慢性乙型肝炎患者肠道菌群失调与肝功能改变及血清代谢产

StephenW

Front Microbiol. 2017 Nov 13;8:2222. doi: 10.3389/fmicb.2017.02222. eCollection  2017.
Gut Microbial Dysbiosis Is Associated with Altered Hepatic Functions and Serum Metabolites in Chronic Hepatitis B Patients.Wang J1, Wang Y2, Zhang X1, Liu J1, Zhang Q1, Zhao Y3, Peng J3, Feng Q3, Dai J4, Sun S5,6, Zhao Y1, Zhao L1, Zhang Y2,7, Hu Y3, Zhang M1.
Author information
1State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic and Developmental Sciences, and School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China.2Center for Traditional Chinese Medicine and Systems Biology, Shanghai University of Traditional Chinese Medicine, Shanghai, China.3Institute of Liver Disease, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.4Department of Chemical Biology, College of Chemistry and Molecular Engineering, Peking University, Beijing, China.5School of Pharmacy, Shanghai Jiao Tong University, Shanghai, China.6Unimicro (Shanghai) Technologics Co., Ltd., Shanghai, China.7School of Traditional Dai Medicine, West Yunnan University of Applied Sciences, Jinghong, Yunnan, China.

AbstractChronic hepatitis B (CHB) is a global epidemic disease that results from hepatitis B virus (HBV) infection and may progress to severe liver failure, including liver fibrosis, cirrhosis and hepatocellular carcinoma. Previous evidence has indicated that the dysbiosis of gut microbiota occurs after liver virus infection and is associated with severe liver disease. The aim of this study is to elucidate the compositional and functional characteristics of the gut microbiota in early-stage CHB and to understand their influence on disease progression. We investigated the gut microbial composition of stool samples from 85 CHB patients with low Child-Pugh scores and 22 healthy controls using the Illumina MiSeq sequencing platform. Furthermore, the serum metabolome of 40 subjects was measured by gas chromatography mass spectrometry. Compared with the controls, significant alteration in the gut microbiota was observed in the CHB patients; 5 operational taxonomic units (OTUs) belonging to Actinomyces, Clostridium sensu stricto, unclassified Lachnospiraceae and Megamonas were increased, and 27 belonging to Alistipes, Asaccharobacter, Bacteroides, Butyricimonas, Clostridium IV, Escherichia/Shigella, Parabacteroides, Ruminococcus, unclassified Bacteria, unclassified Clostridiales, Unclassified Coriobacteriaceae, unclassified Enterobacteriaceae, unclassified Lachnospiraceae and unclassified Ruminococcaceae were decreased. The inferred metagenomic information of gut microbiota in CHB showed 21 enriched and 17 depleted KEGG level-2 pathways. Four OTUs, OTU38 (Streptococcus), OTU124 (Veillonella), OTU224 (Streptococcus), and OTU55 (Haemophilus), had high correlations with hosts' hepatic function indices and 10 serum metabolites, including phenylalanine and tyrosine, which are aromatic amino acids that play pathogenic roles in liver disease. In particular, these 4 OTUs were significantly higher in patients with higher Child-Pugh scores, who also showed diminished phenylalanine and tryptophan metabolisms in the inferred gut metagenomic functions. These compositional and functional changes in the gut microbiota in early-stage CHB patients suggest the potential contributions of gut microbiota to the progression of CHB, and thus provide new insight into gut microbiota-targeted interventions to improve the prognosis of this disease.


KEYWORDS: 16S rRNA gene sequencing; aromatic amino acids; chronic hepatitis B; gut sysbiosis; serum metabolomics

PMID:29180991PMCID:PMC5693892DOI:10.3389/fmicb.2017.02222

StephenW

前微生物。 2017年11月13日; 8：2222。 doi：10.3389 / fmicb.2017.02222。 eCollection 2017。
慢性乙型肝炎患者肠道菌群失调与肝功能改变及血清代谢产物相关。
王1 1，王2 2，张曦1，刘1 1，张Q1 1，赵烨3，彭3 3，冯庆3，戴4 4，孙倩5，赵1 1，赵立1，张2 2，胡烨3，张M1。
作者信息

1
    上海交通大学生命科学与生物技术学院代谢与发育科学联合国际研究实验室，微生物代谢国家重点实验室，上海交通大学生命科学与生物技术学院。
2
    上海中医药大学中医系统生物学研究中心，上海
3
    上海中医药大学曙光医院肝病研究所，上海
4
    北京大学化学与分子工程学院化学生物学系，北京。
五
    上海交通大学药学院，上海，中国。
6
    上海联优（上海）科技有限公司，中国上海
7
    云南景洪应用科技大学传统傣医学院，云南景洪。

抽象

慢性乙型肝炎（CHB）是由乙型肝炎病毒（HBV）感染引起的全球性流行性疾病，并可能发展成严重的肝衰竭，包括肝纤维化，肝硬化和肝细胞癌。先前的证据表明肠道微生物群的生态失调发生在肝脏病毒感染后并与严重的肝脏疾病有关。本研究的目的是阐明早期CHB肠道微生物的组成和功能特征，并了解它们对疾病进展的影响。我们使用Illumina MiSeq测序平台研究了来自85名具有低Child-Pugh评分的CHB患者和22名健康对照的粪便样品的肠道微生物组成。此外，通过气相色谱质谱法测量了40位受试者的血清代谢组。与对照组相比，CHB患者肠道菌群显着改变;属于放线菌，梭状梭菌，未分类的纤毛虫科和麦角菌属的5个操作分类单位（OTU）增加，并且属于Alistipes，Asaccharobacter，拟杆菌属，Butyricimonas，Clostridium IV，埃希氏菌/志贺氏菌，Parabacteroides，瘤胃球菌，未分类细菌，未分类梭菌，Unclassified Coriobacteriaceae，未分类的肠杆菌科，未分类的Lachnospiraceae和未分类的Ruminococcaceae下降。推测CHB肠道菌群宏基因组信息显示21个富集的和17个消耗的KEGG二级通路。 4个OTU，OTU38（链球菌），OTU124（韦尼埃利菌），OTU224（链球菌）和OTU55（嗜血菌）与宿主肝功能指数和10个血清代谢物（包括苯丙氨酸和酪氨酸）肝病的致病作用。特别是，Child-Pugh评分较高的患者中，这4种OTUs明显较高，在推断的消化道宏基因组功能中，他们也显示苯丙氨酸和色氨酸代谢减少。早期CHB患者肠道菌群的这些组成和功能变化表明肠道微生物菌群对CHB进展的潜在贡献，从而提供肠道微生物靶向干预以改善该疾病预后的新见解。
关键词：

16S rRNA基因测序;芳香族氨基酸;慢性乙型肝炎;肠道系统生物学血清代谢组学

结论：
    29180991
PMCID：
    PMC5693892
DOI：
    10.3389 / fmicb.2017.02222