Airway microbiota associated D-phenylalanine promotes non-small cell lung cancer metastasis through epithelial mesenchymal transition
Abstract Background Lung 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 ef...
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2025-06-01
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| Series: | Journal of Translational Medicine |
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| Online Access: | https://doi.org/10.1186/s12967-025-06701-1 |
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| author | Lin Gao Hua Liao Yuehua Chen Cuiping Ye Liping Huang Mingming Xu Jiangzhou Du Jinming Zhang Danhui Huang Shaoxi Cai Hangming Dong |
| author_facet | Lin Gao Hua Liao Yuehua Chen Cuiping Ye Liping Huang Mingming Xu Jiangzhou Du Jinming Zhang Danhui Huang Shaoxi Cai Hangming Dong |
| author_sort | Lin Gao |
| collection | DOAJ |
| description | Abstract Background Lung 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. Methods Bronchoalveolar 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. Results A 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. Conclusion The 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. |
| format | Article |
| id | doaj-art-9abe882f299b4119a8fce0f47f721c70 |
| institution | OA Journals |
| issn | 1479-5876 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj-art-9abe882f299b4119a8fce0f47f721c702025-08-20T02:10:35ZengBMCJournal of Translational Medicine1479-58762025-06-0123111410.1186/s12967-025-06701-1Airway microbiota associated D-phenylalanine promotes non-small cell lung cancer metastasis through epithelial mesenchymal transitionLin Gao0Hua Liao1Yuehua Chen2Cuiping Ye3Liping Huang4Mingming Xu5Jiangzhou Du6Jinming Zhang7Danhui Huang8Shaoxi Cai9Hangming Dong10Chronic Airways Diseases Laboratory, Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical UniversityThe Fifth Affiliated Hospital, Southern Medical UniversityChronic Airways Diseases Laboratory, Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical UniversityDepartment of Critical Care Medicine, Nanfang Hospital, Southern Medical UniversityChronic Airways Diseases Laboratory, Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical UniversityChronic Airways Diseases Laboratory, Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical UniversityChronic Airways Diseases Laboratory, Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical UniversityChronic Airways Diseases Laboratory, Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical UniversityChronic Airways Diseases Laboratory, Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical UniversityChronic Airways Diseases Laboratory, Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical UniversityChronic Airways Diseases Laboratory, Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical UniversityAbstract Background Lung 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. Methods Bronchoalveolar 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. Results A 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. Conclusion The 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.https://doi.org/10.1186/s12967-025-06701-1Non-small cell lung cancer (NSCLC)Airway metabolitesD-phenylalanineTumor metastasisEpithelial mesenchymal transition (EMT) |
| spellingShingle | Lin Gao Hua Liao Yuehua Chen Cuiping Ye Liping Huang Mingming Xu Jiangzhou Du Jinming Zhang Danhui Huang Shaoxi Cai Hangming Dong Airway microbiota associated D-phenylalanine promotes non-small cell lung cancer metastasis through epithelial mesenchymal transition Journal of Translational Medicine Non-small cell lung cancer (NSCLC) Airway metabolites D-phenylalanine Tumor metastasis Epithelial mesenchymal transition (EMT) |
| title | Airway microbiota associated D-phenylalanine promotes non-small cell lung cancer metastasis through epithelial mesenchymal transition |
| title_full | Airway microbiota associated D-phenylalanine promotes non-small cell lung cancer metastasis through epithelial mesenchymal transition |
| title_fullStr | Airway microbiota associated D-phenylalanine promotes non-small cell lung cancer metastasis through epithelial mesenchymal transition |
| title_full_unstemmed | Airway microbiota associated D-phenylalanine promotes non-small cell lung cancer metastasis through epithelial mesenchymal transition |
| title_short | Airway microbiota associated D-phenylalanine promotes non-small cell lung cancer metastasis through epithelial mesenchymal transition |
| title_sort | airway microbiota associated d phenylalanine promotes non small cell lung cancer metastasis through epithelial mesenchymal transition |
| topic | Non-small cell lung cancer (NSCLC) Airway metabolites D-phenylalanine Tumor metastasis Epithelial mesenchymal transition (EMT) |
| url | https://doi.org/10.1186/s12967-025-06701-1 |
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