Gut microenvironmental changes as a potential trigger in Parkinson’s disease through the gut–brain axis
Abstract Parkinson’s disease (PD) is the second most common neurodegenerative disease attributed to the synergistic effects of genetic risk and environmental stimuli. Although PD is characterized by motor dysfunction resulting from intraneuronal alpha-synuclein accumulations, termed Lewy bodies, and...
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| Format: | Article |
| Language: | English |
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BMC
2022-07-01
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| Series: | Journal of Biomedical Science |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12929-022-00839-6 |
| _version_ | 1828778253366591488 |
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| author | Szu-Ju Chen Chin-Hsien Lin |
| author_facet | Szu-Ju Chen Chin-Hsien Lin |
| author_sort | Szu-Ju Chen |
| collection | DOAJ |
| description | Abstract Parkinson’s disease (PD) is the second most common neurodegenerative disease attributed to the synergistic effects of genetic risk and environmental stimuli. Although PD is characterized by motor dysfunction resulting from intraneuronal alpha-synuclein accumulations, termed Lewy bodies, and dopaminergic neuronal degeneration in the substantia nigra, multiple systems are involved in the disease process, resulting in heterogenous clinical presentation and progression. Genetic predisposition to PD regarding aberrant immune responses, abnormal protein aggregation, autophagolysosomal impairment, and mitochondrial dysfunction leads to vulnerable neurons that are sensitive to environmental triggers and, together, result in neuronal degeneration. Neuropathology studies have shown that, at least in some patients, Lewy bodies start from the enteric nervous system and then spread to the central dopaminergic neurons through the gut–brain axis, suggesting the contribution of an altered gut microenvironment in the pathogenesis of PD. A plethora of evidence has revealed different gut microbiomes and gut metabolites in patients with PD compared to unaffected controls. Chronic gut inflammation and impaired intestinal barrier integrity have been observed in human PD patients and mouse models of PD. These observations led to the hypothesis that an altered gut microenvironment is a potential trigger of the PD process in a genetically susceptible host. In this review, we will discuss the complex interplay between genetic factors and gut microenvironmental changes contributing to PD pathogenesis. |
| first_indexed | 2024-12-11T16:38:35Z |
| format | Article |
| id | doaj.art-f559d37e30614fc9b4616395d379fdf2 |
| institution | Directory Open Access Journal |
| issn | 1423-0127 |
| language | English |
| last_indexed | 2024-12-11T16:38:35Z |
| publishDate | 2022-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Biomedical Science |
| spelling | doaj.art-f559d37e30614fc9b4616395d379fdf22022-12-22T00:58:24ZengBMCJournal of Biomedical Science1423-01272022-07-0129111810.1186/s12929-022-00839-6Gut microenvironmental changes as a potential trigger in Parkinson’s disease through the gut–brain axisSzu-Ju Chen0Chin-Hsien Lin1Department of Neurology, National Taiwan University Hospital, College of Medicine, National Taiwan UniversityDepartment of Neurology, National Taiwan University Hospital, College of Medicine, National Taiwan UniversityAbstract Parkinson’s disease (PD) is the second most common neurodegenerative disease attributed to the synergistic effects of genetic risk and environmental stimuli. Although PD is characterized by motor dysfunction resulting from intraneuronal alpha-synuclein accumulations, termed Lewy bodies, and dopaminergic neuronal degeneration in the substantia nigra, multiple systems are involved in the disease process, resulting in heterogenous clinical presentation and progression. Genetic predisposition to PD regarding aberrant immune responses, abnormal protein aggregation, autophagolysosomal impairment, and mitochondrial dysfunction leads to vulnerable neurons that are sensitive to environmental triggers and, together, result in neuronal degeneration. Neuropathology studies have shown that, at least in some patients, Lewy bodies start from the enteric nervous system and then spread to the central dopaminergic neurons through the gut–brain axis, suggesting the contribution of an altered gut microenvironment in the pathogenesis of PD. A plethora of evidence has revealed different gut microbiomes and gut metabolites in patients with PD compared to unaffected controls. Chronic gut inflammation and impaired intestinal barrier integrity have been observed in human PD patients and mouse models of PD. These observations led to the hypothesis that an altered gut microenvironment is a potential trigger of the PD process in a genetically susceptible host. In this review, we will discuss the complex interplay between genetic factors and gut microenvironmental changes contributing to PD pathogenesis.https://doi.org/10.1186/s12929-022-00839-6Parkinson’s diseaseGut microenvironmentGastrointestinal inflammationImpaired intestinal barrierGut microbiotaGut–brain axis |
| spellingShingle | Szu-Ju Chen Chin-Hsien Lin Gut microenvironmental changes as a potential trigger in Parkinson’s disease through the gut–brain axis Journal of Biomedical Science Parkinson’s disease Gut microenvironment Gastrointestinal inflammation Impaired intestinal barrier Gut microbiota Gut–brain axis |
| title | Gut microenvironmental changes as a potential trigger in Parkinson’s disease through the gut–brain axis |
| title_full | Gut microenvironmental changes as a potential trigger in Parkinson’s disease through the gut–brain axis |
| title_fullStr | Gut microenvironmental changes as a potential trigger in Parkinson’s disease through the gut–brain axis |
| title_full_unstemmed | Gut microenvironmental changes as a potential trigger in Parkinson’s disease through the gut–brain axis |
| title_short | Gut microenvironmental changes as a potential trigger in Parkinson’s disease through the gut–brain axis |
| title_sort | gut microenvironmental changes as a potential trigger in parkinson s disease through the gut brain axis |
| topic | Parkinson’s disease Gut microenvironment Gastrointestinal inflammation Impaired intestinal barrier Gut microbiota Gut–brain axis |
| url | https://doi.org/10.1186/s12929-022-00839-6 |
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