Characterization of the Gastric Mucosal Microbiota in Patients with Liver Cirrhosis and Its Associations with Gastrointestinal Symptoms

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 16S ribosomal RNA (rRNA) 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.