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Probiotic Clostridium butyricum ameliorated motor deficits in a mouse model of Parkinson’s disease via gut microbiota-GLP-1 pathway
Abstract
A connection between gut microbiota and Parkinson's disease (PD) indicates that dysbiosis of the gut microbiota might represent a risk factor for PD. Microbiota-targeted interventions, including probiotic Clostridium butyricum (Cb), have been recently shown to have favorable effects in PD by regulating microbiota-gut-brain axis. However, the potential beneficial roles and its mechanisms of Cb on PD were still unknown. Male C57BL/6 mice were subjected to a PD model-induced by 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) and were treated intragastrically with Cb for 4 weeks. The motor functions were assessed by a series of behavioral tests including pole test, beam walking teat, forced swimming test and open field test. The dopaminergic neuron loss, synaptic plasticity and microglia activation, as well as the levels of colonic glucagon-like peptide-1 (GLP-1), colonic G protein-coupled receptors GPR41/43 and cerebral GLP-1 receptors were assessed. Gut microbial composition was assessed by 16S rRNA sequencing analysis. Our results showed that oral administration of Cb could improve motor deficits, dopaminergic neuron loss, synaptic dysfunction and microglia activation in the MPTP-induced mice. Meanwhile, Cb treatment could reverse the dysbiosis of gut microbiota and the decreased levels of colonic GLP-1, colonic GPR41/43 and cerebral GLP-1 receptor in the MPTP-induced mice. These findings indicated that the neuroprotective mechanism of Cb on PD might be related to the improvement of abnormal gut microbiota-gut-brain axis.
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In the citing paper
“Notably, the administration of probiotic Clostridium butyricum triggers the activation of colonic GPR41/43, resulting in the inhibition of microglial activation and mitigation of PD-related pathologies in MPTP-treated mice.316”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [316]
In the citing paper
“probiotics and prebiotics are capable of stimulating GLP-1 secretion and upregulating the expression of GLP-1R in the brain.”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [316]
In the citing paper
“probiotic C. butyricum restores colonic GLP-1 levels and upregulates GLP-1R expression in the brains of MPTP-induced mice, accompanied by reduced microglial activation and PD pathologies.”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [316]
In the citing paper
“According to our research, MPTP intervention drastically changed the intestinal microbiota of PD mice (Figure 5), increasing Bacteroides, Escherichia-Shigella, and Dubosiella, and decreasing Akkermansia (Figure 5), which is consistent with the findings of previous studies [47,66,67].”
From Neuroprotective Effects of Bifidobacterium breve CCFM1067 in MPTP-Induced Mouse Models of Parkinson’s Disease (2022) · cites this paper as [67]
In the citing paper
“To create the MPTP mouse model, we applied a technique that was previously reported [25,26].”
From Neuroprotective Effects of Sodium Butyrate by Restoring Gut Microbiota and Inhibiting TLR4 Signaling in Mice with MPTP-Induced Parkinson’s Disease (2023) · cites this paper as [26]
In the citing paper
“Sun and colleagues [440] suggested that neuroprotective effects of Clostridium butyricum in mice with induced Parkinson's disease seem to be due to amelioration of the abnormal gut-brain axis.”
From The Role of Microbiota-Gut-Brain Axis in Neuropsychiatric and Neurological Disorders (2021) · cites this paper as [440]
In the citing paper
“The authors demonstrated that oral administration of the above-mentioned strain improved gut dysbiosis, motor deficits, microglia activation, synaptic dysfunction, and loss of dopaminergic neurons.”
From The Role of Microbiota-Gut-Brain Axis in Neuropsychiatric and Neurological Disorders (2021) · cites this paper as [440]
Citations
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Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases
Loh, J. S., Mak, W. Q., Tan, L. K. S., Ng, C. X., Chan, H. H., Yeow, S. H., Foo, J. B., Ong, Y. S., How, C. W., & Khaw, K. Y. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01743-1 · Cited by 1,193
The Role of Microbiota-Gut-Brain Axis in Neuropsychiatric and Neurological Disorders
Socała, K., Doboszewska, U., Szopa, A., Serefko, A., Włodarczyk, M., Zielińska, A., Poleszak, E., Fichna, J., & Wlaź, P. (2021) · Pharmacological Research · doi:10.1016/j.phrs.2021.105840 · Cited by 857
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Parkinson’s disease and gut microbiota: from clinical to mechanistic and therapeutic studies
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The Gut–Brain Axis and Its Relation to Parkinson’s Disease: A Review
Klann, E. M., Dissanayake, U., Gurrala, A., Farrer, M. J., Shukla, A. W., Ramirez‐Zamora, A., Mai, V., & Vedam‐Mai, V. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2021.782082 · Cited by 198
Metadata
- Authors
- Sun, J., Li, H., Jin, Y., Yu, J., Mao, S., Su, K.-P., Ling, Z., & Liu, J.
- Affiliations
- Wenzhou Medical University (CN)
- Taizhou Second People's Hospital (CN)
- China Medical University Hospital (TW)
- First Affiliated Hospital Zhejiang University (CN)
- Corresponding author
- Ling, Zongxin
- Liu, Jiaming
- Venue
- Brain, Behavior, and Immunity
- Publisher
- Elsevier BV
- Published
- 2021-01
- Volume
- 91
- Pages
- 703-715
- ISSN
- 0889-1591 (ISSN-L)
- OpenAlex
- W3093878129
- Cited by
- 264
- References
- 71
- Citations by year
- 2026: 43 · 2025: 60 · 2024: 56 · 2023: 47 · 2022: 42 · 2021: 16
- FWCI
- 11.36
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Brain Behavior and Immunity (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81971318)
- Topics
- Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Agricultural and Biological Sciences › Food Science › Probiotics and Fermented Foods
- Keywords
- Clostridium butyricum, Parkinson's disease, probiotics, gut microbiota, microbiota-gut-brain axis, motor impairment, MPTP-induced neurotoxicity, dopaminergic neuron loss, synaptic dysfunction, microglial activation, glucagon-like peptide-1, neuroprotection
- MeSH terms
- Gastrointestinal Microbiome, Animals, Disease Models, Animal, Male, Mice, Inbred C57BL, Parkinson Disease, RNA, Ribosomal, 16S, Neuroprotective Agents, Probiotics, Clostridium butyricum, Mice, Glucagon-Like Peptide 1, Dopaminergic Neurons
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