Gut Dysbiosis Associated With Hepatitis C Virus Infection
Gut Dysbiosis Associated With Hepatitis C Virus Infection
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DOI：
10.1093/cid/ciy205
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发表时间：
2018-09-15
影响因子：
11.8
通讯作者：
Tanaka, Yasuhito
中科院分区：
文献类型：
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作者：
Inoue, Takako;Nakayama, Jiro;Tanaka, Yasuhito
背景。关于丙型肝炎病毒（HCV）感染对肠道菌群的影响以及肠道菌群改变与慢性丙型肝炎（CHC）进展之间的关系知之甚少。我们对CHC患者和健康人的肠道菌群组成进行了比较研究。将166例CHC患者的粪便样本与23例健康人的粪便样本进行比较；采用16S核糖体RNA基因测序分析肠道菌群。CHC患者诊断为血清丙氨酸转氨酶持续正常，无肝硬化（PNALT, n = 18）、慢性肝炎（CH, n = 84）、LC （n = 40）和LC中的肝细胞癌（n = 24）。与健康人群相比，HCV感染者的细菌多样性较低，梭菌目减少，链球菌和乳酸杆菌增加。微生物群失调在PNALT阶段已经出现，拟杆菌科和肠杆菌科菌群短暂增加。微生物群落宏基因组学预测显示，CHC进展过程中，主要由绿绿链球菌编码的脲酶基因增加，这与CHC和LC患者的粪便pH值明显高于健康个体或PNALT阶段的粪便pH值一致。丙型肝炎病毒感染与肠道生态失调有关，即使在患有轻度肝病的患者中也是如此。此外，翠绿链球菌的过度生长可以解释CH和LC的高氨血症。进一步的研究将有助于提出一种新的治疗策略，因为肠道微生物组可以通过治疗改变，潜在地减少慢性肝病的并发症。
Background. Little is known about the effect of hepatitis C virus (HCV) infection on gut microbiota and the relationship between alteration of gut microbiota and chronic hepatitis C (CHC) progression. We performed a comparative study of gut microbiota composition between CHC patients and healthy individuals.Methods. Fecal samples from 166 CHC patients were compared with those from 23 healthy individuals; the gut microbiota community was analyzed using 16S ribosomal RNA gene sequencing. CHC patients were diagnosed with persistently normal serum alanine aminotransferase without evidence of liver cirrhosis (LC) (PNALT, n = 18), chronic hepatitis (CH, n = 84), LC (n = 40), and hepatocellular carcinoma in LC (n = 24).Results. Compared with healthy individuals, bacterial diversity was lower in persons with HCV infection, with a decrease in the order Clostridiales and an increase in Streptococcus and Lactobacillus. Microbiota dysbiosis already appeared in the PNALT stage with the transient increase in Bacteroides and Enterobacteriaceae. Predicted metagenomics of microbial communities showed an increase in the urease gene mainly encoded by viridans streptococci during CHC progression, consistent with a significantly higher fecal pH in CH and LC patients than in healthy individuals or those in the PNALT stage.Conclusions. HCV infection is associated with gut dysbiosis, even in patients with mild liver disease. Additionally, overgrowth of viridans streptococci can account for hyperammonemia in CH and LC. Further studies would help to propose a novel treatment strategy because the gut microbiome can be therapeutically altered, potentially reducing the complications of chronic liver disease.