Parkinson's Disease and the Metal-Microbiome-Gut-Brain Axis: A Systems Toxicology Approach.
Parkinson’s disease
ROS
heavy metals
human microbiome
neurotoxicity
systems toxicology
Journal
Antioxidants (Basel, Switzerland)
ISSN: 2076-3921
Titre abrégé: Antioxidants (Basel)
Pays: Switzerland
ID NLM: 101668981
Informations de publication
Date de publication:
28 Dec 2021
28 Dec 2021
Historique:
received:
04
11
2021
revised:
02
12
2021
accepted:
17
12
2021
entrez:
21
1
2022
pubmed:
22
1
2022
medline:
22
1
2022
Statut:
epublish
Résumé
Parkinson's Disease (PD) is a neurodegenerative disease, leading to motor and non-motor complications. Autonomic alterations, including gastrointestinal symptoms, precede motor defects and act as early warning signs. Chronic exposure to dietary, environmental heavy metals impacts the gastrointestinal system and host-associated microbiome, eventually affecting the central nervous system. The correlation between dysbiosis and PD suggests a functional and bidirectional communication between the gut and the brain. The bioaccumulation of metals promotes stress mechanisms by increasing reactive oxygen species, likely altering the bidirectional gut-brain link. To better understand the differing molecular mechanisms underlying PD, integrative modeling approaches are necessary to connect multifactorial perturbations in this heterogeneous disorder. By exploring the effects of gut microbiota modulation on dietary heavy metal exposure in relation to PD onset, the modification of the host-associated microbiome to mitigate neurological stress may be a future treatment option against neurodegeneration through bioremediation. The progressive movement towards a systems toxicology framework for precision medicine can uncover molecular mechanisms underlying PD onset such as metal regulation and microbial community interactions by developing predictive models to better understand PD etiology to identify options for novel treatments and beyond. Several methodologies recently addressed the complexity of this interaction from different perspectives; however, to date, a comprehensive review of these approaches is still lacking. Therefore, our main aim through this manuscript is to fill this gap in the scientific literature by reviewing recently published papers to address the surrounding questions regarding the underlying molecular mechanisms between metals, microbiota, and the gut-brain-axis, as well as the regulation of this system to prevent neurodegeneration.
Identifiants
pubmed: 35052575
pii: antiox11010071
doi: 10.3390/antiox11010071
pmc: PMC8773335
pii:
doi:
Types de publication
Journal Article
Review
Langues
eng
Subventions
Organisme : Precision Medicine in Chronic Inflammation
ID : EXC 2167
Organisme : Research Unit miTarget
ID : FOR5042
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