The Faculty of Medicine (CU Medicine) of the Chinese University of Hong Kong (CUHK) announced on March 13 its latest research findings that a bacterium called Streptococcus anginosus (S. anginosus) can be a pathogen that promotes gastric tumor formation. The research results have been published in Cell, the top international journal in biology. The research team plans to study, in its next phase, how to inhibit S. anginosus to reduce the risk of gastritis and gastric cancer.
According to CU Medicine of CUHK, gastric cancer is the fifth most common cancer in the world and the sixth most common cancer in Hong Kong. Although Helicobacter pylori (H. pylori) infection is known to be a major risk factor for gastric cancer, only 1 percent to 3 percent of those infected will eventually develop it. So, whether any other microorganisms apart from H. pylori could be involved, there is still not a definite answer from the medical community.
It was from this perspective that the CUHK research team started exploring the likelihood of other factors. They first looked at the non-H. pylori microbiome in patients at different stages of gastric tumorigenesis, from superficial gastritis, atrophic gastritis, and intestinal metaplasia to cancer, and discovered that five oral pathogens, which included S. anginosus were enriched in the patients’ gastric mucosa. S. anginosus exists mainly in the oral cavity, nasopharynx, gastrointestinal tract, as well as the vaginal tract, and can enter all sterile parts of the body and cause invasive infections.
Because S. anginosus can adapt to a fairly acidic environment of pH 3 to 5, it can survive and colonize in the gastric mucosa. The team’s laboratory data shows that S. anginosus infection is very common and can be detected in the gastric mucosa of 50 to 70 percent of the Chinese subjects, compared to the prevalence of H. pylori, which is about 40 percent.
The research team then used a mice model to study how S. anginosus induces inflammation and causes gastric cancer. They found that mice developed acute gastritis soon after being infected with S. anginosus. They then developed into chronic gastritis, which then developed gastric mucinous metaplasia, and dysplasia over an extended period.
The team then explored the related carcinogenesis mechanism and found that the surface protein TMPC of S. anginosus directly interacted with the epithelial cell receptor ANXA2 in the stomach, allowing S. anginosus to colonize the gastric mucosa and initiate MAPK signaling to promote gastric cancer progression.
Professor Yu Jun, Director of the Institute of Digestive Diseases at CUHK, pointed out that the team spent more than five years completing the research and establishing the carcinogenic process and mechanism of S. anginosus. The next phase will be to study the therapeutic potential of targeting this microbiome to reduce the risk of gastric inflammation and gastric cancer.
Professor Joseph Sung Jao-yiu, Emeritus Chair Professor of the Department of Internal Medicine and Therapeutics of CU Medicine at CUHK, said that the commonly recognized risk factors for gastric cancer are H. pylori infection and family inheritance. This study found that the enrichment of S. anginosus in the gastric mucosa of patients across different stages of gastric cancer opens up a whole new direction for understanding the pathogenesis of gastric cancer. Co-infection with S. anginosus and H. pylori would lead to an even higher risk of developing precancerous atrophy, metaplasia, or gastric cancer.
