Fecal Microbiota Transplantation Exerts a Protective Role in MPTP-Induced Parkinson’s Disease via the TLR4/PI3K/AKT/NF-κB Pathway Stimulated by α-Synuclein
Abstract
Gut microbiota is closely related to the Parkinson's disease (PD) pathogenesis. Additionally, aggregation of α-synuclein (α-syn) is central to PD pathogenesis. Here we identified the further mechanisms of gut microbiota in PD. A mouse model with PD was established via injection of MPTP. Normal or MPTP-induced PD like animals were treated with FMT from healthy normal mice. Pole test and traction test were performed to examine the effects of FMT on motor function of PD mice. Fecal SCFAs were assessed by gas chromatography-mass spectrometry. The α-syn level in the substantia nigra pars compacta (SN) of mice was measured using western blot. Dopaminergic neurons and microglial activation in the SN were analyzed by immunohistochemistry (IHC) and immunofluorescence (IF) staining. FMT alleviated physical impairment, decreased fecal SCFAs in a mouse model of PD. Additionally, FMT decreased the expression of α-syn, as well as inhibited the activation of microglia in the SN, and blocked the TLR4/PI3K/AKT/NF-κB signaling in the SN and striatum. FMT could protect mice against PD via suppressing α-syn expression and inactivating the TLR4/PI3K/AKT/NF-κB signaling.
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Reduction of SCFAs in MPTP-induced mice yields beneficial effects, including alleviation of motor dysfunction and microglial and astrocytic activation in the SN.
“Conversely, the reduction of SCFAs in MPTP-induced mice yielded beneficial effects, including alleviation of motor dysfunction, microglial and astrocytic activation in the SN.217,333”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [333]
The beneficial effect of FMT on neuroinflammation is ascribed to GM modulating microglia and astrocyte activation in SN by regulating the TLR4/NF-κB pathway and reducing expression of GSK3β, iNOS and IL-1β.
“This beneficial effect should be ascribed to the ability of GM to modulate microglia and astrocyte activation in SN by regulating the TLR4/NF-κB pro-inflammatory pathway and reducing the expression of GSK3β, iNOS and IL-1β, which are implicated in PD pathogenesis and progression [469,470,471,472,478,479,480].”
From The Interplay between Gut Microbiota and Parkinson’s Disease: Implications on Diagnosis and Treatment (2022) · cites this paper as [471]
FMT contrasts cognitive damage by decreasing α-synuclein expression and restoring optimal levels of striatal dopamine and serotonin, supporting neuroprotection.
“At the brain level, FMT contrasts cognitive damage by decreasing α-synuclein expression and restoring the optimal levels of the striatal neurotransmitters dopamine and serotonin, thus supporting neuroprotection [469,471,473].”
From The Interplay between Gut Microbiota and Parkinson’s Disease: Implications on Diagnosis and Treatment (2022) · cites this paper as [471]
Consistent preclinical studies and a handful of human case reports have shown that FMT might reduce motor and non-motor symptoms, as well as constipation, in PD at least in the short term.
“Concerning PD, consistent preclinical studies and a handful of human case reports have shown that FMT might be exploited to reduce motor and non-motor symptoms, as well as constipation, at least in the short term [40,465,469,470,471,472,473,474,475,476,477] (Table 4).”
From The Interplay between Gut Microbiota and Parkinson’s Disease: Implications on Diagnosis and Treatment (2022) · cites this paper as [471]
Decreased neuroinflammation following FMT has been reported by numerous preclinical studies.
“Notably, decreased neuroinflammation following FMT has been reported by numerous preclinical studies [469,470,471,472].”
From The Interplay between Gut Microbiota and Parkinson’s Disease: Implications on Diagnosis and Treatment (2022) · cites this paper as [471]
Fecal matter transplantation from healthy mice to PD recipient mice improved physical performance, ameliorated motor symptoms and reduced dysbiosis in several independent studies.
“Conversely, fecal matter transplantation from healthy mice to PD recipient mice improved physical performance, ameliorated motor symptoms and reduced dysbiosis in several independent studies [469,470,471,472].”
From The Interplay between Gut Microbiota and Parkinson’s Disease: Implications on Diagnosis and Treatment (2022) · cites this paper as [471]
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- Authors
- Zhong, Z., Chen, W., Gao, H., Che, N., Xu, M., Yang, L., Zhang, Y., & Ye, M.
- Affiliations
- Nanjing Medical University (CN)
- Corresponding author
- Ye, Min
- Venue
- Neurochemical Research
- Published
- 2021-08-04
- Volume
- 46
- Issue
- 11
- Pages
- 3050-3058
- ISSN
- 0364-3190 (ISSN-L)
- 1573-6903
- OpenAlex
- W3192603972
- Cited by
- 66
- References
- 47
- Citations by year
- 2026: 10 · 2025: 12 · 2024: 18 · 2023: 17 · 2022: 9
- FWCI
- 5.26
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neurochemical Research (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Keywords
- fecal microbiota transplantation, Parkinson's disease, MPTP-induced neurotoxicity, alpha-synuclein, gut microbiota, short-chain fatty acids, microglial activation, substantia nigra pars compacta, dopaminergic neurons, motor function, gut-brain axis
- MeSH terms
- Neuroprotection, Fecal Microbiota Transplantation, Animals, Male, Mice, Inbred C57BL, NF-kappa B, Phosphatidylinositol 3-Kinases, Parkinsonian Disorders, Proto-Oncogene Proteins c-akt, Toll-Like Receptor 4, Mice, alpha-Synuclein
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