Chen Yanfei, Guo Jing, Qian Guirong, Fang Daiqiong, Shi Ding, Guo Lihua, Li Lanjuan
State Key Laboratory for Diagnosis and Treatment of Infectious Disease, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou, China.
J Gastroenterol Hepatol. 2015 Sep;30(9):1429-37. doi: 10.1111/jgh.12932.
Bacterial 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.
This research characterized the fecal microbiota in patients with ACLF and analyzed the temporal stability of gut microbiota during illness.
Fecal 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.
There 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.
These 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.
肠道细菌易位在慢加急性肝衰竭（ACLF）的病理生理学中起重要作用。然而，先前研究中对ACLF患者肠道菌群失调的记录并不广泛。
本研究对ACLF患者的粪便微生物群进行特征分析，并分析患病期间肠道微生物群的时间稳定性。
采用16S核糖体DNA焦磷酸测序法分析79例ACLF患者（其中42例患者在首次就诊后的接下来4周内进行随访以进行纵向研究）和50例健康对照者的粪便微生物群。
ACLF组与对照组之间存在显著差异。ACLF患者的总体微生物多样性和丰富度显著低于对照组。ACLF患者中拟杆菌科、瘤胃球菌科和毛螺菌科的丰度较低，但巴斯德菌科、链球菌科和肠球菌科的丰度较高。肝性脑病ACLF患者中毛螺菌科的相对丰度明显降低。ACLF发病后短期内肠道微生物群保持相对稳定。使用抗生素对肠道微生物群仅显示出中度影响。巴斯德菌科的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，ACLF患者中特定细菌家族（瘤胃球菌科和毛螺菌科）与炎性细胞因子（白细胞介素[IL]-6、肿瘤坏死因子α、IL-2）之间存在强相关性。
这些数据提示ACLF患者存在肠道菌群失调及其对死亡率的预测价值。因此，这些结果为设计诊断生物标志物和靶向益生菌以降低ACLF患者死亡率开辟了可能性。
