Abstract
OBJECTIVE: Our research has pinpointed the gut microbiome's role in the progression of various pathological types of non-small cell lung cancer (NSCLC). Nonetheless, the characteristics of the gut microbiome and its metabolites across different clinical stages of NSCLC are yet to be fully understood. The current study seeks to explore the distinctive gut flora and metabolite profiles of NSCLC patients across varying TNM stages. METHODS: The research team gathered stool samples from 52 patients diagnosed with non-small cell lung cancer (NSCLC) and 29 healthy individuals. Subsequently, they performed 16S rRNA gene amplification sequencing and untargeted gas/liquid chromatography-mass spectrometry metabolomics analysis. RESULTS: The study revealed that the alpha-diversity of the gut microbiome in NSCLC patients at different stages did not exhibit statistically significant differences. Notably, Lachnospira and Blautia were more abundant in healthy controls. The distribution of gut microbial species in patients with varying stages of NSCLC was uneven, with Bacteroides and Bacteroidaceae being most prevalent in stage T2, and Prevotella dominating in stage T4. Levels of Ruminococcus gnavus were notably elevated in stages N3 and M. The genus levels of Klebsiella, Parabacteroides, and Tannerellaceae were higher in stage II patients. Rodentibacter was the bacterium with increased levels in stage III NSCLC patients. Further metabolomics studies revealed significantly elevated levels of quinic acid and 3-hydroxybenzoic acid in the healthy control group. In contrast, Stage I+II non-small cell lung cancer (NSCLC) patients exhibited reduced levels of L-cystathionine. Notably, quinic acid, phthalic acid, and L-lactic acid were observed to be increased in Stage III+IV NSCLC patients. CONCLUSION: Compared to the analysis of a single microbial dataset, this study provides deeper functional insights by incorporating comprehensive metabolomic profiling. This approach demonstrates that both the gut microbiome and associated metabolites are altered in NSCLC patients across different clinical stages. Our findings may offer novel perspectives on the pathogenesis of NSCLC at various TNM stages. Further research is warranted to validate and clinically apply these potential biomarkers.