Metabolic alterations in lithium iron phosphate exposed workers and their mediation role in lung function decline: A...

Lithium iron phosphate (LiFePO4, LFP) is a pivotal cathode material in the lithium-ion battery industry. As the LFP market experiences rapid growth, there is an urgent need to assess the potential health hazards associated with occupational exposure to LFP. Herein, this study established the first cohort of LFP production workers and evaluated the effects of LFP exposure on lung function. Additionally, serum metabolic alterations were investigated using a combined untargeted metabolomics and lipidomics approach. Our results indicate that LFP exposure leads to a decline in pulmonary function, accompanied by elevated inflammatory markers. Metabolomics analysis revealed significant alterations in energy and amino acid metabolism, alongside an impairment of endogenous antioxidant systems. Furthermore, lipidomics demonstrated that LFP exposure perturbs sphingolipid and glycerophospholipid metabolism, pathways critically involved in inflammatory signaling and lung function impairment. Using Least Absolute Shrinkage and Selection Operator (LASSO) regression combined with the Boruta algorithm, we identified 12 key metabolites closely associated with lung function indicators. Bi-directional mediation analysis further revealed that five specific lipids significantly mediated the association between the systemic immune-inflammation index (SII) and forced vital capacity (FVC). These findings suggest that disrupted lipid metabolism acts as a crucial mediator in the inflammation-driven decline of lung function among LFP workers, providing a scientific basis for early occupational health risk assessment.