Gut Microbial Dysbiosis Is Associated with Altered Hepatic Functions and Serum Metabolites in Chronic Hepatitis B Patients
Gut Microbial Dysbiosis Is Associated with Altered Hepatic Functions and Serum Metabolites in Chronic Hepatitis B Patients
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肠道微生物失调与慢性乙型肝炎患者肝功能和血清代谢物的改变有关
DOI：
10.3389/fmicb.2017.02222
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发表时间：
2017-11-13
影响因子：
5.2
通讯作者：
Zhang, Menghui
中科院分区：
文献类型：
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作者：
Wang, Jing;Wang, Yang;Zhang, Menghui
慢性乙型肝炎(CHB)是由乙型肝炎病毒(HBV)感染引起的一种全球性流行性疾病，可发展为严重的肝功能衰竭，包括肝纤维化、肝硬变和肝细胞癌。以往的证据表明，肠道微生物区系失调发生在肝病毒感染后，并与严重的肝病有关。本研究的目的是阐明慢性乙肝早期肠道微生物区系的组成和功能特征，并了解它们对疾病进展的影响。应用Illumina MiSeq测序平台对85例Child-Pugh评分低的CHB患者和22例健康对照的粪便标本进行肠道微生物成分分析。并用气相色谱-质谱法测定了40例受试者的血清代谢组。与对照组相比，慢性乙肝患者肠道微生物区系发生明显变化，放线菌、限制性感觉梭菌、未分类乳杆菌、巨型单胞菌5个可操作分类单位(OTU)增加，泽泻属、Asaccharbacter、类杆菌、丁立单胞菌、Clostridium IV、Eschericia/Shigella、副杆菌属、瘤胃球菌、未分类菌、未分类梭菌、未分类肠杆菌科、未分类乳杆菌科、未分类肠杆菌科、未分类乳杆菌科、未分类瘤球菌科的27个OTU减少。推测的CHB肠道微生物区系的元基因组信息显示21条KEGG Level-2途径丰富，17条KEGG Level-2途径缺失。OTU38(链球菌)、OTU124(韦氏杆菌)、OTU224(链球菌)和OTU55(嗜血杆菌)与宿主肝功能指标和10种血清代谢物高度相关，其中苯丙氨酸和酪氨酸是引起肝脏疾病的芳香族氨基酸。特别是，在Child-Pugh评分较高的患者中，这4个OTU显著较高，这些患者在推测的肠道亚基因组功能中也显示出苯丙氨酸和色氨酸代谢减弱。这些早期CHB患者肠道微生物区系的组成和功能变化表明肠道微生物区系对CHB的进展有潜在的贡献，从而为肠道微生物区系靶向干预改善该病的预后提供了新的见解。
Chronic 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.