Sub-chronic exposure to ambient ozone induced liver and lung damage: raveled by lung-liver axis

Abstract

Ozone (O₃) has become a major air pollutant worldwide, posing an alarming threat to public health. However, whether the exposure to O₃ induces liver and lung damage remains unclear, alongside the underlying mechanisms. In this study, the mice were exposed to environmentally-relevant concentrations of O₃ for 30 d, alongside the systemic analysis of the injuries in lungs and livers. The results revealed that O₃ exposure could reduce weight gain and induce histopathological damage in both lungs and livers, accompanied by dysregulated oxidative stress-related genes and elevated pro-inflammatory factors. Additionally, the lung microbiome analysis demonstrated that the microbial abundance was decreased and community structure was altered, and it was indicated by the network analysis that the complexity of the microbial network was diminished. Besides, the aspartate aminotransferase (AST) activity, malondialdehyde (MDA), and Fe²⁺ levels were found to be elevated after O₃ exposure by the hepatic profile assessment, accompanied by depleted glutathione (GSH) both in liver and plasma. These alterations were associated with a ferroptosis process in the liver, and it was confirmed by lipidomics that the most significantly impacted processes were ferroptosis-related. Additionally, multi-omics mediation analysis demonstrated that lung injury could mediate liver lipid dysregulation through lung microbiota. These findings provide novel mechanistic insights into the toxicological mechanism of O₃ via the lung-liver axis.

Graphical abstract

Keywords

Ozone / Environmentally-relevant O ₃ concentrations / Lung microbial / Liver ferroptosis / Lung-liver axis

Highlight

	● O3 reduced lung microbiota α -diversity and network stability.
	● O3 induced lung dysbiosis and pulmonary injury.
	● O3 exposure impaired weight gain and elevated hepatic AST, MDA, and Fe2+.
	● Lung injury mediated liver lipid dysregulation via lung microbiota modulation.

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