Streptococcus anginosus-derived methionine promotes gastric cancer progression.

BACKGROUND

Streptococcus anginosus has been linked with an increasing risk of gastric cancer (GC) and recognised as a signature for GC screening.

OBJECTIVE

To investigate the promotional effect of S. anginosus in terms of its metabolic interactions with the host.

DESIGN

We used the functional profiles of shotgun metagenomic sequencing from stools to detect bioactive molecules relevant to S. anginosus. In vivo and in vitro experiments were used to validate the facilitation of S. anginosus to GC progression. S. anginosus clinical strains were isolated and cultivated from cancerous tissues to verify its promotion of GC via methionine production. S. anginosus ΔmetE mutant strains were constructed to confirm the critical role of metE in methionine biosynthesis.

RESULTS

We verified S. anginosus facilitated GC progression in vivo and in vitro. Our functional analysis of metagenomes revealed a significant enrichment of bacterial methionine biosynthesis pathways in GC patients with high S. anginosus abundance. Methionine, identified here as one of the primary microbial metabolites derived from S. anginosus, contributed to GC progression in humans and mice. S. anginosus strains from cancerous tissues were found to promote GC via methionine production. We further observed a higher abundance and prevalence of metE gene in cancer stool metagenomes. By constructing an S. anginosus ΔmetE mutant strain, we confirmed the critical role of metE in methionine biosynthesis.

CONCLUSION

Our results elucidate the role of S. anginosus-derived methionine in GC progression, shedding light on intricate metabolic interplay between S. anginosus and host.