Abstract
This study integrated data from the Comparative Toxicogenomics Database (CTD) to investigate the molecular pathways by which selected dietary nutrients modulate the adverse effects of indoor air pollutants on asthma pathogenesis. Our analysis of 1199 curated chemicals-genes-phenotypes-disease interaction modules (CTD Tetramers) revealed about 60 key genes and 236 phenotypes involved in oxidative stress, inflammation, apoptosis, proliferation, and immune regulation. Nutrients including gamma-tocopherol, vitamin A, resveratrol, theophylline, and zinc were found to influence these molecular targets. Notably, resveratrol significantly altered the expression of 51 genes (including both up- and down-regulation) and modulated 187 phenotypes, suggesting a pivotal role in attenuating pro-inflammatory cytokine production and reducing oxidative damage. Further anatomical and systems-level analysis demonstrated that both pollutants and these nutritional factors affect critical components of the respiratory system, and the immune network. The modulation of key mediators such as IL6 and TNF supports the dual functions of these nutrients in managing acute inflammation and preventing chronic airway remodeling. Our findings provide molecular evidence that nutritional interventions hold promise as a complementary strategy for mitigating asthma induced by indoor air pollutants. Although our results support the protective effects of the examined nutrients, further in vitro and in vivo studies are necessary to detail the contributions of other dietary components such as flavonoids, vitamin C, and vitamin D. Overall, this study establishes a framework that links environmental exposures with targeted nutritional approaches, and it paves the way for future clinical trials and nutraceutical therapies in respiratory health. These results underscore the potential of diet-based interventions as a tool in global respiratory health improvement.