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微/纳米塑料诱导的肠道菌群失调导致神经退行性变的机制洞察

Mechanistic insight of neurodegeneration due to micro/nano-plastic-induced gut dysbiosis.

作者信息

Ghosh Arya, Gorain Bapi

机构信息

Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Ranchi, Jharkhand, 835215, India.

出版信息

Arch Toxicol. 2025 Jan;99(1):83-101. doi: 10.1007/s00204-024-03875-3. Epub 2024 Oct 6.

Abstract

Despite offering significant conveniences, plastic materials contribute substantially in developing environmental hazards and pollutants. Plastic trash that has not been adequately managed may eventually break down into fragments caused by human or ecological factors. Arguably, the crucial element for determining the biological toxicities of plastics are micro/nano-forms of plastics (MPs/NPs), which infiltrate the mammalian tissue through different media and routes. Infiltration of MPs/NPs across the intestinal barrier leads to microbial architectural dysfunction, which further modulates the population of gastrointestinal microbes. Thereby, it triggers inflammatory mediators (e.g., IL-1α/β, TNF-α, and IFN-γ) by activating specific receptors located in the gut barrier. Mounting evidence indicates that MPs/NPs disrupt host pathophysiological function through modification of junctional proteins and effector cells. Moreover, the alteration of microbial diversity by MPs/NPs causes the breakdown of the blood-brain barrier and translocation of metabolites (e.g., SCFAs, LPS) through the vagus nerve. Potent penetration affects the neuronal networks, neuronal protein accumulation, acceleration of oxidative stress, and alteration of neurofibrillary tangles, and hinders distinctive communicating pathways. Conclusively, alterations of these neurotoxic factors are possibly responsible for the associated neurodegenerative disorders due to the exposure of MPs/NPs. In this review, the hypothesis on MPs/NPs associated with gut microbial dysbiosis has been interlinked to the distinct neurological impairment through the gut-brain axis.

摘要

尽管塑料材料提供了极大的便利,但它们对环境危害和污染物的产生也有很大的影响。未经妥善管理的塑料垃圾最终可能会因人为或生态因素分解成碎片。可以说,决定塑料生物毒性的关键因素是微塑料/纳米塑料(MPs/NPs),它们通过不同的介质和途径渗透到哺乳动物组织中。MPs/NPs穿过肠道屏障会导致微生物结构功能障碍,进而进一步调节胃肠道微生物的数量。因此,它通过激活位于肠道屏障中的特定受体来触发炎症介质(如IL-1α/β、TNF-α和IFN-γ)。越来越多的证据表明,MPs/NPs通过改变连接蛋白和效应细胞来破坏宿主的病理生理功能。此外,MPs/NPs导致的微生物多样性改变会导致血脑屏障的破坏以及代谢产物(如短链脂肪酸、脂多糖)通过迷走神经的转运。强大的穿透力会影响神经网络、神经元蛋白质积累、氧化应激加速以及神经纤维缠结的改变,并阻碍独特的通讯途径。总之,由于暴露于MPs/NPs,这些神经毒性因素的改变可能是导致相关神经退行性疾病的原因。在这篇综述中,与肠道微生物失调相关的MPs/NPs假说已通过肠-脑轴与明显的神经损伤联系起来。

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