Microbiota-derived metabolites and components in lung cancer recurrence and metastasis

Lung cancer remains a leading cause of cancer mortality, and postoperative recurrence and metastatic progression continue to limit long-term survival. This review evaluates evidence that intratumoral and systemic microbiota may be associated with these outcomes through bioactive metabolites, microbial components, and extracellular vesicles. Metabolites such as butyrate, formate, and indole derivatives, together with components or products including lipopolysaccharide, β-glucan, and genotoxins, may influence epigenetic regulation, inflammatory signaling, immune remodeling, and metabolic programs. However, the evidence ranges from human lung cancer cohorts to preclinical and cross-cancer studies, and direct causal support for postoperative recurrence remains limited. Microbial and circulating microbiome DNA signatures are candidate biomarkers, whereas probiotics, targeted antimicrobials, fecal microbiota transplantation, and metabolite-directed interventions remain investigational. Priorities include rigorous low-biomass controls, spatial and longitudinal multi-omics, prospective biomarker validation, and carefully designed clinical trials.