Lung cancer and the microbiome: Key bacterial players in carcinogenesis and therapy

Abstract

Lung cancer remains the leading cause of cancer-related mortality worldwide, with non–small cell lung cancer (NSCLC) constituting the majority of cases. Despite therapeutic advances in chemotherapy, targeted therapy, and immune checkpoint inhibitors (ICIs), treatment outcomes remain heterogeneous. Increasing evidence indicates that the human microbiome including the respiratory, gut, and intratumoral compartments plays a crucial role in lung carcinogenesis and therapeutic response. This narrative review synthesizes recent findings on the microbiome’s contribution to lung cancer biology and therapy. The healthy lung microbiota is characterized by low biomass yet consistent phyla composition, primarily Bacteroidetes and Firmicutes, while dysbiosis in lung cancer often features enrichment of Streptococcus, Veillonella, Prevotella, Haemophilus, and Fusobacterium. These taxa may drive carcinogenesis through immune modulation, chronic inflammation, metabolic signaling, and genotoxic or epigenetic alterations. Beyond the lung, gut microbial diversity and metabolites such as short-chain fatty acids (SCFAs) influence systemic immunity and modulate response to chemotherapy, targeted agents, and ICIs. Antibiotic-induced dysbiosis has been linked to reduced immunotherapy efficacy and shorter progression-free survival in NSCLC cohorts. Emerging microbiome-modulation strategies including probiotics, prebiotics, dietary interventions, fecal microbiota transplantation (FMT), and engineered bacterial therapeutics show promise as adjuncts to precision oncology. However, safety, reproducibility, and mechanistic causality remain major challenges. Collectively, evidence supports the microbiome as a dynamic regulator of lung cancer progression and therapy responsiveness. Future research should prioritize longitudinal, multi-omics investigations and controlled clinical trials to identify predictive microbial biomarkers and develop standardized, personalized microbiome-based interventions for lung cancer management.