Gastric microbiome in gastric cancer sequence depicts diverse microbial structures associated with cancer risk and prognosis

Objective: Increasing evidence indicated substantial involvement of non- Helicobacter pylori microbiota in gastric tumorigenesis. We aimed to elucidate detailed relationship of microbiome dynamics between two different steps in gastric cancer (GC) such as cancer initiation and progression assessed their associations with clinicopathological and molecular changes. Methods: We systemically characterized gastric microbiome during GC development and progression using 944 biopsies from primary GC, non-cancerous gastric mucosa from both GC and non-cancer subjects. The association between specific microbial characteristics and GC risk, prognosis and molecular changes such as TP53 mutation, H. pylori - associated DNA methylation and telomere shortening were also evaluated. Results： Microbial α-diversity in the gastric mucosa was decreased in relation to the GC occurrence, while it increased in primary GC tissue. Such paradoxical change was also observed in specific groups of bacteria during GC occurrence and its progression. GC risk-related microbiome was associated with differentiated GC, severe intestinal metaplasia, H. pylori - associated DNA methylation and telomere shortening, while GC tissue-specific microbiome was associated with more aggressive features of GC and TP53 mutation status. Conclusions： Our findings suggested the different role of non- Helicobacter pylori microbiota in GC initiation and progression steps.