Department of Pharmacology, University of South Alabama, Mobile, AL, USA.
Division of Critical Care Medicine, Cincinnati Children's Hospital Medical Center and Cincinnati Children's Research Foundation, 3333 Burnet Avenue, Cincinnati, OH, 45229, USA.
Mol Diagn Ther. 2017 Oct;21(5):525-537. doi: 10.1007/s40291-017-0282-z.
Sepsis remains one of the leading causes of death in the USA and it is expected to get worse as the population ages. Moreover, the standard of care, which recommends aggressive treatment with appropriate antibiotics, has led to an increase in multiple drug-resistant organisms. There is a dire need for the development of new antibiotics, improved antibiotic stewardship, and therapies that treat the host response. Development of new sepsis therapeutics has been a disappointment as no drugs are currently approved to treat the various complications from sepsis. Much of the failure has been blamed on animal models that do not accurately reflect the course of the disease. However, recent improvements in metabolomic, transcriptomic, genomic, and proteomic platforms have allowed for a broad-spectrum look at molecular changes in the host response using clinical samples. Integration of these multi-omic datasets allows researchers to perform systems biology approaches to identify novel pathophysiology of the disease. In this review, we highlight what is currently known about sepsis and how integrative omics has identified new diagnostic and predictive models of sepsis as well as novel mechanisms. These changes may improve patient care as well as guide future preclinical analysis of sepsis.
脓毒症仍然是美国主要的死亡原因之一,随着人口老龄化,预计情况会变得更糟。此外,推荐使用适当抗生素进行积极治疗的标准治疗方法导致了多种耐药生物的增加。迫切需要开发新的抗生素、改善抗生素管理以及针对宿主反应的治疗方法。新的脓毒症治疗方法的开发令人失望,因为目前没有药物被批准用于治疗脓毒症的各种并发症。造成这种情况的主要原因归咎于动物模型,这些模型不能准确反映疾病的进程。然而,代谢组学、转录组学、基因组学和蛋白质组学平台的最新进展使得可以使用临床样本对宿主反应的分子变化进行广谱观察。整合这些多组学数据集可使研究人员能够进行系统生物学方法,以确定疾病的新病理生理学。在这篇综述中,我们重点介绍了目前对脓毒症的了解,以及整合组学如何确定脓毒症的新诊断和预测模型以及新的机制。这些变化可能会改善患者的护理,指导未来脓毒症的临床前分析。