Valeric acid from oral microbiome suppresses esophageal cancer growth by disrupting eEF1A1 -mediated translational output

Dysbiosis of the oral microbiome has been associated with esophageal squamous cell carcinoma (ESCC), but how it impacts ESCC remains largely unknown. Surprisingly, we find that the oral microbiota derived from ESCC patients-not that from healthy controls-exhibits potent inhibitory and cytotoxic effects on ESCC cells. This anti-tumor effect is attributable to Veillonella, which is enriched in the ESCC-associated microbiota. Mechanistically, Veillonella produces valeric acid, which is transported into cells via MCT1 and inhibits the GTPase activity of eEF1A1, thereby suppressing protein translation. These findings identify valeric acid as a potential postbiotic for ESCC treatment and underscore the necessity of functional validation beyond observational and correlative studies.