BackgroundLung　cancer　is　the　leading　cause　of　cancer-related　death　worldwide,　and　patients　with　distant　metastasis　have　a　poor　prognosis.　Various　studies　have　reported　that　microbiota　and　metabolites　significantly　differ　between　healthy　individuals　and　lung　cancer　patients.　However,　the　effects　of　metabolites　on　tumor　formation　and　metastasis　are　unclear.　Therefore,　our　study　aimed　to　determine　the　correlation　between　airway　metabolites　and　microbiota,　along　with　their　respective　roles　in　lung　cancer　metastasis.MethodsBronchoalveolar　lavage　fluid　(BALF)　samples　were　collected　from　30　non-small　cell　lung　cancer　(NSCLC)　patients,　including　11　patients　without　metastasis　(M0)　and　19　patients　with　metastasis　(M1).　Integrated　pathogenic　metagenomic　and　Liquid　chromatography-mass　spectrometry　(LC-MS)　analyses　were　employed　to　explore　differences　between　two　groups.　The　omics　data　were　analyzed　and　integrated　via　Spearman＇s　correlation　coefficient.　Specific　metabolites　were　subsequently　used　to　intervene　in　lung　cancer　cells　and　animal　models　to　assess　their　influence　on　tumor　metastasis.ResultsA　total　of　801　metabolites　were　identified　in　the　BALF　of　all　patients.　Compared　with　those　in　the　M0　group,　48　metabolites　in　the　M1　group　were　significantly　different.　D-phenylalanine　was　notably　upregulated　in　M1　and　was　positively　related　to　Metamycoplasma　salivarium.　Intranasal　administration　of　D-phenylalanine　promoted　tumor　intrapulmonary　metastasis　and　induced　epithelial　mesenchymal　transition　(EMT)　process　in　NSCLC　mouse　models.　Moreover,　D-phenylalanine　promotes　the　proliferation　of　non-small　cell　lung　cancer　cells　and　facilitates　their　migration　and　invasion　via　EMT.ConclusionThe　airway　microbiota　associated　D-phenylalanine　could　promote　lung　cancer　metastasis　via　EMT,　which　could　be　a　new　predictor　for　the　diagnosis　of　tumor　metastasis　in　NSCLC　patients.