Characterization of the circulating microbiome in acute-on-chronic liver failure associated with hepatitis B
Characterization of the circulating microbiome in acute-on-chronic liver failure associated with hepatitis B
复制标题
乙型肝炎相关慢加急性肝衰竭的循环微生物组特征
DOI：
10.1111/liv.14097
复制
发表时间：
2019-07-01
影响因子：
6.7
通讯作者：
Shi, Yu
中科院分区：
文献类型：
--
作者：
Zhang, Yi;Zhao, Ruihong;Shi, Yu
背景
乙型肝炎相关慢加急性肝衰竭（HB - ACLF）患者可能存在循环微生物负荷增加的情况。本研究旨在评估循环微生物负荷及组成，并探究循环微生物组与HB - ACLF患者的全身炎症（SI）及临床结局之间的关联。
方法
对50例HB - ACLF患者、23例健康对照者以及25例代偿性肝硬化（C - LC）患者的血浆进行趋化因子/细胞因子和细菌DNA分析，并通过16S rDNA焦磷酸测序进一步分析。进行线性判别分析效应量（LEfSe）和推断宏基因组学分析。
结果
与对照组相比，HB - ACLF患者的循环细菌DNA显著增加。HB - ACLF患者的整体微生物多样性显著降低。与对照组相比，HB - ACLF患者富含莫拉菌科、硫单胞菌属、丛毛单胞菌属和伯克霍尔德菌科，但放线菌门、异常球菌 - 栖热菌门、α - 变形菌纲、黄单胞菌科和肠杆菌科减少。网络分析显示，在HB - ACLF患者中伯克霍尔德菌科与趋化因子IP - 10呈直接正相关。普雷沃氏菌科的相对丰度可独立预测28天死亡率。推断的功能宏基因组学预测具有与甲烷、丙氨酸、天冬氨酸、谷氨酸、嘧啶、嘌呤和能量代谢相关基因的细菌富集。
结论
HB - ACLF患者表现出循环微生物负荷增加、微生物组组成改变以及微生物组功能转变。循环微生物群的改变与HB - ACLF患者的全身炎症和临床结局相关。
Background Patients with hepatitis B-related acute-on-chronic liver failure (HB-ACLF) may have an increased circulating microbial burden. This study aimed to assess circulating microbial load and composition and to explore the association between the circulating microbiome and both systemic inflammation (SI) and clinical outcome in HB-ACLF. Methods Plasma from 50 HB-ACLF patients, 23 healthy controls and 25 patients with compensated liver cirrhosis (C-LC) was analysed for chemokines/cytokines and bacterial DNA and further analysed by 16S rDNApyrosequencing. Linear discriminant analysis effect size (LEfSe) and inferred metagenomics analyses were performed. Results The circulating bacterial DNA was significantly increased in HB-ACLF patients compared to that in the control groups. The overall microbial diversity was significantly decreased in HB-ACLF patients. HB-ACLF patients were enriched with Moraxellaceae, Sulfurovum, Comamonas and Burkholderiaceae but were depleted in Actinobacteria, Deinococcus-Thermus, Alphaproteobacteria, Xanthomonadaceae and Enterobacteriaceae compared to controls. Network analysis revealed a direct positive correlation between Burkholderiaceae and chemokine IP-10 in HB-ACLF patients. The relative abundance of Prevotellaceae independently predicted 28-day mortality. Inferred functional metagenomics predicted an enrichment of bacteria with genes related to methane, alanine, aspartate, glutamate, pyrimidine, purine and energy metabolism. Conclusions HB-ACLF patients display increased circulating microbial burden, altered microbiome composition and a shift in microbiome functionality. The alteration in circulating microbiota is associated with SI and clinical outcome in HB-ACLF.