Large-Scale Survey of Gut Microbiota Associated With MHE Via 16S rRNA-Based Pyrosequencing
Large-Scale Survey of Gut Microbiota Associated With MHE Via 16S rRNA-Based Pyrosequencing
复制标题
通过基于 16S rRNA 的焦磷酸测序对与 MHE 相关的肠道微生物群进行大规模调查
DOI：
10.1038/ajg.2013.221
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发表时间：
2013-10-01
影响因子：
9.8
通讯作者：
Shi, Peng
中科院分区：
文献类型：
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作者：
Zhang, Zhigang;Zhai, Huiqin;Shi, Peng
目的：阐明最小肝性脑病（MHE）相关肠道微生物组可能有助于预测和降低肝硬化患者MHE的高风险。方法：从没有明显肝性脑病的肝硬化患者中招募和筛选26例MHE患者，这些患者通过两种测试方式（数字连接测试A部分和数字符号测试）的异常来定义。以26例MHE匹配的正常亲属和25例无MHE的肝硬化患者为对照，采用16S核糖体RNA （rRNA）法对77例受试者粪便中的241622条细菌16S rDNA基因序列进行检测和分析。结果：通过多次比较分析，我们的研究结果发现，与正常人相比，在合并和不合并MHE的肝硬化患者中，链球菌科（Streptococcaceae）和韦氏菌科（Veillonellaceae）这两个细菌家族的持续过度代表。此外，我们还发现了mhe独特的肠道微生物群相互作用模式，这在很大程度上受这两个家族成员的影响。根据这些发现，我们进一步发现，肠道含脲酶细菌唾液链球菌在正常组中不存在，但在有和没有MHE的肝硬化患者中存在。肝硬化MHE患者的唾液链球菌丰度显著高于无MHE患者（P= 0.030），且该细菌数量的变化与肝硬化MHE患者氨积累呈正相关（R= 0.58， P= 0.003），无MHE患者无此相关性。结论：肝硬化患者肠道菌群失调可能与MHE的存在有关，特别是与MHE中氨增高表型有关。肠道增氨细菌唾液链球菌有望成为肝硬化MHE患者降氨治疗的潜在生物标志物。
OBJECTIVES: Elucidating the minimal hepatic encephalopathy (MHE)-associated gut microbiome may help in predicting and lowering the high risk for MHE in patients with cirrhosis.METHODS: Twenty-six MHE patients were recruited and screened from among those with liver cirrhosis without overt hepatic encephalopathy as defined by abnormality seen on two test modalities: number connection test part A and the digit symbol test. Using 26 MHE-matched normal relatives and 25 cirrhotic patients without MHE as controls, by means of 16S ribosomal RNA (rRNA)-based pyrosequencing, we examined and analyzed 241,622 bacterial 16S rDNA gene sequences from feces of 77 subjects.RESULTS: Using multiple comparative analyses, our results found the continuous overrepresentation of two bacterial families, Streptococcaceae and Veillonellaceae, in cirrhotic patients with and without MHE, compared with normal individuals. In addition, we also discovered an MHE-unique interplay pattern of gut microbiota largely influenced by the members of those two families. Following these findings, we further revealed that gut urease-containing bacteria Streptococcus salivarius was absent in the normal group but was present in cirrhotic patients with and without MHE. The abundance of S. salivarius was significantly higher in cirrhotic patients with MHE than in those without (P= 0.030), and the change in the amount of this bacteria was positively correlated with ammonia accumulation (R= 0.58, P= 0.003) in cirrhotic patients with MHE but not in those without.CONCLUSIONS: Gut microbiota dysbiosis may be associated with the presence of MHE in cirrhotic patients, in particular with ammonia-increasing phenotype in MHE. Gut ammonia-increasing bacteria S. salivarius might be expected to be a potential biomarker of ammonia-lowering therapies in cirrhotic patients with MHE.