Metaplasia Enables Stomach Colonization by Fusobacterium animalis

Area of Science:

• Microbiology
• Gastroenterology
• Oncology

Background:

• Helicobacter pylori infection is a primary risk factor for gastric cancer globally.
• H. pylori disrupts the gastric microbiome, allowing secondary colonization by oral bacteria like Fusobacterium species, which are linked to gastrointestinal cancers.

Purpose of the Study:

• To investigate the role of Fusobacterium species, specifically F. animalis and F. nucleatum, in the context of H. pylori-associated gastric changes and cancer.
• To understand the mechanisms of adherence, invasion, and colonization of these bacteria in the gastric environment.

Main Methods:

• In vitro studies using cultured human gastric adenocarcinoma cells to assess bacterial adherence and invasion.
• In vivo studies using a mouse model of gastric metaplasia to evaluate bacterial colonization.
• Analysis of bacterial interactions with host cell glycoproteins (GalNAc) and environmental factors (hypoxia, gastric acidity).

Main Results:

• Both F. animalis and F. nucleatum invaded gastric adenocarcinoma cells, with F. animalis showing higher adherence and invasion rates.
• Exogenous GalNAc inhibited bacterial adherence and invasion, highlighting the role of the Fap2 adhesin.
• In a mouse model, F. animalis colonized metaplastic gastric tissue, forming biofilms, while F. nucleatum did not colonize.
• Gastric metaplasia upregulated Gal-GalNAc and reduced gastric acidity, promoting F. animalis colonization, independent of H. pylori presence or inflammation.

Conclusions:

• H. pylori-induced gastric metaplasia creates a niche for secondary colonization by F. animalis.
• This interaction suggests a pathway where H. pylori infection predisposes the stomach to colonization by another cancer-associated microbe, F. animalis.