Environmental molybdenum exposure remodels pulmonary metabolic networks and disrupts oxidative stress-inflammation homeostasis, leading to lung injury and respiratory rhythm disturbances.

Environmental molybdenum (Mo) exposure is increasing worldwide. Notably, the lung has been recognized as a key target organ for heavy metal toxicity, yet the mechanisms underlying Mo-induced lung injury remain poorly understood. In this study, we systematically explored the mechanisms underlying Mo-induced lung injury through a multi-omics strategy integrating respiratory function evaluation, histopathology, biochemical analyses, proteomics, and metabolomics. Our results showed that Mo exposure led to significant accumulation of Mo in lung tissue, accompanied by increased respiratory rate and irregular breathing patterns, as well as marked histological damage. Biochemical analyses revealed that Mo exposure markedly impaired pulmonary antioxidant defenses, promoted oxidative stress, and activated inflammatory responses and apoptosis. Further proteomic and metabolomic analyses demonstrated widespread remodeling of protein expression and metabolic profiles in the lung following Mo exposure. Multi-omics integration identified a highly interconnected metabolic regulatory network centered on Glycine, serine and threonine metabolism, which is coordinated with beta-Alanine metabolism, Pentose phosphate pathway, Thiamine metabolism, and Cysteine and methionine metabolism. This network plays a key role in mediating lung injury, oxidative stress, inflammation, and apoptosis. Collectively, our findings demonstrate that environmental Mo exposure induces lung injury by remodeling metabolic networks and disrupts oxidative stress-inflammation homeostasis, providing new insights into the toxicological mechanisms of Mo.