Gut–brain axis and environmental factors in Parkinson’s disease: bidirectional link between disease onset and progression
Parkinson’s disease has long been considered a disorder that primarily affects the brain, as it is defined by the dopaminergic neurodegeneration in the substantia nigra and the brain accumulation of Lewy bodies containing α-synuclein protein. In recent decades, however, accumulating research has rev...
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| Format: | Article |
| Language: | English |
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Wolters Kluwer Medknow Publications
2025-12-01
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| Series: | Neural Regeneration Research |
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| Online Access: | https://journals.lww.com/10.4103/NRR.NRR-D-24-00994 |
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| author | Soo Jung Park Kyung Won Kim Eun Jeong Lee |
| author_facet | Soo Jung Park Kyung Won Kim Eun Jeong Lee |
| author_sort | Soo Jung Park |
| collection | DOAJ |
| description | Parkinson’s disease has long been considered a disorder that primarily affects the brain, as it is defined by the dopaminergic neurodegeneration in the substantia nigra and the brain accumulation of Lewy bodies containing α-synuclein protein. In recent decades, however, accumulating research has revealed that Parkinson’s disease also involves the gut and uncovered an intimate and important bidirectional link between the brain and the gut, called the “gut–brain axis.” Numerous clinical studies demonstrate that gut dysfunction frequently precedes motor symptoms in Parkinson’s disease patients, with findings including impaired intestinal permeability, heightened inflammation, and distinct gut microbiome profiles and metabolites. Furthermore, α-synuclein deposition has been consistently observed in the gut of Parkinson’s disease patients, suggesting a potential role in disease initiation. Importantly, individuals with vagotomy have a reduced Parkinson’s disease risk. From these observations, researchers have hypothesized that α-synuclein accumulation may initiate in the gut and subsequently propagate to the central dopaminergic neurons through the gut–brain axis, leading to Parkinson’s disease. This review comprehensively examines the gut’s involvement in Parkinson’s disease, focusing on the concept of a gut-origin for the disease. We also examine the interplay between altered gut-related factors and the accumulation of pathological α-synuclein in the gut of Parkinson’s disease patients. Given the accessibility of the gut to both dietary and pharmacological interventions, targeting gut-localized α-synuclein represents a promising avenue for developing effective Parkinson’s disease therapies. |
| format | Article |
| id | doaj-art-72d248716ea24329bc8a8d7123ef6cdf |
| institution | Kabale University |
| issn | 1673-5374 1876-7958 |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Wolters Kluwer Medknow Publications |
| record_format | Article |
| series | Neural Regeneration Research |
| spelling | doaj-art-72d248716ea24329bc8a8d7123ef6cdf2025-02-06T09:58:38ZengWolters Kluwer Medknow PublicationsNeural Regeneration Research1673-53741876-79582025-12-0120123416342910.4103/NRR.NRR-D-24-00994Gut–brain axis and environmental factors in Parkinson’s disease: bidirectional link between disease onset and progressionSoo Jung ParkKyung Won KimEun Jeong LeeParkinson’s disease has long been considered a disorder that primarily affects the brain, as it is defined by the dopaminergic neurodegeneration in the substantia nigra and the brain accumulation of Lewy bodies containing α-synuclein protein. In recent decades, however, accumulating research has revealed that Parkinson’s disease also involves the gut and uncovered an intimate and important bidirectional link between the brain and the gut, called the “gut–brain axis.” Numerous clinical studies demonstrate that gut dysfunction frequently precedes motor symptoms in Parkinson’s disease patients, with findings including impaired intestinal permeability, heightened inflammation, and distinct gut microbiome profiles and metabolites. Furthermore, α-synuclein deposition has been consistently observed in the gut of Parkinson’s disease patients, suggesting a potential role in disease initiation. Importantly, individuals with vagotomy have a reduced Parkinson’s disease risk. From these observations, researchers have hypothesized that α-synuclein accumulation may initiate in the gut and subsequently propagate to the central dopaminergic neurons through the gut–brain axis, leading to Parkinson’s disease. This review comprehensively examines the gut’s involvement in Parkinson’s disease, focusing on the concept of a gut-origin for the disease. We also examine the interplay between altered gut-related factors and the accumulation of pathological α-synuclein in the gut of Parkinson’s disease patients. Given the accessibility of the gut to both dietary and pharmacological interventions, targeting gut-localized α-synuclein represents a promising avenue for developing effective Parkinson’s disease therapies.https://journals.lww.com/10.4103/NRR.NRR-D-24-00994gut inflammationgut microbiomegut–brain axismicro/nano-plasticsparkinson’s diseaseα-synuclein |
| spellingShingle | Soo Jung Park Kyung Won Kim Eun Jeong Lee Gut–brain axis and environmental factors in Parkinson’s disease: bidirectional link between disease onset and progression Neural Regeneration Research gut inflammation gut microbiome gut–brain axis micro/nano-plastics parkinson’s disease α-synuclein |
| title | Gut–brain axis and environmental factors in Parkinson’s disease: bidirectional link between disease onset and progression |
| title_full | Gut–brain axis and environmental factors in Parkinson’s disease: bidirectional link between disease onset and progression |
| title_fullStr | Gut–brain axis and environmental factors in Parkinson’s disease: bidirectional link between disease onset and progression |
| title_full_unstemmed | Gut–brain axis and environmental factors in Parkinson’s disease: bidirectional link between disease onset and progression |
| title_short | Gut–brain axis and environmental factors in Parkinson’s disease: bidirectional link between disease onset and progression |
| title_sort | gut brain axis and environmental factors in parkinson s disease bidirectional link between disease onset and progression |
| topic | gut inflammation gut microbiome gut–brain axis micro/nano-plastics parkinson’s disease α-synuclein |
| url | https://journals.lww.com/10.4103/NRR.NRR-D-24-00994 |
| work_keys_str_mv | AT soojungpark gutbrainaxisandenvironmentalfactorsinparkinsonsdiseasebidirectionallinkbetweendiseaseonsetandprogression AT kyungwonkim gutbrainaxisandenvironmentalfactorsinparkinsonsdiseasebidirectionallinkbetweendiseaseonsetandprogression AT eunjeonglee gutbrainaxisandenvironmentalfactorsinparkinsonsdiseasebidirectionallinkbetweendiseaseonsetandprogression |