Metabolite correlation permutation after mice acute exposure to PM2.5: Holistic exploration of toxicometabolomics by network analysis

Hao Chang; Xi Zhang; Zhonghua Lu; Biling Gao; Heqing Shen

doi:10.1016/j.envpol.2024.124128

Metabolite correlation permutation after mice acute exposure to PM_2.5: Holistic exploration of toxicometabolomics by network analysis

Environ Pollut. 2024 May 8:352:124128. doi: 10.1016/j.envpol.2024.124128. Online ahead of print.

Authors

Hao Chang¹, Xi Zhang², Zhonghua Lu¹, Biling Gao¹, Heqing Shen³

Affiliations

¹ State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory & State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen, 361102, PR China.
² Key Laboratory of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen, 361021, PR China.
³ State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory & State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen, 361102, PR China; Women and Children's Hospital, School of Medicine, Xiamen University, Xiamen, 361003, PR China. Electronic address: hqshen@xmu.edu.cn.

PMID: 38729510
DOI: 10.1016/j.envpol.2024.124128

Abstract

Many environmental toxicants can cause systemic effects, such as fine particulate matter (PM_2.5), which can penetrate the respiratory barrier and induce effects in multiple tissues. Although metabolomics has been used to identify biomarkers for PM_2.5, its multi-tissue toxicology has not yet been explored holistically. Our objective is to explore PM_2.5 induced metabolic alterations and unveil the intra-tissue responses along with inter-tissue communicational effects. In this study, following a single intratracheal instillation of multiple doses (0, 25, and 150 μg as the control, low, and high dose), non-targeted metabolomics was employed to evaluate the metabolic impact of PM_2.5 across multiple tissues. PM_2.5 induced tissue-specific and dose-dependent disturbances of metabolites and their pathways. The remarkable increase of both intra- and inter-tissue correlations was observed, with emphasis on the metabolism connectivity among lung, spleen, and heart; the tissues' functional specificity has marked their toxic modes. Beyond the inter-status comparison of the metabolite fold-changes, the current correlation network built on intra-status can offer additional insights into how the multiple tissues and their metabolites coordinately change in response to external stimuli such as PM_2.5 exposure.

Keywords: Acute effects; Fine particulate matter (PM(2.5)); Metabolomics; Multi-tissue analysis; Toxicometabolomics.