Network construction of gastric microbiome and organization of microbial modules associated with gastric carcinogenesis

Abstract

In addition to Helicobacter pylori infection, nitrosating/nitrate-reducing bacteria and type IV secretion system (T4SS) protein gene-contributing bacteria have been proposed as potential causes of gastric cancer development. However, bacterial modules related with gastric carcinogenesis have not been clarified. In this study, we analyzed gastric microbiome using the gastric mucosal samples obtained from the Hanyang University Gastric Microbiome Cohort by 16S rRNA gene sequencing. Weighted correlation network analysis was performed to construct a microbiome network and to identify microbial modules associated with gastric carcinogenesis. At the family level, 420 bacterial taxa were identified in the gastric microbiome of 83 participants. Through network analysis, 18 microbial modules were organized. Among them, two modules-pink and brown-were positively correlated with a higher-risk of gastric cancer development such as intestinal metaplasia with no current H. pylori infection (correlation coefficient [gamma]: pink module, 0.31 [P= 0.004], brown module, 0.26 [P= 0.02]). At the family level, twenty-two and thirty-two bacterial taxa belonged to the pink and brown modules, respectively. They included nitrosating/nitrate-reducing bacteria, T4SS protein gene-contributing bacteria, and various other bacteria, including Gordoniaceae, Tsukamurellaceae, Prevotellaceae, Cellulomonadaceae, Methylococcaceae, and Procabacteriaceae. The blue module, which included H. pylori, was correlated negatively with intestinal metaplasia (gamma = -0.49 [P ˂ 0.001]). In conclusion, intragastric bacterial taxa associated with gastric carcinogenesis can be classified by network analysis. Microbial modules may provide an integrative view of the microbial ecology relevant to precancerous lesions in the stomach.