Abstract
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.
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Data availability
All reagents generated in this study and detailed protocols are available from the lead contact upon reasonable request. The 16S rRNA sequencing, bulk RNA-seq, metabolites and single-cell RNA-seq data generated in this study have been deposited in the China National Center for Bioinformation (CNCB) BioProject database under accession numbers PRJCA030100 (mouse data; https://ngdc.cncb.ac.cn/bioproject/browse/PRJCA030100) and PRJCA032988 (human data; https://ngdc.cncb.ac.cn/bioproject/browse/PRJCA032988). Source data are provided with this paper. No new code was generated in this study. The remaining data are available within the Article, Supplementary Information, or Source Data file. Source data are provided with this paper.
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Acknowledgements
We thank members of the Jun Yi and Weiqin Li lab for technical help. We also thank Nanjing university and Jinling Hospital for providing the necessary research infrastructure and resources. This study was supported by Key Project of Jiangsu Provincial Health Commission (K2024054) and Bethune Medical Research Innovation Fund Project (2024-YJ-156-J-036). The results shown here are in part based upon data generated by the TCGA Research Network: https://www.cancer.gov/tcga. We further thank Shanghai Biozeron Biotech Co., Ltd. for assistance with bulk RNA sequencing, Beijing Novogene Biotech Co., Ltd. for support with 16S rRNA sequencing, Guangzhou Verygenome Technology Co., Ltd. and Shanghai Tgene Biotech Co., Ltd. for assisting in mass spectrometry detection, and LC-Bio Technologies (Hangzhou) Co., Ltd. for their help with single-cell sequencing.
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Conceptualization, F.L., J.Y., and Y.H.; methodology, F.L., H.P., Y.H., and L.L.; Investigation, F.L., H.P., Y.H., L.L., S.S., and Q.W.; Formal analysis, F.L. and Y.H.; Resource, W.L. and J.Y.; Data Curation, J.Y., W.L., and F.L.; writing—original draft, F.L.; writing—review and editing, J.Y., F.L., W.L., Y.H., H.P., L.L., S.S., and Q.W.; supervision, J.Y., F.L. and W.L.; funding acquisition, J.Y. and W.L.
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He, Y., Peng, H., Li, L. et al. Valeric acid from oral microbiome suppresses esophageal cancer growth by disrupting eEF1A1 -mediated translational output. Nat Commun (2026). https://doi.org/10.1038/s41467-026-71209-1
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DOI: https://doi.org/10.1038/s41467-026-71209-1
