<i>Streptococcus anginosus</i>-derived methionine promotes gastric cancer progression.

Abstract

<i>Streptococcus anginosus</i> has been linked with an increasing risk of gastric cancer (GC) and recognised as a signature for GC screening. To investigate the promotional effect of <i>S. anginosus</i> in terms of its metabolic interactions with the host. We used the functional profiles of shotgun metagenomic sequencing from stools to detect bioactive molecules relevant to <i>S. anginosus</i>. In vivo and in vitro experiments were used to validate the facilitation of <i>S. anginosus</i> to GC progression. <i>S. anginosus</i> clinical strains were isolated and cultivated from cancerous tissues to verify its promotion of GC via methionine production. <i>S. anginosus ΔmetE</i> mutant strains were constructed to confirm the critical role of <i>metE</i> in methionine biosynthesis. We verified <i>S. anginosus</i> 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 <i>S. anginosus</i> abundance. Methionine, identified here as one of the primary microbial metabolites derived from <i>S. anginosus,</i> contributed to GC progression in humans and mice. <i>S. anginosus</i> strains from cancerous tissues were found to promote GC via methionine production. We further observed a higher abundance and prevalence of <i>metE</i> gene in cancer stool metagenomes. By constructing an <i>S. anginosus ΔmetE</i> mutant strain, we confirmed the critical role of <i>metE</i> in methionine biosynthesis. Our results elucidate the role of <i>S. anginosus</i>-derived methionine in GC progression, shedding light on intricate metabolic interplay between <i>S. anginosus</i> and host.