Gastric microbiome composition accompanied with the Helicobacter pylori related DNA methylation anomaly.

Abstract

Aim: DNA methylation is associated with gastric cancer and Helicobacter pylori (H. pylori) 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 H. pylori related methylation anomaly.Materials & methods: 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 H. pylori related promoter CpG island (CGI) methylation of five genes (IGF2, SLC16A12, SOX11, P2RX7 and MYOD1), LINE1 hypomethylation and telomere length.Results & conclusion: We showed correlation between lower bacterial alpha diversity and higher CGI methylation. Multivariate analysis demonstrated older age (t = 3.46, p = 0.0007), H. pylori infection (t = 9.99, p < 0.0001) and lower bacterial alfa diversity (Shannon index: t = -2.34, p = 0.02) were significantly associated with CGI hypermethylation. In genus or family levels, increased abundance of Helicobacter was associated with hyper CGI methylation with strongest correlation, while decreased abundance of four bacteria (Intrasporangiaceae family, Macellibacteroides, Peptostreptococcus and Dietziaceae family) 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 H. pylori infection.