J.;Coopersmith, Craig M.
微生物组越来越多地参与免疫调节和败血症的死亡率。从不同供应商获得具有相同遗传背景但不同微生物组的小鼠，并在盲肠结扎和穿孔（CLP）后进行分析。从粪便测量的微生物组的β多样性证明了杰克逊实验室（Jax; Bar Harbor，ME，USA）和查尔斯河实验室（CR;威尔明顿，MA，USA）C57/B6小鼠之间的显著差异。Jax小鼠CLP后7天死亡率为90%，而CR小鼠的死亡率为53%。供应商的差异与免疫表型改变相关，在脓毒症CR小鼠中，脾IFN-γ（+）CD 4（+）T细胞、效应记忆CD 4（+）T细胞和中枢记忆CD 4（+）T细胞增加，派伊尔集合淋巴结效应记忆CD 4（+）T细胞增加。为了确定微生物群的差异是否是造成这些差异的原因，Jax和CR小鼠共同饲养3周，之后它们呈现出相似的微生物群组成。与Jax小鼠相比，共同饲养的小鼠在CLP后的存活率有所提高，并且无论其来源的供应商如何，其存活率相似。脓毒症Jax和CR小鼠之间的免疫表型的所有差异消失后共住房。这些发现表明，微生物组在败血症的生存和宿主免疫反应中起着至关重要的作用，并代表了治疗干预的潜在目标。Fay，K. T.，Klingensmith，N. J.，陈春W.，张伟，Sun，Y.，Morrow，K. N.，梁志，Burd，E. M.，福特，M. L.，库珀史密斯角M.肠道微生物组改变免疫表型和脓毒症的存活率。
The microbiome is increasingly implicated in immune regulation and mortality from sepsis. Mice with identical genetic backgrounds but distinct microbiomes were obtained from different vendors and analyzed following cecal ligation and puncture (CLP). beta diversity of the microbiome measured from feces demonstrated significant differences between The Jackson Laboratory (Jax; Bar Harbor, ME, USA) and Charles River Laboratories (CR; Wilmington, MA, USA) C57/B6 mice. Jax mice had 7-d mortality of 90% following CLP, whereas CR mice had a mortality of 53%. Differences in vendor were associated with altered immunophenotype with increased splenic IFN-gamma(+)CD4(+) T cells, effector memory CD4(+) T cells, and central memory CD4(+) T cells and increased Peyer's patch effector memory CD4(+) T cells in septic CR mice. To determine whether differences in the microbiome were responsible for these differences, Jax and CR mice were cohoused for 3 wk, after which they assumed a similar microbiota composition. Cohoused mice had improved survival following CLP compared to Jax mice and had similar survival regardless of their vendor of origin. All differences in immunophenotype between septic Jax and CR mice disappeared following cohousing. These findings suggest that the microbiome plays a crucial role in survival and the host immune response from sepsis and represents a potential target for therapeutic intervention.-Fay, K. T., Klingensmith, N. J., Chen, C.-W., Zhang, W., Sun, Y., Morrow, K. N., Liang, Z., Burd, E. M., Ford, M. L., Coopersmith, C. M. The gut microbiome alters immunophenotype and survival from sepsis.