Airway microbiota associated D-phenylalanine promotes cancer metastasis through epithelial mesenchymal transition in non-small cell lung cancer

<bold>Background:</bold> Lung cancer (LC) is the leading cause of cancer-related mortality worldwide. Despite various studies reporting the lung microbiome in LC, the relationship between microbiome and cancer metastasis remains poorly understood. <bold>Methods:</bold> Bronchoalveolar lavage fluid (BALF) samples were collected from 30 NSCLC patients, including 11 patients without metastasis (M0) and 19 patients with metastasis (M1). Subsequently, we combined metagenomics and liquid chromatography-mass spectrometry (LC-MS) techniques to investigate the microbiota composition and metabolic profile of the BALF samples. <bold>Results:</bold> There were a total of 801 metabolites identified. In comparison to M0 patients, 48 metabolites were significantly altered. Analysis of metabolome revealed differences in several amino acids and their derivatives. D-phenylalanine exhibited the highest fold change among the 48 metabolites. Additionally, the association analysis of microbiome and metabolome data revealed a significant correlation between D-phenylalanine and Metamycoplasma salivarium. In vivo, intranasal administration of D-phenylalanine enhanced lung cancer metastasis in mice, while in vitro it promoted NSCLC cell proliferation, migration, and invasion, and facilitated epithelial-mesenchymal transition (EMT). <bold>Conclusions:</bold> In summary, our research described the characteristics and differences in the airway microbiome and metabolome. D-phenylalanine has been proven to promote cancer metastasis through EMT in NSCLC, suggesting its potential as a therapeutic target for LC. <fig><object-id>erj;64/suppl_68/OA1091/F1</object-id><object-id>F1</object-id><object-id>F1</object-id><graphic></graphic></fig> <fig><object-id>erj;64/suppl_68/OA1091/F2</object-id><object-id>F2</object-id><object-id>F2</object-id><graphic></graphic></fig>