纳米塑料和双酚A对斑马鱼脂质代谢的跨代影响：通过mTOR途径破坏肠道微生物-肝脏轴

IF 4.1 2区环境科学与生态学 Q1 MARINE & FRESHWATER BIOLOGY

Aquatic Toxicology Pub Date : 2025-05-05 DOI:10.1016/j.aquatox.2025.107401

Zikai Liu , Lanlan Li , Bingbing Sun , Yinhao Ding , Yan lv , Qing Wu , Sujuan Zhao , Xiang Zhang , Tong Shen

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引用次数: 0

摘要

肠肝轴对机体健康至关重要。纳米塑料（NPs）和双酚A （BPA）会损害斑马鱼的肠道和肝脏，但它们对肠道-肝脏轴的综合影响和跨代效应尚不清楚。在这项研究中，F0斑马鱼暴露于NPs和/或BPA 28天。检测F0、F1、F2斑马鱼的脂质指标及后代的发育指标。采用16S rRNA测序和代谢组学技术对F0斑马鱼肠道菌群和肝脏代谢物进行分析，探讨其机制。将mTOR抑制剂Rapa注射到F0斑马鱼体内，研究mTOR通路在NPs和BPA暴露引起的脂质紊乱中的作用。结果表明，第0代斑马鱼暴露于NPs和BPA导致所有代斑马鱼脂质代谢紊乱，第1代和第2代斑马鱼发育异常。组学分析显示，NPs和BPA联合暴露显著加剧了F0斑马鱼肠道微生物群紊乱。非靶向代谢组学鉴定的差异代谢物在mTOR信号通路中富集。经Rapa干预后，各组F0斑马鱼的脂质紊乱得到改善。综上所述，NPs和BPA的联合暴露可能通过加剧F0斑马鱼肠道菌群-肝脏轴的失调，导致所有代斑马鱼的脂质紊乱和后代的异常发育。本研究的结果为NPs和BPA联合暴露诱导的跨代效应提供了机制见解。

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Transgenerational effects of Nanoplastics and bisphenol A on Zebrafish lipid metabolism: Disruption of the gut Microbiota-liver axis via mTOR pathway

The gut-liver axis is vital for organism health. Nanoplastics (NPs) and bisphenol A (BPA) can harm zebrafish intestines and livers, yet their combined impact on the gut-liver axis and transgenerational effects are unknown.

In this study, F0 zebrafish were exposed to NPs and/or BPA for 28 days. Lipid indices of F0, F1, and F2 zebrafish, as well as the developmental indices of offspring, were detected. 16S rRNA sequencing and metabolomics were used to analyze F0 zebrafish gut microbiota and liver metabolites, exploring underlying mechanisms. The mTOR inhibitor Rapa was injected into F0 zebrafish to examine the mTOR pathway's role in lipid disorders caused by NPs and BPA exposure.

The results showed that the exposure of F0 generation zebrafish to NPs and BPA led to lipid metabolism disorders in all generations of zebrafish and abnormal development in F1 and F2 zebrafish. Omics analysis revealed that the combined exposure to NPs and BPA significantly exacerbated the gut microbiota disorder in F0 zebrafish. The differential metabolites identified by untargeted metabolomics were enriched in the mTOR signaling pathway. After Rapa intervention, the lipid disorders in each group of F0 zebrafish were improved.

In summary, the combined exposure to NPs and BPA may lead to lipid disorders in all generations of zebrafish and abnormal development of offspring by exacerbating the dysregulation of the gut microbiota-liver axis in F0 zebrafish. The results of this study provide mechanistic insights into the transgenerational effects induced by the combined exposure to NPs and BPA.

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来源期刊

Aquatic Toxicology 环境科学-毒理学

CiteScore

7.10

自引率

4.40%

发文量

250

审稿时长

56 days

期刊介绍： Aquatic Toxicology publishes significant contributions that increase the understanding of the impact of harmful substances (including natural and synthetic chemicals) on aquatic organisms and ecosystems. Aquatic Toxicology considers both laboratory and field studies with a focus on marine/ freshwater environments. We strive to attract high quality original scientific papers, critical reviews and expert opinion papers in the following areas: Effects of harmful substances on molecular, cellular, sub-organismal, organismal, population, community, and ecosystem level; Toxic Mechanisms; Genetic disturbances, transgenerational effects, behavioral and adaptive responses; Impacts of harmful substances on structure, function of and services provided by aquatic ecosystems; Mixture toxicity assessment; Statistical approaches to predict exposure to and hazards of contaminants The journal also considers manuscripts in other areas, such as the development of innovative concepts, approaches, and methodologies, which promote the wider application of toxicological datasets to the protection of aquatic environments and inform ecological risk assessments and decision making by relevant authorities.