Extreme Dysbiosis of the Microbiome in Critical Illness.
Extreme Dysbiosis of the Microbiome in Critical Illness.
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DOI：
10.1128/msphere.00199-16
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发表时间：
2016-07
期刊：
影响因子：
4.8
通讯作者：
Wischmeyer PE
中科院分区：
文献类型：
--
作者：
McDonald D;Ackermann G;Khailova L;Baird C;Heyland D;Kozar R;Lemieux M;Derenski K;King J;Vis-Kampen C;Knight R;Wischmeyer PE
危重病可能与正常的“健康促进”细菌的丧失有关，从而使促进疾病的致病细菌过度生长（生态失调），这反过来又使患者易受医院获得性感染、败血症和器官衰竭的影响。这对世界卫生具有重大影响，因为脓毒症正在成为全球死亡的主要原因，医院获得性感染导致严重疾病和费用增加。因此，迫切需要一项监测ICU患者微生物组的试验来证实和表征这一假设。我们的研究分析了115名重症受试者的微生物组，并证明了ICU入院后意外环境来源的快速生态失调。这些数据可能提供了定义靶向治疗的第一步，这些治疗可以通过益生菌或靶向多微生物合成“大便丸”纠正潜在的“促进疾病”的生态失调，从而在ICU环境中恢复健康的微生物组，以改善患者的预后。危重病被假设为与“促进健康”的肠道微生物的丧失和病原菌的过度生长（生态失调）有关。这种生态失调被认为增加了对医院感染、败血症和器官衰竭的易感性。因此，迫切需要使用非培养技术对重症监护病房（ICU）患者微生物组进行前瞻性监测的试验，以确认和表征这种生态失调。表征ICU患者的微生物组变化可以为使用微生物组特征开发诊断和治疗干预措施提供第一步。为了表征ICU患者的微生物组，我们收集了来自美国和加拿大四个中心的115名混合ICU患者的粪便，口腔和皮肤样本。在两个时间点采集样本：ICU入院后48小时内和ICU出院时或ICU第10天。根据地球微生物组计划方案进行样品收集和处理。我们应用SourceTracker通过使用Qiita评估ICU患者样本的来源组成，包括来自美国肠道项目（AGP）的样本、哺乳动物尸体分解样本、儿童（全球肠道研究）和房屋表面。我们的研究结果表明，危重病导致显著和快速的生态失调。与AGP健康对照相比，ICU患者中许多分类群显著减少，这是关键的“健康促进”生物体，并且常见已知病原体的过度生长。ICU患者样本的来源组成在很大程度上不具有预期社区类型的特征。在时间点之间和患者体内，源成分发生了显著变化。我们的初步结果显示，微生物组特征作为诊断标志物和指导ICU治疗干预的前景很好，可以重新填充正常的“促进健康”的微生物组，从而改善患者的预后。重要性危重病可能与正常的“健康促进”细菌的丧失有关，从而使促进疾病的致病细菌过度生长（生态失调），这反过来又使患者容易发生医院获得性感染、败血症和器官衰竭。这对世界卫生具有重大影响，因为脓毒症正在成为全球死亡的主要原因，医院获得性感染导致严重疾病和费用增加。因此，迫切需要一项监测ICU患者微生物组的试验来证实和表征这一假设。我们的研究分析了115名重症受试者的微生物组，并证明了ICU入院后意外环境来源的快速生态失调。这些数据可能提供了定义靶向治疗的第一步，这些治疗可以通过益生菌或靶向多微生物合成“大便丸”纠正潜在的“促进疾病”的生态失调，从而在ICU环境中恢复健康的微生物组，以改善患者的预后。Podcast：有关于这篇文章的Podcast。
Critical illness may be associated with the loss of normal, “health promoting” bacteria, allowing overgrowth of disease-promoting pathogenic bacteria (dysbiosis), which, in turn, makes patients susceptible to hospital-acquired infections, sepsis, and organ failure. This has significant world health implications, because sepsis is becoming a leading cause of death worldwide, and hospital-acquired infections contribute to significant illness and increased costs. Thus, a trial that monitors the ICU patient microbiome to confirm and characterize this hypothesis is urgently needed. Our study analyzed the microbiomes of 115 critically ill subjects and demonstrated rapid dysbiosis from unexpected environmental sources after ICU admission. These data may provide the first steps toward defining targeted therapies that correct potentially “illness-promoting” dysbiosis with probiotics or with targeted, multimicrobe synthetic “stool pills” that restore a healthy microbiome in the ICU setting to improve patient outcomes. Critical illness is hypothesized to associate with loss of “health-promoting” commensal microbes and overgrowth of pathogenic bacteria (dysbiosis). This dysbiosis is believed to increase susceptibility to nosocomial infections, sepsis, and organ failure. A trial with prospective monitoring of the intensive care unit (ICU) patient microbiome using culture-independent techniques to confirm and characterize this dysbiosis is thus urgently needed. Characterizing ICU patient microbiome changes may provide first steps toward the development of diagnostic and therapeutic interventions using microbiome signatures. To characterize the ICU patient microbiome, we collected fecal, oral, and skin samples from 115 mixed ICU patients across four centers in the United States and Canada. Samples were collected at two time points: within 48 h of ICU admission, and at ICU discharge or on ICU day 10. Sample collection and processing were performed according to Earth Microbiome Project protocols. We applied SourceTracker to assess the source composition of ICU patient samples by using Qiita, including samples from the American Gut Project (AGP), mammalian corpse decomposition samples, childhood (Global Gut study), and house surfaces. Our results demonstrate that critical illness leads to significant and rapid dysbiosis. Many taxons significantly depleted from ICU patients versus AGP healthy controls are key “health-promoting” organisms, and overgrowth of known pathogens was frequent. Source compositions of ICU patient samples are largely uncharacteristic of the expected community type. Between time points and within a patient, the source composition changed dramatically. Our initial results show great promise for microbiome signatures as diagnostic markers and guides to therapeutic interventions in the ICU to repopulate the normal, “health-promoting” microbiome and thereby improve patient outcomes. IMPORTANCE Critical illness may be associated with the loss of normal, “health promoting” bacteria, allowing overgrowth of disease-promoting pathogenic bacteria (dysbiosis), which, in turn, makes patients susceptible to hospital-acquired infections, sepsis, and organ failure. This has significant world health implications, because sepsis is becoming a leading cause of death worldwide, and hospital-acquired infections contribute to significant illness and increased costs. Thus, a trial that monitors the ICU patient microbiome to confirm and characterize this hypothesis is urgently needed. Our study analyzed the microbiomes of 115 critically ill subjects and demonstrated rapid dysbiosis from unexpected environmental sources after ICU admission. These data may provide the first steps toward defining targeted therapies that correct potentially “illness-promoting” dysbiosis with probiotics or with targeted, multimicrobe synthetic “stool pills” that restore a healthy microbiome in the ICU setting to improve patient outcomes. Podcast: A podcast concerning this article is available.