N-acetyl-L-leucine protects MPTP-treated Parkinson’s disease mouse models by suppressing Desulfobacterota via the gut-brain axis
Parkinson's disease (PD) is the second most common neurodegenerative disease, and communication between the gut and brain (the gut-brain axis) has been found to be essential in behavior and cognitive function. However, the exact mechanisms underlying microbiota dysbiosis in PD progression have...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-10-01
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| Series: | Brain Research Bulletin |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0361923023001545 |
| _version_ | 1827810114817490944 |
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| author | Zhifeng Xu Changlin Lian Lixin Pan Wenjie Lai Fen Zhang Lingmei Peng Sijie Zhou Guanghua Zhao Xuezhu Yang Guohua Zhang Zefeng Tan Yukai Wang |
| author_facet | Zhifeng Xu Changlin Lian Lixin Pan Wenjie Lai Fen Zhang Lingmei Peng Sijie Zhou Guanghua Zhao Xuezhu Yang Guohua Zhang Zefeng Tan Yukai Wang |
| author_sort | Zhifeng Xu |
| collection | DOAJ |
| description | Parkinson's disease (PD) is the second most common neurodegenerative disease, and communication between the gut and brain (the gut-brain axis) has been found to be essential in behavior and cognitive function. However, the exact mechanisms underlying microbiota dysbiosis in PD progression have not yet been elucidated. Our study aimed to investigate the correlation between gut microbiota disturbances and feces metabolic disorders in PD. We used 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to induce PD models and observed mice's motor symptoms, dopaminergic (DA) neuron death, and gastrointestinal dysfunction. To identify alterations in microbiota and metabolome, feces were collected from mice and analyzed using 16 S ribosomal RNA sequencing feces metabolomics. Pearson analysis was utilized to investigate correlations between the abundances of gut microbiota components and the levels of gut microbiota metabolites, displaying their interaction networks. Our findings revealed a significant increase in Desulfobacterota in the PD mouse model and 151 differentially expressed fecal metabolites between PD and vehicle mice. Moreover, Pearson correlation analysis suggested that the protective factor N-acetyl-L-leucine (NALL) may be associated with neuroinflammation in the striatum and substantia nigra, which also had a negative relationship with the concentration of Desulfobacterota. Additionally, we found that oral administration of NALL alleviated MPTP-induced Motor Impairments and DA neuronal deficits. All in all, we concluded that the decrease of NALL might lead to a significant increase of Desulfobacterota in the MPTP model mouse and subsequently result in the damage of DA neurons via the gut-brain aix pathway. |
| first_indexed | 2024-03-11T22:49:12Z |
| format | Article |
| id | doaj.art-d87a82c1fa674798beb3194ba28a8299 |
| institution | Directory Open Access Journal |
| issn | 1873-2747 |
| language | English |
| last_indexed | 2024-03-11T22:49:12Z |
| publishDate | 2023-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Brain Research Bulletin |
| spelling | doaj.art-d87a82c1fa674798beb3194ba28a82992023-09-22T04:37:55ZengElsevierBrain Research Bulletin1873-27472023-10-01202110729N-acetyl-L-leucine protects MPTP-treated Parkinson’s disease mouse models by suppressing Desulfobacterota via the gut-brain axisZhifeng Xu0Changlin Lian1Lixin Pan2Wenjie Lai3Fen Zhang4Lingmei Peng5Sijie Zhou6Guanghua Zhao7Xuezhu Yang8Guohua Zhang9Zefeng Tan10Yukai Wang11Department of Neurology, The First People's Hospital of Foshan, Foshan, ChinaDepartment of Neurology, The First People's Hospital of Foshan, Foshan, ChinaDepartment of Neurology, The First People's Hospital of Foshan, Foshan, ChinaDepartment of Neurology, The First People's Hospital of Foshan, Foshan, China; Department of Neurology, The Sixth Affiliated Hospital, School of Medicine, South China University of Technology, ChinaDepartment of Neurology, The First People's Hospital of Foshan, Foshan, ChinaDepartment of Neurology, The First People's Hospital of Foshan, Foshan, ChinaDepartment of Cerebrovascular Surgery, The First People's Hospital of Foshan, Foshan, ChinaDepartment of Laboratory Medicine, The First People's Hospital of Foshan, Foshan, ChinaDepartment of Gastroenterology, The First People's Hospital of Foshan, Foshan, ChinaDepartment of Neurology, The First People's Hospital of Foshan, Foshan, China; Department of Neurology, The Sixth Affiliated Hospital, School of Medicine, South China University of Technology, China; Corresponding author at: Department of Neurology, The First People's Hospital of Foshan, Foshan, China.Department of Neurology, The First People's Hospital of Foshan, Foshan, China; Corresponding authors.Department of Neurology, The First People's Hospital of Foshan, Foshan, China; Corresponding authors.Parkinson's disease (PD) is the second most common neurodegenerative disease, and communication between the gut and brain (the gut-brain axis) has been found to be essential in behavior and cognitive function. However, the exact mechanisms underlying microbiota dysbiosis in PD progression have not yet been elucidated. Our study aimed to investigate the correlation between gut microbiota disturbances and feces metabolic disorders in PD. We used 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to induce PD models and observed mice's motor symptoms, dopaminergic (DA) neuron death, and gastrointestinal dysfunction. To identify alterations in microbiota and metabolome, feces were collected from mice and analyzed using 16 S ribosomal RNA sequencing feces metabolomics. Pearson analysis was utilized to investigate correlations between the abundances of gut microbiota components and the levels of gut microbiota metabolites, displaying their interaction networks. Our findings revealed a significant increase in Desulfobacterota in the PD mouse model and 151 differentially expressed fecal metabolites between PD and vehicle mice. Moreover, Pearson correlation analysis suggested that the protective factor N-acetyl-L-leucine (NALL) may be associated with neuroinflammation in the striatum and substantia nigra, which also had a negative relationship with the concentration of Desulfobacterota. Additionally, we found that oral administration of NALL alleviated MPTP-induced Motor Impairments and DA neuronal deficits. All in all, we concluded that the decrease of NALL might lead to a significant increase of Desulfobacterota in the MPTP model mouse and subsequently result in the damage of DA neurons via the gut-brain aix pathway.http://www.sciencedirect.com/science/article/pii/S0361923023001545DesulfobacterotaMicrobiota dysbiosisGut-brain axisN-acetyl-L-leucineParkinson’s disease |
| spellingShingle | Zhifeng Xu Changlin Lian Lixin Pan Wenjie Lai Fen Zhang Lingmei Peng Sijie Zhou Guanghua Zhao Xuezhu Yang Guohua Zhang Zefeng Tan Yukai Wang N-acetyl-L-leucine protects MPTP-treated Parkinson’s disease mouse models by suppressing Desulfobacterota via the gut-brain axis Brain Research Bulletin Desulfobacterota Microbiota dysbiosis Gut-brain axis N-acetyl-L-leucine Parkinson’s disease |
| title | N-acetyl-L-leucine protects MPTP-treated Parkinson’s disease mouse models by suppressing Desulfobacterota via the gut-brain axis |
| title_full | N-acetyl-L-leucine protects MPTP-treated Parkinson’s disease mouse models by suppressing Desulfobacterota via the gut-brain axis |
| title_fullStr | N-acetyl-L-leucine protects MPTP-treated Parkinson’s disease mouse models by suppressing Desulfobacterota via the gut-brain axis |
| title_full_unstemmed | N-acetyl-L-leucine protects MPTP-treated Parkinson’s disease mouse models by suppressing Desulfobacterota via the gut-brain axis |
| title_short | N-acetyl-L-leucine protects MPTP-treated Parkinson’s disease mouse models by suppressing Desulfobacterota via the gut-brain axis |
| title_sort | n acetyl l leucine protects mptp treated parkinson s disease mouse models by suppressing desulfobacterota via the gut brain axis |
| topic | Desulfobacterota Microbiota dysbiosis Gut-brain axis N-acetyl-L-leucine Parkinson’s disease |
| url | http://www.sciencedirect.com/science/article/pii/S0361923023001545 |
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