Association of <i>Streptococcus anginosus</i> with gastric cancer progression via 2-picolinic acid.

Abstract

e16136 Background: Gastric cancer (GC) is one of the most common cancers and a leading cause of cancer mortality. A diverse community of microorganisms is present in the human stomach and the host-microbe interactions contribute to carcinogenesis and progression of GC. Streptococcus anginosus (SA) was enriched in the gastric mucosa of patients with GC and may promote gastric inflammation, atrophy, and tumorigenesis. However, the potential mechanism is still not fully revealed. Methods: In this work, multi-omics including microbiome, transcriptome, and metabolome data combined with in vivo and in vitro studies were conducted to investigate the potential role and mechanism of SA in process of GC. Results: We analyzed the gastric microbiota of paired tumoral, peritumoral and normal tissues obtained from 144 GC patients by16S rRNA sequencing. SA was enriched stepwise in the normal, peritumoral and tumoral tissues. High level enrichment of SA in tumoral tissue showed poorer prognosis than low level group based on Kaplan-Meier analysis. We isolated and cultured SA from GC tissue, and GC cells co-cultured with SA or treated with SA metabolites enhanced cell proliferation, colony formation, migration and invasion abilities. SA also promoted tumor proliferation in vivo based on mouse transplanted tumor model. Metabolomic analysis showed the elevated level of 2-picolinic acid after treated with SA. We verified the promotional role of 2-picolinic acid on cell proliferation, colony formation and migration in vitro. Conclusions: Thus, this study demonstrated that SA plays significant roles in the progression of GC, and its metabolite, 2-picolinic acid, maybe the key factor in host-microbe interactions.