Gut Permeability and Microbiota in Parkinson’s Disease: Mechanistic Insights and Experimental Therapeutic Strategies

Globally, Parkinson’s disease (PD) is the neurodegenerative condition with the most rapidly increasing prevalence, and a growing body of evidence associates its pathology with impairments in the gut–brain axis. Traditionally viewed as a disease marked by the loss of dopaminergic neurons, emerging ev...

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Published in:International journal of molecular sciences Vol. 26; no. 19; p. 9593
Main Authors: Liang, Yicheng, Zhao, Yuhang, Fasano, Alessio, Su, Chien-Wen
Format: Journal Article
Language:English
Published: Switzerland MDPI AG 01.10.2025
Subjects:
alpha-Synuclein - metabolism
Animals
Blood-Brain Barrier - metabolism
Celiac disease
Cytokines
Development and progression
Fatty acids
Gastrointestinal Microbiome - physiology
Gluten
Gut microbiota
Health aspects
Homeostasis
Humans
Hypotheses
Inflammation
Kinases
Metabolites
Microbiota (Symbiotic organisms)
Neurodegeneration
Neurons
Parkinson Disease - metabolism
Parkinson Disease - microbiology
Parkinson Disease - therapy
Parkinson's disease
Pathogens
Pathology
Patients
Peptides
Permeability
Proteins
Stem cells
Toxins
Type 2 diabetes
Massachusetts
gut permeability
neuroinflammation
Parkinson’s disease (PD)
leaky gut
therapeutic approaches
gut microbiota
personalized therapy
ISSN:1422-0067, 1661-6596, 1422-0067
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Abstract Globally, Parkinson’s disease (PD) is the neurodegenerative condition with the most rapidly increasing prevalence, and a growing body of evidence associates its pathology with impairments in the gut–brain axis. Traditionally viewed as a disease marked by the loss of dopaminergic neurons, emerging evidence emphasizes that chronic neuroinflammation is a driver of neurodegeneration, with gut-originating inflammation playing a crucial role. Increased intestinal permeability, often called “leaky gut,” allows harmful substances, toxins, and misfolded α-synuclein into the systemic circulation, potentially exacerbating neuroinflammation and spreading α-synuclein pathology to the brain through the vagus nerve or compromised blood–brain barrier (BBB). This review synthesizes current insights into the relationship between gut health and PD, emphasizing the importance of gut permeability in disrupting intestinal barrier function. This paper highlights innovative therapeutic approaches, particularly personalized therapies involving gut microbiome engineering, as promising strategies for restoring gut integrity and improving neurological outcomes. Modulating specific gut bacteria to enhance the synthesis of certain metabolites, notably short-chain fatty acids (SCFAs), represents a promising strategy for reducing inflammatory responses and decelerating neurodegeneration in Parkinson’s disease.
AbstractList Globally, Parkinson's disease (PD) is the neurodegenerative condition with the most rapidly increasing prevalence, and a growing body of evidence associates its pathology with impairments in the gut-brain axis. Traditionally viewed as a disease marked by the loss of dopaminergic neurons, emerging evidence emphasizes that chronic neuroinflammation is a driver of neurodegeneration, with gut-originating inflammation playing a crucial role. Increased intestinal permeability, often called "leaky gut," allows harmful substances, toxins, and misfolded α-synuclein into the systemic circulation, potentially exacerbating neuroinflammation and spreading α-synuclein pathology to the brain through the vagus nerve or compromised blood-brain barrier (BBB). This review synthesizes current insights into the relationship between gut health and PD, emphasizing the importance of gut permeability in disrupting intestinal barrier function. This paper highlights innovative therapeutic approaches, particularly personalized therapies involving gut microbiome engineering, as promising strategies for restoring gut integrity and improving neurological outcomes. Modulating specific gut bacteria to enhance the synthesis of certain metabolites, notably short-chain fatty acids (SCFAs), represents a promising strategy for reducing inflammatory responses and decelerating neurodegeneration in Parkinson's disease.
Globally, Parkinson's disease (PD) is the neurodegenerative condition with the most rapidly increasing prevalence, and a growing body of evidence associates its pathology with impairments in the gut-brain axis. Traditionally viewed as a disease marked by the loss of dopaminergic neurons, emerging evidence emphasizes that chronic neuroinflammation is a driver of neurodegeneration, with gut-originating inflammation playing a crucial role. Increased intestinal permeability, often called "leaky gut," allows harmful substances, toxins, and misfolded α-synuclein into the systemic circulation, potentially exacerbating neuroinflammation and spreading α-synuclein pathology to the brain through the vagus nerve or compromised blood-brain barrier (BBB). This review synthesizes current insights into the relationship between gut health and PD, emphasizing the importance of gut permeability in disrupting intestinal barrier function. This paper highlights innovative therapeutic approaches, particularly personalized therapies involving gut microbiome engineering, as promising strategies for restoring gut integrity and improving neurological outcomes. Modulating specific gut bacteria to enhance the synthesis of certain metabolites, notably short-chain fatty acids (SCFAs), represents a promising strategy for reducing inflammatory responses and decelerating neurodegeneration in Parkinson's disease.Globally, Parkinson's disease (PD) is the neurodegenerative condition with the most rapidly increasing prevalence, and a growing body of evidence associates its pathology with impairments in the gut-brain axis. Traditionally viewed as a disease marked by the loss of dopaminergic neurons, emerging evidence emphasizes that chronic neuroinflammation is a driver of neurodegeneration, with gut-originating inflammation playing a crucial role. Increased intestinal permeability, often called "leaky gut," allows harmful substances, toxins, and misfolded α-synuclein into the systemic circulation, potentially exacerbating neuroinflammation and spreading α-synuclein pathology to the brain through the vagus nerve or compromised blood-brain barrier (BBB). This review synthesizes current insights into the relationship between gut health and PD, emphasizing the importance of gut permeability in disrupting intestinal barrier function. This paper highlights innovative therapeutic approaches, particularly personalized therapies involving gut microbiome engineering, as promising strategies for restoring gut integrity and improving neurological outcomes. Modulating specific gut bacteria to enhance the synthesis of certain metabolites, notably short-chain fatty acids (SCFAs), represents a promising strategy for reducing inflammatory responses and decelerating neurodegeneration in Parkinson's disease.
Audience Academic
Author Liang, Yicheng
Fasano, Alessio
Su, Chien-Wen
Zhao, Yuhang
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  givenname: Yicheng
  surname: Liang
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  givenname: Yuhang
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  givenname: Alessio
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  surname: Fasano
  fullname: Fasano, Alessio
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  givenname: Chien-Wen
  surname: Su
  fullname: Su, Chien-Wen
BackLink https://www.ncbi.nlm.nih.gov/pubmed/41096858$$D View this record in MEDLINE/PubMed
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Keywords gut permeability
neuroinflammation
Parkinson’s disease (PD)
leaky gut
therapeutic approaches
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personalized therapy
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Snippet Globally, Parkinson’s disease (PD) is the neurodegenerative condition with the most rapidly increasing prevalence, and a growing body of evidence associates...
Globally, Parkinson's disease (PD) is the neurodegenerative condition with the most rapidly increasing prevalence, and a growing body of evidence associates...
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SubjectTerms alpha-Synuclein - metabolism
Animals
Blood-Brain Barrier - metabolism
Celiac disease
Cytokines
Development and progression
Fatty acids
Gastrointestinal Microbiome - physiology
Gluten
Gut microbiota
Health aspects
Homeostasis
Humans
Hypotheses
Inflammation
Kinases
Metabolites
Microbiota (Symbiotic organisms)
Neurodegeneration
Neurons
Parkinson Disease - metabolism
Parkinson Disease - microbiology
Parkinson Disease - therapy
Parkinson's disease
Pathogens
Pathology
Patients
Peptides
Permeability
Proteins
Stem cells
Toxins
Type 2 diabetes
Title Gut Permeability and Microbiota in Parkinson’s Disease: Mechanistic Insights and Experimental Therapeutic Strategies
URI https://www.ncbi.nlm.nih.gov/pubmed/41096858
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Volume 26
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