Guangdong-Hong Kong-Macao Joint Laboratory for Contaminants Exposure and Health, School of Environmental Science and Engineering, Institute of Environmental Health and Pollution Control, Guangdong University of Technology, Guangzhou 510006, Guangdong, China.
State Key Laboratory of Environmental and Biological Analysis, Department of Chemistry, Hong Kong Baptist University, Hong Kong, China.
Sci Total Environ. 2023 Jun 1;875:162615. doi: 10.1016/j.scitotenv.2023.162615. Epub 2023 Mar 4.
Phthalate esters (PAEs) are one of the significant classes of emerging contaminants that are increasingly detected in environmental and human samples. Nevertheless, the current toxicity studies rarely report how PAEs affect the cardiovascular system, especially in obese individuals. In this study, diet-induced obese mice and corresponding normal mice were exposed to di(2-ethylhexyl) phthalate (DEHP) by oral gavage at environmentally relevant concentrations and key characteristics of cardiovascular risk were examined. The 16S rRNA and high-resolution mass spectrometry were used to investigate the alterations in the gut microbial profile and metabolic homeostasis. The results indicated that the cardiovascular system of fat individuals was more susceptible to DEHP exposure than mice in the lean group. 16S rRNA-based profiling and correlation analysis collectively suggested DEHP-induced gut microbial remodeling in fed a high-fat diet mice, represented by the abundance of the genus Faecalibaculum. Using metagenomic approaches, Faecalibaculum rodentium was identified as the top-ranked candidate bacterium. Additionally, metabolomics data revealed that DEHP exposure altered the gut metabolic homeostasis of arachidonic acid (AA), which is associated with adverse cardiovascular events. Finally, cultures of Faecalibaculum rodentium were treated with AA in vitro to verify the role of Faecalibaculum rodentium in altering AA metabolism. Our findings provide novel insights into DEHP exposure induced cardiovascular damage in obese individuals and suggest that AA could be used as a potential modulator of gut microbiota to prevent related diseases.
邻苯二甲酸酯（PAEs）是一类新兴的污染物，在环境和人体样本中越来越多地被检测到。然而，目前的毒性研究很少报告 PAEs 如何影响心血管系统，特别是在肥胖人群中。在这项研究中，通过口服灌胃将饮食诱导肥胖的小鼠和相应的正常小鼠暴露于环境相关浓度的邻苯二甲酸二（2-乙基己基）酯（DEHP），并检查了心血管风险的关键特征。16S rRNA 和高分辨率质谱用于研究肠道微生物群谱和代谢平衡的变化。结果表明，肥胖个体的心血管系统比瘦组小鼠更容易受到 DEHP 暴露的影响。基于 16S rRNA 的分析和相关性分析共同表明，DEHP 诱导了高脂肪饮食小鼠的肠道微生物重塑，以 Faecalibaculum 属的丰度为代表。使用宏基因组学方法，鉴定出 Faecalibaculum rodentium 是排名最高的候选细菌。此外，代谢组学数据显示，DEHP 暴露改变了 AA 的肠道代谢平衡，这与不良心血管事件有关。最后，体外培养 Faecalibaculum rodentium 并用 AA 处理，以验证 Faecalibaculum rodentium 在改变 AA 代谢中的作用。我们的研究结果为 DEHP 暴露引起肥胖个体心血管损伤提供了新的见解，并表明 AA 可用作肠道微生物群的潜在调节剂，以预防相关疾病。
