Potential of Ginger Oil to Prevent 4‐(Methylnitrosamino)‐1‐(3‐Pyridyl)‐1‐Butanone‐Induced Lung Cancer Through Gut Microbiota Modulation and Inflammatory Response Inhibition

ABSTRACT Lung cancer remains the leading cause of cancer‐related mortality worldwide, with tobacco carcinogens such as 4‐(methylnitrosamino)‐1‐(3‐pyridyl)‐1‐butanone (NNK) playing a central role in its pathogenesis. Chemoprevention through dietary or natural compounds offers a promising strategy to mitigate cancer risk. Published studies have indicated that ginger oil (GIO), a bioactive extract from ginger, possesses various bioactivities, suggesting its potential for cancer chemopreventive. In this study, we aimed to investigate the lung cancer chemopreventive potential of GIO. An NNK‐induced lung cancer model in A/J mice was utilized to evaluate the preventive effect of GIO against lung cancer. Additionally, the potential mechanisms by which GIO might prevent NNK‐induced lung cancer were assessed using molecular biology techniques combined with multi‐omics. The results demonstrated that GIO decreased the number of lung tumors in the lungs of mice. Mechanistically, GIO exerts chemopreventive effects by modulating both the TLR4/NF‐κB and PPARγ/NF‐κB signaling axes, thereby suppressing downstream pro‐inflammatory mediators. Furthermore, GIO modulates gut microbiota composition and its metabolites. Critically, its lung chemopreventive efficacy against NNK‐induced lung carcinogenesis is partially dependent on microbiota‐mediated regulation. Overall, these findings underscore the nutritional value of GIO as a diet‐derived chemopreventive agent against lung cancer caused by tobacco carcinogens.