Localized Microbial–Immunometabolic Interactions and Early Lung Cancer

The composition of lower airway microbiome has been linked to the development and progression of non-small cell lung cancer (NSCLC). Recent research has transitioned from viewing the lung microbiome as a bystander to a central player in carcinogenesis. Enrichment of oral commensals, specifically Veillonella, Prevotella, and Streptococcus, in the lower airways is associated with upregulated oncogenic pathways and increased inflammatory immune tone. A new integrative multiomic analysis by Weinberg and colleagues involving patients with early-stage NSCLC further supports these associations. By comparing bronchoalveolar lavage fluid from tumor-affected lobes against unaffected lobes within the same patient, researchers identified a localized microbial-immunometabolic niche. Key findings include an enrichment of the Veillonella-Streptococcus-Prevotella taxa and the metabolic byproduct stearic acid (SA) in tumor-affected sites. Ex vivo, SA stimulates macrophages into a "polyfunctional" state, secreting pro-inflammatory cytokines like MIP-1β and RANTES. This secretome could induce neoplastic transformation in lung epithelial cells, facilitating anchorage-independent growth. These insights shift paradigms toward metabolically driven innate immune reprogramming induced by the lung microbiome as an early event in tumor development, offering new strategies for diagnosis, therapy monitoring, and preventive interventions. See related article by Weinberg et al., p. 229 .