Infection with the bacterium Helicobacter pylori is a known risk factor for gastric cancer, and H. pylori is recognized as a carcinogen by the World Health Organization. However, only about 1–3% of people infected with H. pylori develop gastric cancer, which perhaps suggests that other pathogenic bacteria residing in the gastric mucosa could also be causative agents in gastric tumorigenesis. Following this hypothesis, Fu et al. looked for microbial compositional changes in the gastric mucosa of H. pylori-negative patients at various stages of gastric tumorigenesis, from superficial gastritis and atrophic gastritis to intestinal metaplasia and gastric cancer. This led to the identification of Streptococcus anginosus, an oral bacterium, which showed enrichment in the gastric mucosa of patients (of both Asian descent and European descent) with gastric cancer.

The gastric mucosa serves as a barrier against pathogenic microorganisms, and H. pylori is known to perturb barrier function to induce gastric tumorigenesis. Similarly, infection with S. anginosus was shown to compromise barrier integrity, as indicated by loss of the tight junctional protein claudin-18 after infection. Furthermore, the authors were able to demonstrate that the pathogenic effects of S. anginosus were directly attributable to this single bacterium, as germ-free mice inoculated with S. anginosus once a week for 9 months displayed the same phenotypes as the infection model with conventional mice.