Ketogenic diet protects MPTP‐induced mouse model of Parkinson's disease via altering gut microbiota and metabolites
Abstract The ketogenic diet (KD) is a low‐carbohydrate, high‐fat regime that is protective against neurodegenerative diseases. However, the impact of KD on Parkinson's disease (PD) and its mechanisms remains unclear. 1‐Methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP)‐induced mouse model of PD...
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Wiley
2023-06-01
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| Series: | MedComm |
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| Online Access: | https://doi.org/10.1002/mco2.268 |
| _version_ | 1797802552940560384 |
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| author | Ziying Jiang Xinyu Wang Haoqiang Zhang Jian Yin Peiqing Zhao Qingqing Yin Zhenfu Wang |
| author_facet | Ziying Jiang Xinyu Wang Haoqiang Zhang Jian Yin Peiqing Zhao Qingqing Yin Zhenfu Wang |
| author_sort | Ziying Jiang |
| collection | DOAJ |
| description | Abstract The ketogenic diet (KD) is a low‐carbohydrate, high‐fat regime that is protective against neurodegenerative diseases. However, the impact of KD on Parkinson's disease (PD) and its mechanisms remains unclear. 1‐Methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP)‐induced mouse model of PD was fed with KD for 8 weeks. Motor function and dopaminergic neurons were evaluated. Inflammation in the brain, plasma, and colon tissue were also measured. Fecal samples were assessed by 16S rDNA gene sequencing and untargeted metabolomics. We found that KD protected motor dysfunction, dopaminergic neuron loss, and inflammation in an MPTP mouse model of PD. 16S rDNA sequencing revealed that MPTP administration significantly increased Citrobacter, Desulfovibrio, and Ruminococcus, and decreased Dubosiella, whereas KD treatment reversed the dysbiosis. Meanwhile, KD regulated the MPTP‐induced histamine, N‐acetylputrescine, d‐aspartic acid, and other metabolites. Fecal microbiota transplantation using feces from the KD‐treated mice attenuated the motor function impairment and dopaminergic neuron loss in antibiotic‐pretreated PD mice. Our current study demonstrates that KD played a neuroprotective role in the MPTP mouse model of PD through the diet–gut microbiota–brain axis, which may involve inflammation in the brain and colon. However, future research is warranted to explore the explicit anti‐inflammatory mechanisms of the gut–brain axis in PD models fed with KD. |
| first_indexed | 2024-03-13T05:07:24Z |
| format | Article |
| id | doaj.art-ed9405fc4fbe4c57a71ebf8ecfc58b4c |
| institution | Directory Open Access Journal |
| issn | 2688-2663 |
| language | English |
| last_indexed | 2024-03-13T05:07:24Z |
| publishDate | 2023-06-01 |
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| record_format | Article |
| series | MedComm |
| spelling | doaj.art-ed9405fc4fbe4c57a71ebf8ecfc58b4c2023-06-16T09:40:37ZengWileyMedComm2688-26632023-06-0143n/an/a10.1002/mco2.268Ketogenic diet protects MPTP‐induced mouse model of Parkinson's disease via altering gut microbiota and metabolitesZiying Jiang0Xinyu Wang1Haoqiang Zhang2Jian Yin3Peiqing Zhao4Qingqing Yin5Zhenfu Wang6Department of Geriatric Neurology The Second Medical Center & National Clinical Research Center for Geriatric Disease Chinese PLA General Hospital Beijing ChinaDepartment of Geriatric Neurology Shandong Provincial Hospital Affiliated to Shandong First Medical University Jinan Shandong ChinaDepartment of Endocrinology The First Affiliated Hospital of USTC Division of Life Sciences and Medicine University of Science and Technology of China Hefei Anhui ChinaDepartment of Bio‐Medical Diagnostics Suzhou Institute of Biomedical Engineering and Technology Chinese Academy of Sciences Suzhou Jiangsu ChinaDepartment of Translational Medical Center Zibo Central Hospital Affiliated to Binzhou Medical University Zibo Shandong ChinaDepartment of Geriatric Neurology Shandong Provincial Hospital Affiliated to Shandong First Medical University Jinan Shandong ChinaDepartment of Geriatric Neurology The Second Medical Center & National Clinical Research Center for Geriatric Disease Chinese PLA General Hospital Beijing ChinaAbstract The ketogenic diet (KD) is a low‐carbohydrate, high‐fat regime that is protective against neurodegenerative diseases. However, the impact of KD on Parkinson's disease (PD) and its mechanisms remains unclear. 1‐Methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP)‐induced mouse model of PD was fed with KD for 8 weeks. Motor function and dopaminergic neurons were evaluated. Inflammation in the brain, plasma, and colon tissue were also measured. Fecal samples were assessed by 16S rDNA gene sequencing and untargeted metabolomics. We found that KD protected motor dysfunction, dopaminergic neuron loss, and inflammation in an MPTP mouse model of PD. 16S rDNA sequencing revealed that MPTP administration significantly increased Citrobacter, Desulfovibrio, and Ruminococcus, and decreased Dubosiella, whereas KD treatment reversed the dysbiosis. Meanwhile, KD regulated the MPTP‐induced histamine, N‐acetylputrescine, d‐aspartic acid, and other metabolites. Fecal microbiota transplantation using feces from the KD‐treated mice attenuated the motor function impairment and dopaminergic neuron loss in antibiotic‐pretreated PD mice. Our current study demonstrates that KD played a neuroprotective role in the MPTP mouse model of PD through the diet–gut microbiota–brain axis, which may involve inflammation in the brain and colon. However, future research is warranted to explore the explicit anti‐inflammatory mechanisms of the gut–brain axis in PD models fed with KD.https://doi.org/10.1002/mco2.268gut microbiotainflammationketogenic dietmetabolitesParkinson's disease |
| spellingShingle | Ziying Jiang Xinyu Wang Haoqiang Zhang Jian Yin Peiqing Zhao Qingqing Yin Zhenfu Wang Ketogenic diet protects MPTP‐induced mouse model of Parkinson's disease via altering gut microbiota and metabolites MedComm gut microbiota inflammation ketogenic diet metabolites Parkinson's disease |
| title | Ketogenic diet protects MPTP‐induced mouse model of Parkinson's disease via altering gut microbiota and metabolites |
| title_full | Ketogenic diet protects MPTP‐induced mouse model of Parkinson's disease via altering gut microbiota and metabolites |
| title_fullStr | Ketogenic diet protects MPTP‐induced mouse model of Parkinson's disease via altering gut microbiota and metabolites |
| title_full_unstemmed | Ketogenic diet protects MPTP‐induced mouse model of Parkinson's disease via altering gut microbiota and metabolites |
| title_short | Ketogenic diet protects MPTP‐induced mouse model of Parkinson's disease via altering gut microbiota and metabolites |
| title_sort | ketogenic diet protects mptp induced mouse model of parkinson s disease via altering gut microbiota and metabolites |
| topic | gut microbiota inflammation ketogenic diet metabolites Parkinson's disease |
| url | https://doi.org/10.1002/mco2.268 |
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