Microbial metabolites and the gut-lung axis in non-small cell lung cancer immunotherapy: evidence boundaries and translational implications

The article addresses the role of gut microbiome and microbial metabolites in the treatment of non-small cell lung cancer (NSCLC) using immune checkpoint inhibitors (ICIs). A structured review includes studies with patient numbers ranging from 37 to 556 individuals, including a phase III chemoimmunotherapy cohort with 270 baseline fecal samples. Clinical evidence shows inconsistent associations between microbiome diversity, Akkermansia-related states, functional microbiome features, and patient survival. Mechanistic studies support the role of short-chain fatty acids, bile acids, tryptophan-related metabolites, and inosine. However, few studies connect microbiome, metabolite, immune, and clinical outcome data within the same patients. The authors conclude that microbiome signals are better suited for prospective validation and clinical trial design than for routine testing outside regulated studies.