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Gut Microbiota-Based Interventions for Parkinson's Disease: Neuroprotective Mechanisms and Current Perspective.

作者信息

Kumar Deepak, Bishnoi Mahendra, Kondepudi Kanthi Kiran, Sharma Shyam Sunder

机构信息

Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, S.A.S. Nagar, Mohali, Punjab, 160062, India.

Centre for Excellence in Functional Foods, Division of Food and Nutritional Biotechnology, National Agri-Food Biomanufacturing Institute (NABI), Knowledge City-Sector 81, S.A.S. Nagar, Punjab, 140306, India.

出版信息

Probiotics Antimicrob Proteins. 2025 Jan 15. doi: 10.1007/s12602-024-10433-x.


DOI:10.1007/s12602-024-10433-x
PMID:39809955
Abstract

Recent evidence links gut microbiota alterations to neurodegenerative disorders, including Parkinson's disease (PD). Replenishing the abnormal composition of gut microbiota through gut microbiota-based interventions "prebiotics, probiotics, synbiotics, postbiotics, and fecal microbiota transplantation (FMT)" has shown beneficial effects in PD. These interventions increase gut metabolites like short-chain fatty acids (SCFAs) and glucagon-like peptide-1 (GLP-1), which may protect dopaminergic neurons via the gut-brain axis. Neuroprotective effects of these interventions are mediated by several mechanisms, including the enhancement of neurotrophin and activation of the PI3K/AKT/mTOR signaling pathway, GLP-1-mediated gut-brain axis signaling, Nrf2/ARE pathway, and autophagy. Other pathways, such as free fatty acid receptor activation, synaptic plasticity improvement, and blood-brain and gut barrier integrity maintenance, also contribute to neuroprotection. Furthermore, the inhibition of the TLR4/NF-кB pathway, MAPK pathway, GSK-3β signaling pathway, miR-155-5p-mediated neuroinflammation, and ferroptosis could account for their protective effects. Clinical studies involving gut microbiota-based interventions have shown therapeutic benefits in PD patients, particularly in improving gastrointestinal dysfunction and some neurological symptoms. However, the effectiveness in alleviating motor symptoms remains mild. Large-scale clinical trials are still needed to confirm these findings. This review emphasizes the neuroprotective mechanisms of gut microbiota-based interventions in PD as supported by both preclinical and clinical studies.

摘要

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引用本文的文献

[1]
The microbiota-gut-brain axis and central nervous system diseases: from mechanisms of pathogenesis to therapeutic strategies.

Front Microbiol. 2025-6-13

[2]
Dietary live microbe intake and its association with Parkinson's disease in American adults: an NHANES analysis (1999-2018).

Front Nutr. 2025-5-29

[3]
A Review of the Influence of Prebiotics, Probiotics, Synbiotics, and Postbiotics on the Human Gut Microbiome and Intestinal Integrity.

J Clin Med. 2025-5-23

[4]
Peroxisome Proliferator-Activated Receptors (PPARs) May Mediate the Neuroactive Effects of Probiotic Metabolites: An In Silico Approach.

Int J Mol Sci. 2025-5-9

[5]
Impact of fecal microbiota transplantation on lung function and gut microbiome in an ARDS rat model: A multi-omics analysis including 16S rRNA sequencing, metabolomics, and transcriptomics.

Int J Immunopathol Pharmacol. 2025

[6]
Rotenone Induces Parkinsonism with Constipation Symptoms in Mice by Disrupting the Gut Microecosystem, Inhibiting the PI3K-AKT Signaling Pathway and Gastrointestinal Motility.

Int J Mol Sci. 2025-2-27

本文引用的文献

[1]
Relationship among Parkinson's disease, constipation, microbes, and microbiological therapy.

World J Gastroenterol. 2024-1-21

[2]
Supplementation of probiotic Bifidobacterium breve Bif11 reverses neurobehavioural deficits, inflammatory changes and oxidative stress in Parkinson's disease model.

Neurochem Int. 2024-3

[3]
The intestinal microbiota exerts a sex-specific influence on neuroinflammation in a Parkinson's disease mouse model.

Neurochem Int. 2024-2

[4]
Gut dysbiosis: Ecological causes and causative effects on human disease.

Proc Natl Acad Sci U S A. 2023-12-12

[5]
Autophagy in Parkinson's Disease.

Biomolecules. 2023-9-22

[6]
Neuroprotective effects of an engineered Nissle 1917 on Parkinson's disease in mice by delivering GLP-1 and modulating gut microbiota.

Bioeng Transl Med. 2022-6-18

[7]
Fecal Microbiota Transplantation from Aged Mice Render Recipient Mice Resistant to MPTP-Induced Nigrostriatal Degeneration Via a Neurogenesis-Dependent but Inflammation-Independent Manner.

Neurotherapeutics. 2023-9

[8]
Effect of strain Shirota supplementation on clinical responses and gut microbiome in Parkinson's disease.

Food Funct. 2023-7-31

[9]
The Microbiota-Gut-Brain Axis in Behaviour and Brain Disorders.

Int J Mol Sci. 2023-5-9

[10]
Neuroprotective effect of engineered butyricum-pMTL007-GLP-1 on Parkinson's disease mice models via promoting mitophagy.

Bioeng Transl Med. 2023-3-17

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