Abstract

Lung cancer remains a leading global health challenge, characterized by uncontrolled proliferation and lower survival rates despite advances in chemotherapy. Persistent issues include drug resistance, poor bioavailability, and toxicity. Emerging evidence suggests that dysbiosis of gut microbiota is involved in lung cancer development, increasing interest in probiotics to restore homeostasis. This review proposes a postbiotic-centric lung cancer framework, shifting the conceptual focus from live bacteria to the therapeutic potential of probiotic-derived metabolites. We elucidate the triadic dysbiosis patterns across oral, gut, and lung environments in non-small cell lung cancer and detail a bioactive profile consisting of sulfur-rich exopolysaccharides, bacteriocins, and non-ribosomal peptides. These compounds exert potential anti-proliferative effects by modulating intrinsic and extrinsic apoptotic pathways, specifically activating the Caspase-3/7/9 cascades and inhibiting oncogenic signaling by nuclear factor NF-κB and Wnt/β-catenin. Furthermore, we provide a critical appraisal of present translational gaps, including the methodological limitations of monolayer A549 models, the risk of horizontal gene transfer, and the pharmacokinetic challenges of aerosolized delivery. This review directly supports Sustainable Development Goal 3, promotes scalable, low-toxicity microbiological innovations for equitable lung cancer management in high-risk and resource-limited regions.

Key words: Gut–lung axis, Microbial dysbiosis, Non-Small Cell Lung Cancer, Postbiotics, Global Health