Association of PM2.5 and its elemental components with plasma metabolome in healthy older adults: Evidence from epidemiological and experimental studies

Previous studies have found that exposure to fine particulate matter (PM 2.5 ) is associated with metabolic alterations, but the specific effects of its composition on metabolic changes remain unclear. To identify key metabolites associated with PM 2.5 exposure and its elemental components, with validation through animal experiments. A total of 112 healthy older adults were enrolled in the cross-sectional study between winter 2020 and summer 2021. Individual PM 2.5 exposure levels were quantified by personal samplers, and ten trace elements in PM 2.5 were analyzed using inductively coupled plasma mass spectrometry (ICP-MS). Animal experiments were conducted on male rats to validate the associations between PM 2.5 , its elemental composition, and metabolomic changes. Fasting venous blood samples from participants and rat heart blood were collected for non-targeted metabolomic analysis using Orthogonal Projections to Latent Structures-Discriminant Analysis (OPLS-DA) and pathway enrichment analysis via MetaboAnalyst 5.0. PM 2.5 exposure was significantly associated with changes in 218 plasma metabolites (p < 0.05). Non-targeted metabolomic analysis identified 29 and 7 metabolic pathways associated with PM 2.5 exposure and trace elements, respectively, primarily associated with lipid metabolism, including linoleic acid metabolism. Significant overlaps of metabolomic pathways were observed in chromium (Cr) and PM 2.5 . A total of 29 human metabolic pathways affected by PM 2.5 exposure were identified in the human study, of which 17 common to both humans and rats, including glycerophospholipid metabolism. These metabolites and pathways are related to metabolic disorders, with PM 2.5 -related metabolites showing associations with diseases like diabetes ( P = 0.049). These findings highlight the important role of Cr in PM 2.5 -induced metabolic changes, emphasizing the need to monitor specific PM 2.5 components for assessing health risks and informing public health policies. • PM2.5 exposure linked to alter lipid metabolism, particularly linoleic acid pathways. • Chromium in PM2.5 may be a key component affecting metabolic pathways. • High PM2.5 exposure was linked to aluminum, chromium, selenium, and cadmium levels. • Chromium and arsenic affected glycerophospholipid and arachidonic acid metabolism. • Animal model validates human findings with dose-dependent pathological changes