promotes gastric cancer metastasis via NA-mediated NAD metabolism reprogramming and glycolytic activation.

[BACKGROUND] Gastric cancer (GC) is one of the most common malignancies worldwide and it is the third leading cause of cancer-related death in China. While is a known GC pathogen, its abundance declines in tumours and the role of other bacteria in GC metastasis remains unclear.

[OBJECTIVE] We aim to investigate the mechanisms of other bacteria influencing GC progression and metastasis.

[DESIGN] Integrated intratumoural microbiome-metabolome analysis identified GC-associated microbes and metabolites. We then demonstrated the pro-metastatic role of (, Ab) and its metabolite nicotinic acid (NA) using genetic, molecular and in vivo approaches.

[RESULTS] The abundance of was significantly increased in GC tissues, correlating with advanced tumour stage and intratumoural NA levels. Fluorescence in situ hybridisation confirmed its colonisation in GC tumours. In co-culture systems, increased NA levels, enhancing nicotinamide adenine dinucleotide (NAD) metabolism and increasing 1-Methylnicotinamide accumulation in tumour cells. Mutagenesis of the bacterial NA synthase gene confirmed that excreted an NA-dependent pro-metastasis effect. Mechanically, promotes GC metastasis by reprogramming tumour cell glucose metabolism, reducing oxidative phosphorylation while enhancing glycolysis and activating the hypoxia-inducible factor-1 pathway in GC cells through metabolites both in vivo and in vitro.

[CONCLUSIONS] This study elucidates the role of in enhancing NAD metabolism in GC cells through NA synthesis, consequently promoting GC metastasis. These findings establish a microbiota-metabolism axis as a mechanistic foundation for developing targeted therapeutic strategies against GC metastasis.