Enrichment of gut-derived metabolites in a Parkinson’s disease subtype with REM sleep behavior disorder
Abstract Recent reports indicate that Parkinson’s disease (PD)-like changes in gut microbial signatures develop in idiopathic REM sleep behavior disorder (iRBD), a prodrome of α-synucleinopathies. However, <50% of PD cases exhibit RBD at onset, underscoring PD’s heterogeneity. Using untargeted me...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-07-01
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| Series: | npj Parkinson's Disease |
| Online Access: | https://doi.org/10.1038/s41531-025-01040-w |
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| author | Sunjae Lee Jihyun Kim Jae Woo Baek Ki-Young Jung Yunjong Lee Ara Koh Han-Joon Kim |
| author_facet | Sunjae Lee Jihyun Kim Jae Woo Baek Ki-Young Jung Yunjong Lee Ara Koh Han-Joon Kim |
| author_sort | Sunjae Lee |
| collection | DOAJ |
| description | Abstract Recent reports indicate that Parkinson’s disease (PD)-like changes in gut microbial signatures develop in idiopathic REM sleep behavior disorder (iRBD), a prodrome of α-synucleinopathies. However, <50% of PD cases exhibit RBD at onset, underscoring PD’s heterogeneity. Using untargeted metabolomics, plasma samples from PD patients with and without RBD, iRBD subjects, and healthy controls were analyzed to characterize the metabolic differences in PD patients with and without RBD. Metabolomic analysis revealed the enrichment of gut microbial-origin metabolites, such as secondary bile acids and p-cresol sulfate, in PD patients with RBD, while metabolites linked to neuropsychiatric diseases were elevated in PD patients without RBD. Additionally, our prediction that p-cresol sulfate, enriched in the RBD groups with a gut microbial origin, crosses the blood-brain barrier, suggests a potential mechanistic link between gut microbial dysbiosis, iRBD, and PD with RBD. Our study elucidates the heterogeneous nature of PD subtypes. |
| format | Article |
| id | doaj-art-5ce4dc4e4e654befaaa88bcd9ee9cd6f |
| institution | DOAJ |
| issn | 2373-8057 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Parkinson's Disease |
| spelling | doaj-art-5ce4dc4e4e654befaaa88bcd9ee9cd6f2025-08-20T03:03:29ZengNature Portfolionpj Parkinson's Disease2373-80572025-07-011111910.1038/s41531-025-01040-wEnrichment of gut-derived metabolites in a Parkinson’s disease subtype with REM sleep behavior disorderSunjae Lee0Jihyun Kim1Jae Woo Baek2Ki-Young Jung3Yunjong Lee4Ara Koh5Han-Joon Kim6Department of Life Sciences, Gwangju Institute of Science and TechnologyDepartment of Life Sciences, Pohang University of Science and TechnologyDepartment of Life Sciences, Gwangju Institute of Science and TechnologyDepartment of Neurology, Seoul National University Hospital, College of Medicine, Seoul National UniversityDepartment of Pharmacology, Sungkyunkwan University School of MedicineDepartment of Life Sciences, Pohang University of Science and TechnologyDepartment of Neurology, Seoul National University Hospital, College of Medicine, Seoul National UniversityAbstract Recent reports indicate that Parkinson’s disease (PD)-like changes in gut microbial signatures develop in idiopathic REM sleep behavior disorder (iRBD), a prodrome of α-synucleinopathies. However, <50% of PD cases exhibit RBD at onset, underscoring PD’s heterogeneity. Using untargeted metabolomics, plasma samples from PD patients with and without RBD, iRBD subjects, and healthy controls were analyzed to characterize the metabolic differences in PD patients with and without RBD. Metabolomic analysis revealed the enrichment of gut microbial-origin metabolites, such as secondary bile acids and p-cresol sulfate, in PD patients with RBD, while metabolites linked to neuropsychiatric diseases were elevated in PD patients without RBD. Additionally, our prediction that p-cresol sulfate, enriched in the RBD groups with a gut microbial origin, crosses the blood-brain barrier, suggests a potential mechanistic link between gut microbial dysbiosis, iRBD, and PD with RBD. Our study elucidates the heterogeneous nature of PD subtypes.https://doi.org/10.1038/s41531-025-01040-w |
| spellingShingle | Sunjae Lee Jihyun Kim Jae Woo Baek Ki-Young Jung Yunjong Lee Ara Koh Han-Joon Kim Enrichment of gut-derived metabolites in a Parkinson’s disease subtype with REM sleep behavior disorder npj Parkinson's Disease |
| title | Enrichment of gut-derived metabolites in a Parkinson’s disease subtype with REM sleep behavior disorder |
| title_full | Enrichment of gut-derived metabolites in a Parkinson’s disease subtype with REM sleep behavior disorder |
| title_fullStr | Enrichment of gut-derived metabolites in a Parkinson’s disease subtype with REM sleep behavior disorder |
| title_full_unstemmed | Enrichment of gut-derived metabolites in a Parkinson’s disease subtype with REM sleep behavior disorder |
| title_short | Enrichment of gut-derived metabolites in a Parkinson’s disease subtype with REM sleep behavior disorder |
| title_sort | enrichment of gut derived metabolites in a parkinson s disease subtype with rem sleep behavior disorder |
| url | https://doi.org/10.1038/s41531-025-01040-w |
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