4.6 Article

Oral ingestion of the environmental toxicant trichloroethylene in rats induces alterations in the gut microbiome: Relevance to idiopathic Parkinson's disease

期刊

TOXICOLOGY AND APPLIED PHARMACOLOGY
卷 451, 期 -, 页码 -

出版社

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.taap.2022.116176

关键词

Microbiome; Trichloroethylene; Parkinson's disease

资金

  1. National Institutes of Environmental Health Sciences [R00ES029986]
  2. Parkinson Association of Alabama (BRD)

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Microbial alterations within the gut microbiome are common in individuals with Parkinson's disease, supporting the involvement of the gut-brain axis in PD development. Exposure to environmental contaminants like trichloroethylene (TCE) can induce similar changes in the gut microbiome as observed in PD. The study suggests that exposure to TCE in contaminated drinking water may contribute to the risk of chronic diseases, including idiopathic PD.
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, alpha-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 pre-viously 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 con-tributes to chronic disease risk, including idiopathic PD.

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