Abstract
BACKGROUND: Lung cancer is the leading malignant disease and cause of cancer-related death worldwide. Most patients with lung cancer had insignificant early symptoms so that most of them were diagnosed at an advanced stage. In addition to factors such as smoking, pollution, lung microbiome and its metabolites play vital roles in the development of lung cancer. However, the interaction between lung microbiota and carcinogenesis is lack of systematically characterized and controversial. Therefore, the purpose of this study was to excavate the features of the lung microbiota and metabolites in patients and verify potential biomarkers for lung cancer diagnosis. METHODS: Lung tissue flushing solutions and bronchoalveolar lavage fluid samples came from patients with lung cancer and non-lung cancer. The composition and variations of the microbiota and metabolites in samples were explored using muti-omics technologies including 16S rRNA amplicon sequencing, metagenomics and metabolomics. RESULTS: The metabolomics analysis indicated that 40 different metabolites, such as 9,10-DHOME, sphingosine, and cysteinyl-valine, were statistically significant between two groups (VIP > 1 and P < 0.05). These metabolites were significantly enriched into 11 signal pathways including sphingolipid, autophagy and apoptosis signaling pathway (P < 0.05). The analysis of lung microbiota showed that significant changes reflected the decrease of microbial diversity, changes of distribution of microbial taxa, and variability of the correlation networks of lung microbiota in lung cancer patients. In particular, we found that oral commensal microbiota and multiple probiotics might be connected with the occurrence and progression of lung cancer. Moreover, our study found 3 metabolites and 9 species with significantly differences, which might be regarded as the potential clinical diagnostic markers associated with lung cancer. CONCLUSIONS: Lung microbiota and metabolites might play important roles in the pathogenesis of lung cancer, and the altered metabolites and microbiota might have the potential to be clinical diagnostic markers and therapeutic targets associated with lung cancer.