New Mechanism in Gastric Cancer Development

A study published in the journal Gut—led by academic Fang Jingyu from the Chinese Academy of Sciences (CAS) and his team at Renji Hospital, Shanghai Jiao Tong University School of Medicine in collaboration with BGI Genomics—described the molecular mechanism by which methionine metabolites produced by Streptococcus anginosus (Sa) can promote the development of gastric cancer. Gastric cancer is the fifth most commonly diagnosed type of cancer worldwide, with high incidence in regions such as East Asia (China, Japan, Korea) and Eastern Europe. Traditionally, Helicobacter pylori has been recognized as the main bacterial agent associated with this cancer, classified as a Group 1 carcinogen by the World Health Organization (WHO). However, in this scenario, a new element emerges: the bacterium Streptococcus anginosus (Sa), traditionally identified as a member of the human microbiome, is now implicated in the promotion of stomach cancer through specific metabolic mechanisms. Metagenomic analysis revealed a positive correlation between the abundance of Sa's methionine biosynthesis pathway, as well as increased levels of associated metabolites in tumor tissues. A key challenge in this field of research is the high microbial diversity and variability of strains present in the gastric microbiome. By comparatively analyzing the genomes of these strains, the presence of the metE gene, essential for methionine biosynthesis, was identified, reinforcing the link between microbial metabolic functions and tumor progression. To address this complexity, researchers successfully isolated and cultivated three strains of Sa directly from clinical gastric tumors, demonstrating their methionine synthesis capacity and their tumor-promoting effects in both mouse models and gastric cancer cell lines. The study showed that methionine produced by Sa increases the expression of the enzyme MAT2A and facilitates the intracellular transport of this metabolite, providing energy and substrates that favor tumor proliferation. This finding deepens the understanding of the relationship between the microbiota and gastric carcinogenesis, and opens new avenues for the design of prevention strategies and targeted therapies. In addition to consolidating the role of Sa as a possible risk biomarker for gastric cancer, these discoveries have critical implications for prevention and clinical management. However, the stomach harbors a more diverse microbial community, and recent studies have identified Sa as an enriched component in the microbiota of gastric cancer patients, suggesting a broader role for internal microbes in oncogenesis. The accumulated evidence establishes a paradigm in which bacterial metabolites are central pieces in the etiology of gastric cancer and potential targets for preventive and therapeutic precision interventions. This advance opens new research lines that could transform the way gastric cancer risk and treatment are conceived, emphasizing a perspective that integrates the role of internal microbes in cancer biology and global public health.