Oral ingestion of the environmental toxicant trichloroethylene in rats induces alterations in the gut microbiome: Relevance to idiopathic Parkinson's disease.
Oral ingestion of the environmental toxicant trichloroethylene in rats induces alterations in the gut microbiome: Relevance to idiopathic Parkinson's disease.
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DOI：
10.1016/j.taap.2022.116176
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发表时间：
2022-09-15
影响因子：
3.8
通讯作者：
De Miranda BR
中科院分区：
文献类型：
--
作者：
Ilieva NM;Wallen ZD;De Miranda BR
肠道微生物组内的微生物改变似乎是帕金森病 (PD) 患者的一个共同特征，这为肠-脑轴在帕金森病发展中的作用提供了进一步的证据。作为与环境接触的主要场所，与帕金森病风险相关的环境污染物（例如农药、金属和有机溶剂）对肠道微生物群的改变的因果关系已经出现了一些问题。我们实验室的最新数据表明，摄入工业副产品和环境污染物三氯乙烯 (TCE) 会诱发老年大鼠出现关键的帕金森病病理，包括多巴胺能神经元变性、α-突触核蛋白积累、神经炎症和内溶酶体缺陷。由于 TCE 是饮用水中最常见的有机污染物，我们推测摄入与 PD 相关的神经变性相关的 TCE 可能会改变肠道微生物组，其程度与在 PD 患者中观察到的程度相似。为了评估这一点，我们收集了通过口服强饲法（引起黑质纹状体神经变性的剂量）接受 200 mg/kg TCE 处理 6 周的成年大鼠的粪便样本，并通过全基因组鸟枪测序分析了肠道微生物组。我们的结果显示，肠道微生物的变化反映了在特发性帕金森病患者中观察到的微生物特征，例如产生短链脂肪酸的布劳氏菌丰度减少和产生乳酸的双歧杆菌增多，以及含有先前报道为机会性病原体的菌属（例如梭状芽胞杆菌）的菌属。根据这些实验数据，我们假设接触受污染的饮用水中的三氯乙烯可能会引起肠道微生物组的改变，从而导致慢性疾病风险，包括特发性帕金森病。
Microbial alterations within the gut microbiome appear to be a common feature of individuals with Parkinson’s disease (PD), providing further evidence for the role of the gut-brain axis in PD development. As a major site of contact with the environment, questions have emerged surrounding the cause and effect of alterations to the gut microbiome by environmental contaminants associated with PD risk, such as pesticides, metals, and organic solvents. Recent data from our lab shows that ingestion of the industrial byproduct and environmental pollutant trichloroethylene (TCE) induces key Parkinsonian pathology within aged rats, including the degeneration of dopaminergic neurons, α-synuclein accumulation, neuroinflammation, and endolysosomal deficits. As TCE is the most common organic contaminant within drinking water, we postulated that ingestion of TCE associated with PD-related neurodegeneration may alter the gut microbiome to a similar extent as observed in persons with PD. To assess this, we collected fecal samples from adult rats treated with 200 mg/kg TCE over 6 weeks via oral gavage – the dose that produced nigrostriatal neurodegeneration – and analyzed the gut microbiome via whole genome shotgun sequencing. Our results showed changes in gut microorganisms reflective of the microbial signatures observed in individuals with idiopathic PD, such as decreased abundance of short-chain fatty acid producing Blautia and elevated lactic-acid producing Bifidobacteria, as well as genera who contain species previously reported as opportunistic pathogens such as Clostridium. From these experimental data, we postulate that TCE exposure within contaminated drinking water could induce alterations of the gut microbiome that contributes to chronic disease risk, including idiopathic PD.
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DOI：
10.1002/mds.27105
发表时间：
2018-01
期刊：
Movement disorders : official journal of the Movement Disorder Society
影响因子：
--
作者：
Heintz-Buschart A;Pandey U;Wicke T;Sixel-Döring F;Janzen A;Sittig-Wiegand E;Trenkwalder C;Oertel WH;Mollenhauer B;Wilmes P
通讯作者：
Wilmes P
影响因子：
3.7
作者：
Hasan NA;Young BA;Minard-Smith AT;Saeed K;Li H;Heizer EM;McMillan NJ;Isom R;Abdullah AS;Bornman DM;Faith SA;Choi SY;Dickens ML;Cebula TA;Colwell RR
通讯作者：
Colwell RR
影响因子：
4.3
作者：
Jin, Miao;Li, Jing;Alkasir, Rashad
通讯作者：
Alkasir, Rashad
影响因子：
4.4
作者：
FREEDMAN, DL;GOSSETT, JM
通讯作者：
GOSSETT, JM
影响因子：
5.2
作者：
Engen, Phillip A.;Dodiya, Hemraj B.;Keshavarzian, Ali
通讯作者：
Keshavarzian, Ali