Environmental endocrine disrupting chemical-DEHP exposure-provoked biotoxicity about microbiota-gut-mammary axis in lactating mice via multi-omics technologies

IF 10.3 1区环境科学与生态学 Q1 ENVIRONMENTAL SCIENCES

Environment International Pub Date : 2024-11-01 DOI:10.1016/j.envint.2024.109130

Xiaolong Xu, Yonglong He, Zefang Cheng, Haoyuan Zhang, Yijian Chu, Zhewei Wang, Xiaopeng An

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Abstract

Plastics, pervasive in humans and nature, often contain Di (2-ethylhexyl) phthalate (DEHP) that enhance plastic’s elasticity. However, DEHP is an environmental endocrine disruptor, affecting organisms upon exposure. Understanding mammary gland development in lactating females is crucial for offspring nourishment and dairy production. Employing multi-omics technology, this study aimed to uncover DEHP’s impact on the microbial–gut–mammary axis. Forty mice were exposed to varying DEHP doses for 18 d. We performed 16S sequencing, metabolomics, mammary tissue observation, and gene expression profiling. Results revealed DEHP’s influence on microbial diversity, with increased Lactobacillus abundance and reduced Proteobacteria, alongside colonic inflammation. Elevated GMP and adenosine 5′-monophosphate levels in the bloodstream were noted, while ascorbic acid, glycitein, and others decreased. MEHP, a DEHP metabolite, damaged mammary tissues, inhibiting ERK1/2 phosphorylation, triggering apoptosis and ferroptosis. These findings unveil potential therapeutic targets for DEHP-induced chronic toxicity in humans and animals, aiding dairy livestock health and human well-being. This study underscores the importance of understanding the adverse effects of DEHP exposure on mammalian systems.

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通过多组学技术研究环境内分泌干扰化学物质--DEHP暴露引起的哺乳小鼠微生物群-肠道-乳腺轴的生物毒性

塑料在人类和自然界中普遍存在，通常含有邻苯二甲酸二（2-乙基己酯）（DEHP），可增强塑料的弹性。然而，DEHP 是一种环境内分泌干扰物，生物一旦接触就会受到影响。了解哺乳期雌性动物乳腺的发育对后代的营养和乳制品生产至关重要。本研究采用多组学技术，旨在揭示DEHP对微生物-肠道-乳腺轴的影响。我们进行了 16S 测序、代谢组学、乳腺组织观察和基因表达谱分析。结果表明，DEHP 会影响微生物多样性，增加乳酸杆菌的数量，减少变形杆菌，同时引发结肠炎症。血液中的 GMP 和腺苷-5′-单磷酸水平升高，而抗坏血酸、甘氨酸和其他物质则下降。DEHP的代谢物MEHP会破坏乳腺组织，抑制ERK1/2磷酸化，引发细胞凋亡和铁变态反应。这些发现揭示了DEHP诱导的人类和动物慢性毒性的潜在治疗靶点，有助于奶畜健康和人类福祉。这项研究强调了了解 DEHP 暴露对哺乳动物系统不良影响的重要性。

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来源期刊

Environment International 环境科学-环境科学

CiteScore

21.90

自引率

3.40%

发文量

734

审稿时长

2.8 months

期刊介绍： Environmental Health publishes manuscripts focusing on critical aspects of environmental and occupational medicine, including studies in toxicology and epidemiology, to illuminate the human health implications of exposure to environmental hazards. The journal adopts an open-access model and practices open peer review. It caters to scientists and practitioners across all environmental science domains, directly or indirectly impacting human health and well-being. With a commitment to enhancing the prevention of environmentally-related health risks, Environmental Health serves as a public health journal for the community and scientists engaged in matters of public health significance concerning the environment.