High temperature and ozone co-exposure induces cardiovascular damage in mice: Insights from gut microbiome and plasma metabolomics

Epidemiological studies have demonstrated associations between heat waves, ozone (O3) pollution, and cardiovascular morbidity and mortality. High temperature (HT) and higher levels of O3 usually co-exist in the atmosphere. However, few studies have investigated the adverse effects of HT and O3 co-ex...

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Main Authors: Qiong Wu, Fei Xu, Yishu Yang, Aogang Zhang, Han Sun, Lin Yang, Shuaiqi Zhao, Yuling Zeng, Mengxin Wang, Saige Shi, Fengquan Zhang, Zhen An, Juan Li, Huijun Li, Hui Wu, Laibao Zhuo, Jie Song, Wen Chen, Weidong Wu
Format: Article
Language:English
Published: Elsevier 2025-07-01
Series:Ecotoxicology and Environmental Safety
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Online Access:http://www.sciencedirect.com/science/article/pii/S0147651325006591
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author Qiong Wu
Fei Xu
Yishu Yang
Aogang Zhang
Han Sun
Lin Yang
Shuaiqi Zhao
Yuling Zeng
Mengxin Wang
Saige Shi
Fengquan Zhang
Zhen An
Juan Li
Huijun Li
Hui Wu
Laibao Zhuo
Jie Song
Wen Chen
Weidong Wu
author_facet Qiong Wu
Fei Xu
Yishu Yang
Aogang Zhang
Han Sun
Lin Yang
Shuaiqi Zhao
Yuling Zeng
Mengxin Wang
Saige Shi
Fengquan Zhang
Zhen An
Juan Li
Huijun Li
Hui Wu
Laibao Zhuo
Jie Song
Wen Chen
Weidong Wu
author_sort Qiong Wu
collection DOAJ
description Epidemiological studies have demonstrated associations between heat waves, ozone (O3) pollution, and cardiovascular morbidity and mortality. High temperature (HT) and higher levels of O3 usually co-exist in the atmosphere. However, few studies have investigated the adverse effects of HT and O3 co-exposure on cardiovascular system. Therefore, this study aimed to examine the effects of HT and O3 co-exposure on biomarkers of cardiovascular damage and potential mechanisms. Sixty-four healthy SPF male C57BL/6N mice, aged 8 weeks, were randomly allocated into four groups: control, O3, HT, and co-exposure (HT+O3). Mice inhaled filtered air or 1 ppm O3 at 24 °C or 36 °C, respectively, 4 h/day, for 5 consecutive days. Following the exposure, the biological samples of mice were collected for examination of biomarkers of cardiovascular disorders. Exposure to HT+O3 exacerbated cardiovascular pathological damage induced by HT or O3 alone. Compared to the control, the co-exposure group caused significant alterations of cardiovascular biomarkers. Moreover, co-exposure enhanced reduction of Lactobacillus and Ruminococcus and increases in Prevotella and Alistipe abundances induced by either HT or O3. Moreover, co-exposure also promoted O3-induced plasma metabolic disorder and these metabolites were enriched in multiple metabolic pathways typified by steroid hormone biosynthesis, biosynthesis of unsaturated fatty acids, and phenylalanine metabolism, among others. Spearman correlation analysis indicated that alterations of gut microbiota were significantly correlated with biomarkers of cardiovascular damage as well as plasma metabolic disorder. Exposure to HT and O3 leads to cardiovascular damage, which possibly implicates gut microbial dysbiosis and plasma metabolic disorder.
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spelling doaj-art-07f81b6c312a433182a5fcbbf44c806d2025-08-20T02:32:23ZengElsevierEcotoxicology and Environmental Safety0147-65132025-07-0129911832310.1016/j.ecoenv.2025.118323High temperature and ozone co-exposure induces cardiovascular damage in mice: Insights from gut microbiome and plasma metabolomicsQiong Wu0Fei Xu1Yishu Yang2Aogang Zhang3Han Sun4Lin Yang5Shuaiqi Zhao6Yuling Zeng7Mengxin Wang8Saige Shi9Fengquan Zhang10Zhen An11Juan Li12Huijun Li13Hui Wu14Laibao Zhuo15Jie Song16Wen Chen17Weidong Wu18Henan International Collaborative Laboratory for Health Effects and Intervention of Air Pollution, School of Public Health, Xinxiang Medical University, Xinxiang, Henan Province 453003, ChinaHenan International Collaborative Laboratory for Health Effects and Intervention of Air Pollution, School of Public Health, Xinxiang Medical University, Xinxiang, Henan Province 453003, ChinaHenan International Collaborative Laboratory for Health Effects and Intervention of Air Pollution, School of Public Health, Xinxiang Medical University, Xinxiang, Henan Province 453003, ChinaHenan International Collaborative Laboratory for Health Effects and Intervention of Air Pollution, School of Public Health, Xinxiang Medical University, Xinxiang, Henan Province 453003, ChinaHenan International Collaborative Laboratory for Health Effects and Intervention of Air Pollution, School of Public Health, Xinxiang Medical University, Xinxiang, Henan Province 453003, ChinaHenan International Collaborative Laboratory for Health Effects and Intervention of Air Pollution, School of Public Health, Xinxiang Medical University, Xinxiang, Henan Province 453003, ChinaHenan International Collaborative Laboratory for Health Effects and Intervention of Air Pollution, School of Public Health, Xinxiang Medical University, Xinxiang, Henan Province 453003, ChinaHenan International Collaborative Laboratory for Health Effects and Intervention of Air Pollution, School of Public Health, Xinxiang Medical University, Xinxiang, Henan Province 453003, ChinaHenan International Collaborative Laboratory for Health Effects and Intervention of Air Pollution, School of Public Health, Xinxiang Medical University, Xinxiang, Henan Province 453003, ChinaHenan International Collaborative Laboratory for Health Effects and Intervention of Air Pollution, School of Public Health, Xinxiang Medical University, Xinxiang, Henan Province 453003, ChinaHenan International Collaborative Laboratory for Health Effects and Intervention of Air Pollution, School of Public Health, Xinxiang Medical University, Xinxiang, Henan Province 453003, ChinaHenan International Collaborative Laboratory for Health Effects and Intervention of Air Pollution, School of Public Health, Xinxiang Medical University, Xinxiang, Henan Province 453003, ChinaHenan International Collaborative Laboratory for Health Effects and Intervention of Air Pollution, School of Public Health, Xinxiang Medical University, Xinxiang, Henan Province 453003, ChinaHenan International Collaborative Laboratory for Health Effects and Intervention of Air Pollution, School of Public Health, Xinxiang Medical University, Xinxiang, Henan Province 453003, ChinaHenan International Collaborative Laboratory for Health Effects and Intervention of Air Pollution, School of Public Health, Xinxiang Medical University, Xinxiang, Henan Province 453003, ChinaHenan International Collaborative Laboratory for Health Effects and Intervention of Air Pollution, School of Public Health, Xinxiang Medical University, Xinxiang, Henan Province 453003, ChinaHenan International Collaborative Laboratory for Health Effects and Intervention of Air Pollution, School of Public Health, Xinxiang Medical University, Xinxiang, Henan Province 453003, ChinaDepartment of Toxicology, School of Public Health, Sun Yat-sen University, Guangzhou, Guangdong 510080, ChinaHenan International Collaborative Laboratory for Health Effects and Intervention of Air Pollution, School of Public Health, Xinxiang Medical University, Xinxiang, Henan Province 453003, China; Correspondence to: School of Public Health, Xinxiang Medical University, Xinxiang, Henan Province 453003, China.Epidemiological studies have demonstrated associations between heat waves, ozone (O3) pollution, and cardiovascular morbidity and mortality. High temperature (HT) and higher levels of O3 usually co-exist in the atmosphere. However, few studies have investigated the adverse effects of HT and O3 co-exposure on cardiovascular system. Therefore, this study aimed to examine the effects of HT and O3 co-exposure on biomarkers of cardiovascular damage and potential mechanisms. Sixty-four healthy SPF male C57BL/6N mice, aged 8 weeks, were randomly allocated into four groups: control, O3, HT, and co-exposure (HT+O3). Mice inhaled filtered air or 1 ppm O3 at 24 °C or 36 °C, respectively, 4 h/day, for 5 consecutive days. Following the exposure, the biological samples of mice were collected for examination of biomarkers of cardiovascular disorders. Exposure to HT+O3 exacerbated cardiovascular pathological damage induced by HT or O3 alone. Compared to the control, the co-exposure group caused significant alterations of cardiovascular biomarkers. Moreover, co-exposure enhanced reduction of Lactobacillus and Ruminococcus and increases in Prevotella and Alistipe abundances induced by either HT or O3. Moreover, co-exposure also promoted O3-induced plasma metabolic disorder and these metabolites were enriched in multiple metabolic pathways typified by steroid hormone biosynthesis, biosynthesis of unsaturated fatty acids, and phenylalanine metabolism, among others. Spearman correlation analysis indicated that alterations of gut microbiota were significantly correlated with biomarkers of cardiovascular damage as well as plasma metabolic disorder. Exposure to HT and O3 leads to cardiovascular damage, which possibly implicates gut microbial dysbiosis and plasma metabolic disorder.http://www.sciencedirect.com/science/article/pii/S0147651325006591High temperatureOzoneGut microbiotaPlasmaMetabolomics
spellingShingle Qiong Wu
Fei Xu
Yishu Yang
Aogang Zhang
Han Sun
Lin Yang
Shuaiqi Zhao
Yuling Zeng
Mengxin Wang
Saige Shi
Fengquan Zhang
Zhen An
Juan Li
Huijun Li
Hui Wu
Laibao Zhuo
Jie Song
Wen Chen
Weidong Wu
High temperature and ozone co-exposure induces cardiovascular damage in mice: Insights from gut microbiome and plasma metabolomics
Ecotoxicology and Environmental Safety
High temperature
Ozone
Gut microbiota
Plasma
Metabolomics
title High temperature and ozone co-exposure induces cardiovascular damage in mice: Insights from gut microbiome and plasma metabolomics
title_full High temperature and ozone co-exposure induces cardiovascular damage in mice: Insights from gut microbiome and plasma metabolomics
title_fullStr High temperature and ozone co-exposure induces cardiovascular damage in mice: Insights from gut microbiome and plasma metabolomics
title_full_unstemmed High temperature and ozone co-exposure induces cardiovascular damage in mice: Insights from gut microbiome and plasma metabolomics
title_short High temperature and ozone co-exposure induces cardiovascular damage in mice: Insights from gut microbiome and plasma metabolomics
title_sort high temperature and ozone co exposure induces cardiovascular damage in mice insights from gut microbiome and plasma metabolomics
topic High temperature
Ozone
Gut microbiota
Plasma
Metabolomics
url http://www.sciencedirect.com/science/article/pii/S0147651325006591
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