Not just H. pylori, this bacteria can also cause stomach cancer and other stomach diseases

Gastric cancer (GC) is the fifth most common cancer in the world and one of the leading causes of cancer deaths. According to the global cancer burden data released by the International Agency for Research on Cancer of the WHO, in 2020, there will be 1,089,000 new cases of gastric cancer and 768,000 deaths worldwide.

H. pylori is a major risk factor for gastric cancer, and it has been classified as a Group 1 carcinogen. H. pylori infection promotes gastritis, gastric atrophy, and intestinal epithelial metaplasia. Only 1–3% of H. pylori infected individuals eventually develop gastric cancer, suggesting that other factors are involved in gastric carcinogenesis.

Several new studies have shown that a large non-H. pylori microbial community exists in the gastric mucosa and that their dysregulation may also play a role in gastric carcinogenesis, which, however, has not been thoroughly studied and explored.

On January 30, 2024, a team from the Chinese University of Hong Kong published a research paper entitled "Streptococcus anginosus promotes gastric inflammation, atrophy, and tumorigenesis in mice" in the journal Cell.

The study identified Streptococcus anginosus as a potential pathogen enriched in gastric cancer through macro-genomic analysis of gastric mucosa samples at different stages of gastric cancer and further demonstrated that Streptococcus anginosus promotes gastric carcinogenesis through direct interaction with the TMPC-ANXA2-MAPK axis of gastric epithelial cells to promote gastric carcinogenesis.

The research team characterized the gastric microbiota of H. pylori-negative patients, ranging from superficial gastritis, atrophic gastritis, and intestinal epithelial metaplasia to gastric cancer, and identified five oral pathogens that are enriched in gastric cancer, including Streptococcus anginosus. This is a Gram-positive, non-spore-producing, non-motile bacterium found primarily in the oral, nasopharyngeal, and gastrointestinal tracts that can cause invasive pyogenic infections.

Streptococcus pharyngitis is highly adapted to acidic conditions (pH = 3–5), which may contribute to its survival in the gastric mucosa, but its role in gastric carcinogenesis and the molecular mechanisms of pathogenesis remain unclear.

This study found that Streptococcus pyogenes rapidly induced acute gastritis, chronic gastritis, gastric mucosal epithelial chemotaxis, and epithelial atypical hyperplasia in both conventional and germ-free mice after long-term infection. Streptococcus pyogenes also accelerated cancer progression in a mouse model of carcinogen-induced gastric cancer and in a mouse model implanted with a gastric cancer cell line. In addition, Streptococcus pyogenes disrupted gastric barrier function, promoted cell proliferation, and inhibited apoptosis.

Mechanistically, the study revealed that TMPC, a surface protein of Streptococcus pyogenes, interacts directly with the gastric epithelial cell receptor Annexin A2 (ANXA2), which mediates the attachment and colonization of Streptococcus pyogenes in the gastric mucosa and consequently the activation of the mitogen-activated protein kinase (MAPK) signaling pathway. Knockdown of ANXA2 was able to deregulate the MAPK-induced activation by Streptococcus pyogenes.

Overall, this study identified Streptococcus pharyngitis as a potential pathogen enriched in gastric cancer through macrogenomic analysis of gastric mucosal samples at different stages of gastric cancer and further demonstrated the causal role of Streptococcus pharyngitis in gastric carcinogenesis.Anxa2

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