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 [γ]: 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 (γ = −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.
Highlights
Helicobacter pylori infection is the most substantial risk factor for gastric carcinogenesis[1]
We found that the type IV secretion system (T4SS) protein gene-contributing bacteria including Neisseriaceae and Rhizobiales are abundant in patients with intestinal metaplasia[9]
Through weighted correlation network analysis, we identified two modules associated with an advanced stage of gastric carcinogenesis, namely, the pink and brown modules
Summary
Helicobacter pylori infection is the most substantial risk factor for gastric carcinogenesis[1]. Chronic H. pylori infection induces chronic superficial gastritis, gastric atrophy, and intestinal metaplasia, and may cause the development of gastric cancer[3]. Our group first reported the composition of the gastric microbiome depending on gastric carcinogenesis through 16 S rRNA gene sequencing[5]. We found that the type IV secretion system (T4SS) protein gene-contributing bacteria including Neisseriaceae and Rhizobiales are abundant in patients with intestinal metaplasia[9]. The composition of the gastric microbiome in patients who have precancerous lesions including intestinal metaplasia remains unclear. The advanced stage of gastric carcinogenesis was assessed using the ABCD method, which is an established gastric cancer risk assessment tool based on www.nature.com/scientificreports/. In the ABCD method, groups A, B, C, and D represent low, intermediate, high, and very high risk of gastric cancer, respectively. Several modules consisting of potential bacterial taxa, which correlated with gastric carcinogenesis, were organized
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