Department of Intensive Care Unit, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
Department of Pathophysiology, Guangdong Provincial Key Laboratory of Proteomics, Southern Medical University, Guangzhou, China.
FASEB J. 2019 Nov;33(11):12299-12310. doi: 10.1096/fj.201900398RR. Epub 2019 Aug 28.
Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to microbial infection. For decades, the potential role of gut microbiota in sepsis pathogenesis has been revealed. However, the systemic and functional link between gut microbiota and sepsis has remained unexplored. To address this gap in knowledge, we carried out systematic analyses on clinical stool samples from patients with sepsis, including 16S rDNA sequencing, metabolomics, and metaproteomics analyses. In addition, we performed fecal microbiota transplantation from human to mice to validate the roles of gut microbiota on sepsis progression. We found that the composition of gut microbiota was significantly disrupted in patients with sepsis compared with healthy individuals. Besides, the microbial functions were significantly altered in septic feces as identified by metabolomics and metaproteomics analyses. Interestingly, mice that received septic feces exhibited more severe hepatic inflammation and injury than mice that received healthy feces after cecal ligation and puncture. Finally, several strains of intestinal microbiota and microbial metabolites were corelated with serum total bilirubin levels in patients with sepsis. Taken together, our data indicated that sepsis development is associated with the disruption of gut microbiota at both compositional and functional levels, and such enteric dysbiosis could promote organ inflammation and injury during sepsis.-Liu, Z., Li, N., Fang, H., Chen, X., Guo, Y., Gong, S., Niu, M., Zhou, H., Jiang, Y., Chang, P., Chen, P. Enteric dysbiosis is associated with sepsis in patients.
脓毒症是一种危及生命的器官功能障碍,由宿主对微生物感染的失调反应引起。几十年来,肠道微生物群在脓毒症发病机制中的潜在作用已经被揭示。然而,肠道微生物群与脓毒症之间的系统和功能联系仍未得到探索。为了解决这一知识空白,我们对脓毒症患者的临床粪便样本进行了系统分析,包括 16S rDNA 测序、代谢组学和宏蛋白质组学分析。此外,我们进行了来自人类到小鼠的粪便微生物群移植,以验证肠道微生物群对脓毒症进展的作用。我们发现,与健康个体相比,脓毒症患者的肠道微生物群组成明显紊乱。此外,通过代谢组学和宏蛋白质组学分析,我们发现脓毒症粪便中的微生物功能也发生了显著改变。有趣的是,与接受健康粪便的小鼠相比,接受脓毒症粪便的小鼠在盲肠结扎和穿刺后表现出更严重的肝炎症和损伤。最后,一些肠道微生物群菌株和微生物代谢物与脓毒症患者的血清总胆红素水平相关。总之,我们的数据表明,脓毒症的发展与肠道微生物群在组成和功能水平上的破坏有关,这种肠道失调可能会在脓毒症期间促进器官炎症和损伤。