Gut dysbiosis in acute-on-chronic liver failure and its predictive value for mortality

Gut dysbiosis in acute-on-chronic liver failure and its predictive value for mortality
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慢加急性肝衰竭中的肠道菌群失调及其对死亡率的预测价值

DOI:
10.1111/jgh.12932
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发表时间:
2015-09-01
影响因子:
4.1
通讯作者:
Li, Lanjuan
Li, Lanjuan
中科院分区:
医学3区
文献类型:
--
作者:
Chen, Yanfei;Guo, Jing;Li, Lanjuan

文献摘要

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背景肠道细菌移位在慢加急性肝衰竭(ACLF)的病理生理中起重要作用。然而,在这方面,ACLF患者的肠道菌群失调在以往的研究中并没有被广泛报道,目的本研究对ACLF患者的粪便菌群进行了表征,并分析了肠道菌群在疾病期间的时间稳定性。(42例患者在首次访视后4周内接受了随访,用于纵向研究)结果ACLF组与正常对照组比较,差异有显著性(P <0.05),ACLF组与正常对照组比较,差异有显著性(P <0.05)。ACLF的总体微生物多样性和丰富度显着低于对照。ACLF患者具有较低丰度的拟杆菌科、瘤胃球菌科和毛螺菌科,但较高丰度的巴氏杆菌科、链球菌科和肠球菌科。ACLF合并肝性脑病患者毛螺菌相对丰度明显降低。ACLF发病后,肠道菌群在短期内保持相对稳定。抗生素的使用仅对肠道微生物群产生中度影响。巴氏杆菌科相对丰度和终末期肝病模型评分是预测死亡率的独立因素。网络分析比较显示,强大的相关性之间的特定细菌家族(瘤胃球菌科和毛螺菌科)和炎症细胞因子(白细胞介素[IL]-6,肿瘤坏死因子α,IL-2)ACLF patients.ConclusionsThese数据表明肠道生态失调ACLF和其预测价值的死亡率。因此,这些结果开辟了设计诊断生物标志物和靶向益生菌以降低ACLF死亡率的可能性。
BackgroundBacterial translocation from the gut plays an important role in the pathophysiology of acute-on-chronic liver failure (ACLF). However, gut dysbiosis in ACLF was not widely documented in previous studies.AimThis research characterized the fecal microbiota in patients with ACLF and analyzed the temporal stability of gut microbiota during illness.MethodsFecal microbiota of 79 ACLF patients (42 patients were followed in the next 4 weeks after the first visit for longitudinal study) and 50 healthy controls was analyzed by 16S ribosomal DNA pyrosequencing.ResultsThere was a marked difference between the ACLF group and the control group. The overall microbial diversity and richness were significantly lower in ACLF than in controls. ACLF patients had lower abundance of Bacteroidaceae, Ruminococcaceae, and Lanchnospiraceae, but higher abundance of Pasteurellaceae, Streptococcaceae, and Enterecoccaceae. The relative abundance of Lachnospiraceae was obviously decreased in ACLF patients with hepatic encephalopathy. The gut microbiota kept relatively stable in a short term after the onset of ACLF. The use of antibiotics only showed moderate impacts on the gut microbiota. The relative abundance of Pasteurellaceae and Model of End Stage Liver Disease score were independent factors predicting mortality rate. Network analysis comparison showed robust correlations between specific bacterial families (Ruminococcaceae and Lachnospiraceae) and inflammatory cytokines (interleukin [IL]-6, tumor necrosis factor alpha, IL-2) in ACLF patients.ConclusionsThese data suggest gut dysbiosis in ACLF and its predictive value for mortality. The results thus open up the possibility of designing diagnostic biomarkers and targeted probiotics aimed at decreasing mortality in ACLF.