Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou, Taiwan; Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
Biodiversity Research Center, Academia Sinica, Taiwan.
Cell Mol Gastroenterol Hepatol. 2019;8(2):301-318.e2. doi: 10.1016/j.jcmgh.2019.04.008. Epub 2019 Apr 18.
BACKGROUND & AIMS: Gut dysbiosis plays a role in hepatic encephalopathy (HE), while its relationship at the acute episode of overt HE (AHE), the disease progression and clinical outcomes remains unclear. We aimed to identify AHE-specific microbiome and its association to patients' outcomes.
We profiled fecal microbiome changes for a cohort of 62 patients with cirrhosis and AHE i) before treatment, ii) 2-3 days after medication and iii) 2-3 months after recovery, and three control cohorts i) healthy individuals, patients with ii) compensated or iii) decompensated cirrhosis.
Comparison of the microbiome shift from compensated, decompensated cirrhosis, AHE to recovery revealed the AHE-specific gut-dysbiosis. The gut microbiome diversity was decreased during AHE, further reduced after medication, and only partially reversed during the recovery. The relative abundance of Bacteroidetes phylum in the microbiome decreased, whereas that of Firmicute, Proteobacteria and Actinobacteria increased in patients during AHE compared with those with compensated cirrhosis. A total of 70 operational taxonomic units (OTUs) were significantly different between AHE and decompensated cirrhosis abundances. Of them, the abundance of Veillonella parvula increased the most during AHE via a metagenomics recovery of the genomes. Moreover, the relative abundances of three (Alistipes, Bacteroides, Phascolarctobacterium) and five OTUs (Clostridium-XI, Bacteroides, Bacteroides, Lactobacillus, Clostridium-sedis) at AHE were respectively associated with HE recurrence and overall survival during the subsequent one-year follow-up.
AHE-specific gut OTUs were identified that may be involved in HE development and able to predict clinical outcomes, providing new strategies for the prevention and treatment of HE recurrence in patients with cirrhosis.
肠道菌群失调在肝性脑病（HE）中起作用，但其在显性肝性脑病（AHE）急性发作、疾病进展和临床结局中的关系尚不清楚。我们旨在确定 AHE 特异性微生物组及其与患者结局的关系。
我们对 62 例肝硬化伴 AHE 的患者队列进行了粪便微生物组变化的分析：i）治疗前，ii）用药后 2-3 天，iii）恢复后 2-3 个月，以及三个对照队列：i）健康个体，ii）代偿性或 iii）失代偿性肝硬化患者。
比较代偿性、失代偿性肝硬化、AHE 与恢复的微生物组变化，揭示了 AHE 特异性的肠道失调。AHE 期间，肠道微生物组多样性降低，用药后进一步降低，仅在恢复期间部分恢复。与代偿性肝硬化患者相比，AHE 期间微生物组中厚壁菌门的相对丰度降低，而拟杆菌门、变形菌门和放线菌门的相对丰度增加。在 AHE 与失代偿性肝硬化丰度之间共有 70 个操作分类单元（OTUs）存在显著差异。其中，AHE 期间通过宏基因组恢复，普雷沃氏菌属丰度增加最多。此外，在 AHE 期间，有 3 个（拟杆菌属、双歧杆菌属、普雷沃氏菌属）和 5 个 OTUs（梭菌属 XI、拟杆菌属、双歧杆菌属、乳杆菌属、梭菌属 sedis）的相对丰度分别与 HE 复发和随后 1 年随访的总生存相关。
确定了 AHE 特异性肠道 OTUs，它们可能参与 HE 的发生发展，并能够预测临床结局，为肝硬化患者预防和治疗 HE 复发提供了新策略。
