Influence of stage-specific and location-related intratumoral microbiota on prognosis and metabolic reprogramming in non-small cell lung cancer

Introduction: Mounting evidence links intratumoral microbiota to tumor progression and immune regulation, but stage-specific and location-related microbial characteristics in NSCLC remain insufficiently explored. Methods: Tumor and adjacent non-tumor tissues from 21 NSCLC patients were analyzed using 16S rRNA gene sequencing to profile the intratumoral microbiota. Functional pathway analysis, in vitro co-culture experiments (A549/HCC827 cells), and in vivo mouse models were employed to validate microbial functions. Results: Microbial composition exhibited significant heterogeneity by tumor stage (early vs. advanced) and anatomical location (upper vs. lower lobes). Bacteroides was identified as a key genus enriched in early-stage tumors and correlated with improved prognosis. Functional analysis revealed enrichment of tumor-associated microbiota in metabolic and biosynthetic pathways (e.g., carbon metabolism, amino acid biosynthesis). Further experiments demonstrated that Bacteroides significantly suppressed NSCLC cell proliferation, inhibited migration, and promoted apoptosis, with anti-tumor effects mediated by remodeling the tumor immune microenvironment. Discussion: These findings elucidate intricate associations between intratumoral microbiota, immune cell infiltration, and patient prognosis, highlighting Bacteroides as a potential prognostic biomarker and therapeutic target for NSCLC.