Non-Helicobacter pylori Gastric Microbiome Modulates Prooncogenic Responses and Is Associated With Gastric Cancer...

Area of Science:

• Microbiology
• Oncology
• Gastroenterology

Background:

• Helicobacter pylori is a primary bacterial carcinogen for gastric cancer (GC).
• Gastric cancer can still develop post-H. pylori eradication.
• The role of specific gastric microbiome constituents in GC pathogenesis remains unclear.

Purpose of the Study:

• To investigate the association between gastric microbiome composition and GC risk.
• To elucidate the pathogenic role of specific bacteria in GC development after H. pylori eradication.

Main Methods:

• 16S rRNA sequencing of human gastric mucosal samples.
• Coculturing bacteria with gastric epithelial cells and inoculation into mice.
• Analysis of transcriptomic changes, DNA damage, and inflammation.
• Examination of bacterial reads in GC tissues and cancer genome atlas data.

Main Results:

• A dysbiotic subgroup enriched with Fusobacterium and Neisseria species showed a higher GC incidence post-H. pylori eradication.
• These bacteria activated prooncogenic pathways, induced inflammation, and exhibited genotoxic metabolites.
• Bacterial presence correlated with an inflammatory signature and increased tumor mutation burden.

Conclusions:

• Dysbiotic gastric microbiota contributes to GC development after H. pylori eradication.
• Specific bacteria like Fusobacterium and Neisseria play a pathogenic role via direct host-bacteria interactions.