Fecal microbiota transplant rescues mice from human pathogen mediated sepsis by restoring systemic immunity
Fecal microbiota transplant rescues mice from human pathogen mediated sepsis by restoring systemic immunity
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DOI：
10.1038/s41467-020-15545-w
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发表时间：
2020-05-11
影响因子：
16.6
通讯作者：
Alverdy, John C.
中科院分区：
文献类型：
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作者：
Kim, Sangman M.;DeFazio, Jennifer R.;Alverdy, John C.
脓毒症导致的死亡仍然是重症监护病房重症患者的持续威胁，其特点是多药耐药卫生保健相关病原体定植。在这里，我们报告了从致死性脓毒症患者中分离出的确定的四成员病原体群落引起的小鼠脓毒症与宿主转录组中清除病原体所需的关键元件的系统性抑制和丁酸盐表达的降低有关。更具体地说，这些病原体直接抑制干扰素调节因子3。粪便微生物群移植（FMT）通过干扰素调节因子3依赖的方式恢复宿主免疫，从而增强病原体清除，从而逆转致命败血症的进程。这种保护作用与产生丁酸盐的拟杆菌门的扩张有关。综上所述，这些结果表明粪便微生物群移植可能是与免疫抑制相关的败血症的一种治疗选择。多药耐药病原体引起的脓毒症是重症监护病房中最常见的死亡原因。在这里，作者报告了粪便微生物群移植（FMT）可以拯救从重症患者粪便中分离的病原体致死性败血症的小鼠，并表明FMT逆转了病原体群落诱导的免疫抑制作用。
Death due to sepsis remains a persistent threat to critically ill patients confined to the intensive care unit and is characterized by colonization with multi-drug-resistant healthcare-associated pathogens. Here we report that sepsis in mice caused by a defined four-member pathogen community isolated from a patient with lethal sepsis is associated with the systemic suppression of key elements of the host transcriptome required for pathogen clearance and decreased butyrate expression. More specifically, these pathogens directly suppress interferon regulatory factor 3. Fecal microbiota transplant (FMT) reverses the course of otherwise lethal sepsis by enhancing pathogen clearance via the restoration of host immunity in an interferon regulatory factor 3-dependent manner. This protective effect is linked to the expansion of butyrate-producing Bacteroidetes. Taken together these results suggest that fecal microbiota transplantation may be a treatment option in sepsis associated with immunosuppression. Sepsis due to multidrug resistant pathogens is the most common cause of death in intensive care units. Here, the authors report that fecal microbiota transplant (FMT) can rescue mice from lethal sepsis of pathogens isolated from stool of a critically ill patient and show that FMT reverses the immunosuppressive effect induced by the pathogen community.