Gastric microbiome composition accompanied with the <i>Helicobacter pylori</i> related DNA methylation anomaly

<b>Aim:</b> DNA methylation is associated with gastric cancer and <i>Helicobacter pylori</i> (<i>H. pylori</i>) infection, while increasing evidence indicated involvement of other microbes reside in gastric mucosa during gastric tumorigenesis. We investigated bacterial communities in the gastric mucosa accompanied with <i>H. pylori</i> related methylation anomaly.<b>Materials & methods:</b> Gastric mucosa samples from antrum were obtained from 182 cancer-free patients. Bacterial communities were evaluated using 16S rRNA sequencing. The result was correlated with <i>H. pylori</i> related promoter CpG island (CGI) methylation of five genes (<i>IGF2, SLC16A12, SOX11, P2RX7 and MYOD1</i>), LINE1 hypomethylation and telomere length.<b>Results & conclusion:</b> We showed correlation between lower bacterial alpha diversity and higher CGI methylation. Multivariate analysis demonstrated older age (t = 3.46, <i>p</i> = 0.0007), <i>H. pylori</i> infection (t = 9.99, <i>p</i> < 0.0001) and lower bacterial alfa diversity (Shannon index: t = -2.34, <i>p</i> = 0.02) were significantly associated with CGI hypermethylation. In genus or family levels, increased abundance of <i>Helicobacter</i> was associated with hyper CGI methylation with strongest correlation, while decreased abundance of four bacteria (<i>Intrasporangiaceae family, Macellibacteroides</i>, <i>Peptostreptococcus</i> and <i>Dietziaceae family</i>) was also associated with hyper CGI methylation. Our findings suggest the potential correlation between CGI methylation induction and lower bacterial alpha diversity in the gastric mucosa accompanied by <i>H. pylori</i> infection.