Gut Microbiome and Immunotherapy Response in Lung Cancer: From Biomarker to Therapy

Immune checkpoint inhibitors have transformed non-small cell lung cancer treatment, yet responses remain unpredictable with current biomarkers. The gut microbiome has emerged as a key modulator of immunotherapy efficacy. This review synthesizes evidence on the gut microbiome's role in predicting and modulating immune checkpoint inhibitor response in non-small cell lung cancer. We examine associations between microbial diversity, taxonomy, and functional pathways with clinical outcomes including progression-free survival, overall survival, and treatment response. The microbiome influences immunotherapy through metabolite production, immune cell modulation, and tumor microenvironment interactions. Specific taxa including Akkermansia muciniphila, Bifidobacterium, and Ruminococcaceae correlate with improved outcomes. Functional pathway analysis outperforms taxonomic profiling, with urea cycle and short-chain fatty acid biosynthesis emerging as key determinants. Dietary interventions show promise, though probiotics may impair response. Concomitant medications including antibiotics, corticosteroids, and proton pump inhibitors significantly impact microbiome composition and outcomes. This review highlights microbiome-based biomarkers for patient stratification and therapeutic opportunities to improve clinical outcomes.