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Unraveling Metabolic Alterations in Avian Influenza Exposed Individuals A Non Targeted Metabolomics Approach

ABSTRACT: Avian influenza poses a continuous public health threat, particularly to individuals with occupational exposure to poultry such as farm workers, live animal market employees, and processing plant staff. To investigate the systemic metabolic effects of such exposure, we applied an untargeted liquid chromatography mass spectrometry (LC MS) based metabolomics approach to analyze serum samples from occupationally exposed individuals and healthy controls. Multivariate statistical analysis revealed clear separation between the two groups, with stable clustering of quality control samples indicating high analytical reproducibility. Pathway enrichment and topology analyses identified several significantly altered metabolic pathways in the exposed group, most notably alanine, aspartate and glutamate metabolism and tryptophan metabolism, both of which are closely linked to immune regulation, energy metabolism, and host-pathogen interactions. In addition, lipidomic profiling revealed a pronounced increase in lysophosphatidylcholine (LPC) levels and a concurrent decrease in phosphatidylcholine (PC) species in exposed individuals, suggesting inflammation-associated lipid remodeling. These findings provide novel insights into the metabolic disruptions associated with avian influenza exposure and highlight potential serum biomarkers for early detection and health risk assessment in high risk occupational populations.

INSTRUMENT(S): Q Exactive Plus

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: maoshuoqin

PROVIDER: MSV000098297 | MassIVE | Tue Jun 24 00:26:00 BST 2025

REPOSITORIES: MassIVE

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Project description:Background: Pre-existing metabolic diseases may predispose individuals to particulate matter (PM)-induced adverse health effects. However, the differences in susceptibility of various metabolic diseases to PM-induced lung injury and their underlying mechanisms have yet to be fully elucidated. Results: Type 1 diabetes (T1D) or diet-induced obesity (DIO) murine models were generated by injection of streptozotocin or feeding a 45% high-fat diet for 10 weeks, respectively, and subjected to 4-week real-ambient PM exposure in Shijiazhuang, China (mean PM2.5 concentration 95.77 μg/m3). Pulmonary and systemic injury was assessed, and the underlying mechanisms were explored through transcriptomics analysis. Compared with normal diet (ND)-fed mice, T1D mice exhibited severe hyperglycemia with a blood glucose of 350 mg/dL, while DIO mice displayed moderate obesity and marked dyslipidemia with a slightly elevated blood glucose of 180 mg/dL. T1D and DIO mice were susceptible to PM-induced lung injury, manifested by inflammatory changes such as interstitial neutrophil infiltration and alveolar septal thickening. Notably, the acute lung injury scores were higher by 79.57% and 48.47%, respectively, than that of ND-fed mice. Lung transcriptome analysis revealed that increased susceptibility to PM exposure was associated with perturbations in multiple pathways including glucose and lipid metabolism, inflammatory responses, oxidative stress, cellular senescence, and tissue remodeling. Functional experiments confirmed that changes in biomarkers of macrophage (F4/80), lipid peroxidation (4-HNE), cellular senescence (SA-β-gal), and airway repair (CCSP) were most pronounced in the lungs of PM-exposed T1D mice. Furthermore, pathways associated with xenobiotic metabolism showed metabolic state- and tissue-specific perturbation patterns. Upon PM exposure, activation of nuclear receptor (NR) pathways and inhibition of the glutathione (GSH)-mediated detoxification pathway were evident in the lungs of T1D mice, and a significant upregulation of NR pathways was present in the livers of T1D mice. Conclusions: These differences might contribute to differential susceptibility to PM exposure between T1D and DIO mice. These findings provide new insights into the health risk assessment of PM exposure in populations with metabolic diseases.

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Unraveling Metabolic Alterations in Avian Influenza Exposed Individuals A Non Targeted Metabolomics Approach

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