Cited by 50Parkinson's Disease Mechanisms and TreatmentsGut microbiota and healthDiet and metabolism studies

Ketogenic diet protects MPTP‐induced mouse model of Parkinson's disease via altering gut microbiota and metabolites

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Jiang, Ziying, Wang, Xinyu, Zhang, Haoqiang, Yin, Jian, Zhao, Peiqing, Yin, Qingqing, Wang, Zhenfu·2023·MedComm

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.

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  • Amelioration of gut dysbiosis in MPTP-induced mice via FMT, dietary intervention, and probiotic administration alleviates neuroinflammation and dopaminergic neuron loss.

    “The amelioration of gut dysbiosis in MPTP-induced mice via FMT, dietary intervention, and probiotic administration has been shown to alleviate neuroinflammation and dopaminergic neuron loss.”
  • The alleviation of neuroinflammation and dopaminergic neuron loss by gut dysbiosis amelioration is attributed to reduction of glial activation and restoration of metabolite and neurotransmitter abnormalities.

    “These effects are attributed to the reduction of glial activation, as well as the restoration of metabolite and neurotransmitter abnormalities.217,259–261”

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Authors
Jiang, Z., Wang, X., Zhang, H., Yin, J., Zhao, P., Yin, Q., & Wang, Z.
Affiliations
  • Chinese PLA General Hospital (CN)
  • Shandong Provincial Hospital (CN)
  • University of Science and Technology of China (CN)
  • Chinese Academy of Sciences (CN)
  • Binzhou Medical University (CN)
Corresponding author
  • Yin, Qingqing
  • Wang, Zhenfu
Venue
MedComm
Publisher
Wiley
Published
2023-05-16
Volume
4
Issue
3
Pages
e268-e268
ISSN
2688-2663 (ISSN-L)
OpenAlex
W4376954864
Cited by
50
References
83
Citations by year
2026: 14 · 2025: 18 · 2024: 14 · 2023: 4
FWCI
8.42
Type
journal article
Language
en
Open access
Locations
  • MedComm (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
National Natural Science Foundation of China (82000771)
Topics
  • Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Health Sciences › Medicine › Physiology › Diet and metabolism studies
Keywords
ketogenic diet, Parkinson's disease, MPTP mouse model, gut microbiota, gut-brain axis, neuroprotection, dopaminergic neuron loss, motor impairment, gut dysbiosis, fecal microbiota transplantation, histamine, N-acetylputrescine, D-aspartic acid, metabolomics

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