Abstract
ObjectiveMicrobial infections have been shown to contribute to gastric carcinogenesis, the knowledge of gastric microbiota alteration in this process may provide help in early diagnosis of gastric cancer. The aim of this study was to characterize the microbial changes and identify taxonomic biomarkers across stages of gastric carcinogenesis.MethodsThe gastric microbiota was investigated by 16S rRNA gene analysis in gastric mucosal specimens from 47 patients including superficial gastritis (SG), atrophic gastritis (AG), gastric intraepithelial neoplasia (GIN), and gastric cancer (GC). Differences in microbial composition across the disease stages, especially in GIN and GC were assessed using linear discriminant analysis effect size.ResultsThere was no gradual changing trend in the richness or diversity of the gastric microbiota across stages of gastric carcinogenesis. The relative abundance of dominant taxa at phylum and genus levels didn’t show a gradual shift pattern, and the only four taxa that continuously enriched from SG to GC were Slackia, Selenomonas, Bergeyella, and Capnocytophaga, all of which were oral bacteria. The most representative taxa which were enriched in GC patients were oral bacteria including Parvimonas, Eikenella and Prevotella-2, and environmental bacteria including Kroppenstedtia, Lentibacillus, and Oceanobacillus. The gastric microbiota in GIN patients were characterized by enrichment of intestinal commensals including Romboutsia, Fusicatenibacter, Prevotellaceae-Ga6A1-group, and Intestinimonas. Gastric cardia cancer and non-cardia cancer patients had significantly different microbiota profiles characterized by a higher abundance of Helicobacter in the cardia cancer patients.ConclusionsOur results provide insights on potential taxonomic biomarkers for gastric cancer and precancerous stages, and suggest that gastric microbiota might play different roles in the carcinogenesis of cardia cancer and non-cardia cancer.
Highlights
Gastric cancer remains the second-leading cause of cancer-related deaths worldwide, which emphasizes the need for knowledge of the key changes in the process of carcinogenesis to make early diagnosis
The pathological diagnosis was confirmed for each patient, and the results showed 17 patients of superficial gastritis (SG group), 10 patients of atrophic gastritis with intestinal metaplasia (AG group), five patients of gastric intraepithelial neoplasia (GIN group, including four patients of low-grade GIN and one patient of high-grade GIN), and 15 patients of intestinal-type gastric cancer (GC group), including 27 male patients and 20 female patients in total
We found that the richness of microbiota was significantly higher in AG group than in SG and GC group (Chao1 index, p=0.032 and 0.003, respectively, Figure 1B) and there was no significant difference in microbial diversity among groups (Shannon index, Figure 1C)
Summary
Gastric cancer remains the second-leading cause of cancer-related deaths worldwide, which emphasizes the need for knowledge of the key changes in the process of carcinogenesis to make early diagnosis. Gastric intraepithelial neoplasia, including low-grade and highgrade intraepithelial neoplasia, is the precancerous lesion of gastric cancer, and mainly develops based on atrophic gastritis with intestinal metaplasia. The prognosis of patients with gastric cancer can be greatly improved by early diagnosis and endoscopic resection of GIN. The microbial profile of GIN in the process of gastric carcinogenesis is barely known. We investigate the microbial changes in mucosal biopsies of patients with progressive histological stages along gastric carcinogenesis— from SG, through AG and GIN to GC
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