Gastric cancer-associated bacteria exhibit distinct butyrate and pyruvate metabolism: a metabolomic analysis of F. nucleatum, N. subflava, and H. pylori

BACKGROUND: Butyrate and pyruvate are central metabolites in anaerobic microbial metabolism, with key roles in gastrointestinal physiology. We recently identified Fusobacterium nucleatum (F. nucleatum) and Neisseria subflava (N. subflava) as non-Helicobacter pylori (H. pylori) bacteria potentially involved in gastric cancer development. However, the metabolic pathways distinguishing F. nucleatum, N. subflava, and H. pylori remain poorly characterized. METHODS: We performed capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS) to profile the metabolic outputs of these three species under isolated culture conditions. RESULTS: Distinct metabolic signatures were observed: F. nucleatum predominantly synthesized butyrate via the acetyl-CoA pathway, whereas N. subflava produced high levels of pyruvate and employed a cyclical route regenerating pyruvate from acetyl-CoA. In contrast, H. pylori lacked significant production of either metabolite. CONCLUSIONS: This study delineates species-specific metabolic programs among gastric cancer-associated bacteria and highlights unique butyrate and pyruvate metabolism as a potential axis of microbe-host and microbe-microbe interaction in the gastric environment.