【摘要】 研究表明,肝硬化患者的口腔和肠道微生物群与健康人群存在差异。胃位于口腔和肠道之间,关于其黏膜微生物群结构所知甚少。本研究采用16S r RNA焦磷酸测序技术分析了肝硬化患者和对照组的胃黏膜微生物群。研究发现,组织学和测序法均证实肝硬化患者幽门螺杆菌感染率显著降低。在幽门螺杆菌阴性人群中,可以按细菌组成结构将胃黏膜微生物群分为4个聚类,其中聚类1和2主要是肝硬化患者,聚类3主要是健康人群,而聚类4中肝硬化患者和健康人群各占一半左右。这些不同聚类间的成分和功能存在显著差异。在属的水平上,聚类1和2分别富集奈瑟菌和链球菌。在功能基因分类上,相对而言,聚类2缺乏涉及遗传信息处理以及与聚糖生物合成和代谢相关的功能基因。胃黏膜菌群结构表现为聚类2的患者胃肠道症状更严重,既往内镜下曲张静脉的治疗率显著高于其他组。我们的研究结果表明,在肝硬化中,幽门螺杆菌和非幽门螺杆菌的定植都受到影响。虽然幽门螺杆菌阴性的胃黏膜微生物结构表现出相当大的异质性,但特定的胃微生物群与临床特征之间仍然存在相关性。既往内镜下静脉曲张治疗会引起胃黏膜菌群结构明显改变,从而加重幽门螺杆菌阴性肝硬化患者的胃肠道症状。更多还原

【Abstract】 Several studies have indicated that the oral and gut microbiota may exhibit differences in patients with cirrhosis. Less is known about the microbiota in the stomach, which is located between the oral cavity and the intestinal tract. In this study, the gastric mucosal microbiota of patients with liver cirrhosis and controls were analyzed with 16 S ribosomal RNA(r RNA) pyrosequencing. Cirrhotic patients had significantly lower Helicobacter pylori(H. pylori) infection rates, as confirmed by both the histological method and the pyrosequencing method. In H. pylori-negative subjects, gastric bacterial communities of healthy and cirrhosis cohorts were clustered into four clusters based on bacterial compositions:Cluster＿1 and Cluster＿2(mostly cirrhosis), Cluster＿3(mostly healthy), and Cluster＿4(around half of each). Compositional and functional differences were observed among these different clusters. At the genus level, Cluster＿1 and Cluster＿2 showed enrichment of Neisseria and Streptococcus, respectively.Functionally, Cluster＿2 was characterized as depleted of genetic information processing, as well as of modules related to glycan biosynthesis and metabolism. Patients in Cluster＿2 had more severe gastrointestinal symptoms and a higher rate of previous endoscopic variceal ligation(EVL) therapy than patients in other clusters. Our findings suggest that the colonization of both H. pylori and non-H. pylori is influenced in liver cirrhosis. Although the H. pylori-negative gastric mucosal microbiota showed considerable heterogeneity, associations between specific gastric microbiota and clinical characteristics could be observed. Previous EVL therapy might lead to a distinct structure of the gastric mucosal microbiota, thus aggravating the gastrointestinal symptoms in H. pylori-negative cirrhotic patients.更多还原