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

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 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. DNA methylation is associated with gastric cancer and H. pylori infection related gastritis, while increasing evidence has indicated the substantial involvement of other microbes that reside in the gastric mucosa during gastric tumorigenesis. We investigated the bacterial communities in the non-neoplastic gastric mucosa accompanied with the H. pylori related methylation anomaly. Our findings showed potential correlation between methylation induction and change in bacterial communities characterized as lower bacterial alpha diversity in the gastric mucosa accompanied by H. pylori infection.研究目的：DNA甲基化与胃癌及幽门螺杆菌（Helicobacter pylori，H. pylori）感染密切相关，而日益增多的证据表明，胃黏膜定植的其他微生物在胃肿瘤发生进程中同样发挥关键作用。本研究旨在探究伴随幽门螺杆菌相关甲基化异常的胃黏膜内的细菌群落构成。 材料与方法：从182名无癌患者的胃窦部位采集胃黏膜样本。采用16S rRNA测序技术对细菌群落进行表征分析，并将测序结果与5个基因（IGF2、SLC16A12、SOX11、P2RX7及MYOD1）的幽门螺杆菌相关启动子CpG岛（CpG island，CGI）甲基化水平、LINE1低甲基化程度以及端粒长度进行关联分析。 结果与结论：本研究发现，细菌α多样性越低，CGI甲基化水平越高。多变量分析显示，高龄（t=3.46，p=0.0007）、幽门螺杆菌感染（t=9.99，p=0.02）均与CGI高甲基化显著相关。在菌属或菌科水平上，幽门螺杆菌（Helicobacter）丰度升高与CGI高甲基化呈现最强的相关性；而4种微生物（内孢囊杆菌科（Intrasporangiaceae）、Macellibacteroides、消化链球菌属（Peptostreptococcus）及迪茨氏菌科（Dietziaceae））的丰度降低同样与CGI高甲基化存在关联。本研究结果提示，在伴随幽门螺杆菌感染的胃黏膜中，CGI甲基化的诱导与细菌α多样性降低存在潜在相关性。 DNA甲基化与胃癌及幽门螺杆菌感染相关胃炎密切相关，越来越多的证据表明，胃黏膜定植的其他微生物在胃肿瘤发生过程中发挥着重要作用。本研究旨在探究伴随幽门螺杆菌相关甲基化异常的非肿瘤性胃黏膜内的细菌群落。本研究结果显示，在伴随幽门螺杆菌感染的胃黏膜中，甲基化诱导与以细菌α多样性降低为特征的细菌群落改变存在潜在关联。