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Multiomics Profiling of Lung Tissues Reveals an Inflammation–Metabolism Axis Response to High-Temperature and Ozone Exposure

Year: 2026

Type: article

Abstract: Environmental stressors associated with heatwaves and ozone (O3) pollution are increasingly recognized as important contributors to metabolic and immune dysfunction, yet the underlying mechanisms remain incompletely understood. Using a newly developed “Temperature–Humidity–Ozone” Exposure System (THOES), the multiomics strategy was systematically applied to examine pulmonary responses due to O3 and high-temperature exposure in male mice and Apoe–/– mice. Microbial 16S rRNA sequencing analysis revealed that high temperature and ozone (HO) exposure and Apoe–/– caused gut microbiota dysbiosis and alterations in metabolic pathways, findings that were further supported by marked changes in lipid- and amino acid–related metabolites. Apoe–/– exacerbated disturbances in lipid-related metabolites linked to oxidative stress and fatty acid β-oxidation. Lipidomics identified remodeling of pulmonary lipid composition across major lipid classes, accompanied by a significant reduction in unsaturated lipid species following HO exposure and Apoe–/–. Complementary proteomic analysis revealed induction of acute-phase proteins and immune-related factors, alongside dysregulation of lipid transport proteins and mitochondrial respiratory components, highlighting activation of innate immune and defense-related pathways. These findings demonstrate that HO exposure induces coordinated immune, metabolic, and lipidomic alterations in the lung, with Apoe–/– conferring heightened susceptibility to disruption of metabolic and lipid homeostasis.

Source: Environment & Health

DOI: 10.1021/envhealth.6c00293