Abstract
Background: Increased gut permeability (leaky gut) and alterations in gut microbiota are now widely accepted as relevant to the etiology, course and treatment of many neuropsychiatric disorders, including Parkinson disease (PD). Although a wide array of data on the biological underpinnings of PD has not yet been linked to such gut-associated changes, increased gut permeability and dysregulated microbiota alter many pathways germane to PD.
Methods: In this article we review and integrate these wider biological changes in PD, including increased oxidative and nitrosative stress, immune-inflammatory processes, tryptophan catabolites and alterations in serotoninergic and melatoninergic pathways.
Results: These wider biological changes in PD are compatible with alterations in gut permeability and changes in gut microbiota. By driving tryptophan down the kynurenine pathway, pro-inflammatory cytokines and chronic stress-driven activation of the hypothalamic-pituitary-adrenal axis decrease the availability of serotonin as a precursor for activation of the melatonergic pathways.
Conclusion: Decreased local melatonin synthesis in glia, gut, neuronal and immune cells is likely to be important to the etiology, course and management of PD.
Keywords: Parkinson disease, gut microbiota, gut permeability, leaky gut, melatonin, alpha 7 nicotinic, tryptophan catabolites.
Current Pharmaceutical Design
Title:Gut Permeability and Microbiota in Parkinson’s Disease: Role of Depression, Tryptophan Catabolites, Oxidative and Nitrosative Stress and Melatonergic Pathways
Volume: 22 Issue: 40
Author(s): George Anderson, Moonsang Seo, Michael Berk, Andre F. Carvalho and Michael Maes
Affiliation:
Keywords: Parkinson disease, gut microbiota, gut permeability, leaky gut, melatonin, alpha 7 nicotinic, tryptophan catabolites.
Abstract: Background: Increased gut permeability (leaky gut) and alterations in gut microbiota are now widely accepted as relevant to the etiology, course and treatment of many neuropsychiatric disorders, including Parkinson disease (PD). Although a wide array of data on the biological underpinnings of PD has not yet been linked to such gut-associated changes, increased gut permeability and dysregulated microbiota alter many pathways germane to PD.
Methods: In this article we review and integrate these wider biological changes in PD, including increased oxidative and nitrosative stress, immune-inflammatory processes, tryptophan catabolites and alterations in serotoninergic and melatoninergic pathways.
Results: These wider biological changes in PD are compatible with alterations in gut permeability and changes in gut microbiota. By driving tryptophan down the kynurenine pathway, pro-inflammatory cytokines and chronic stress-driven activation of the hypothalamic-pituitary-adrenal axis decrease the availability of serotonin as a precursor for activation of the melatonergic pathways.
Conclusion: Decreased local melatonin synthesis in glia, gut, neuronal and immune cells is likely to be important to the etiology, course and management of PD.
Export Options
About this article
Cite this article as:
Anderson George, Seo Moonsang, Berk Michael, Carvalho F. Andre and Maes Michael, Gut Permeability and Microbiota in Parkinson’s Disease: Role of Depression, Tryptophan Catabolites, Oxidative and Nitrosative Stress and Melatonergic Pathways, Current Pharmaceutical Design 2016; 22 (40) . https://dx.doi.org/10.2174/1381612822666160906161513
DOI https://dx.doi.org/10.2174/1381612822666160906161513 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
Blood-based biomarkers in large-scale screening for neurodegenerative diseases
Disease biomarkers are necessary tools that can be employ in several clinical context of use (COU), ranging from the (early) diagnosis, prognosis, prediction, to monitor of disease state and/or drug efficacy. Regarding neurodegenerative diseases, in particular Alzheimer’s disease (AD), a battery of well-validated biomarkers are available, such as cerebrospinal fluid ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Diabetes mellitus: advances in diagnosis and treatment driving by precision medicine
Diabetes mellitus (DM) is a chronic degenerative metabolic disease with ever increasing prevalence worldwide which is now an epidemic disease affecting 500 million people worldwide. Insufficient insulin secretion from pancreatic β cells unable to maintain blood glucose homeostasis is the main feature of this disease. Multifactorial and complex nature of ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Social Markers of Mild Cognitive Impairment: Proportion of Word Counts in Free Conversational Speech
Current Alzheimer Research Tuberculostatic Drugs Targeting Infections of the Central Nervous System
Anti-Infective Agents Patent Selections
Recent Patents on Materials Science Withdrawal Notice: Evaluation of Clinical Profile, Diagnostic Tests, And Prognosis of Crypto-coccal Meningitis in HIV Infected Patients in Western India
Infectious Disorders - Drug Targets Structural Chromosome Abnormalities Associated with Obesity: Report of Four New Subjects and Review of Literature
Current Genomics The Insulin-like Growth Factor-1 Axis and its Potential as a Therapeutic Target in Central Nervous System (CNS) Disorders
Central Nervous System Agents in Medicinal Chemistry Microbial Immune Evasion Employing Suppressor of Cytokine Signaling (SOCS) Proteins
Inflammation & Allergy - Drug Targets (Discontinued) Magnetic Resonance Imaging Findings of Foetal Congenital Toxoplasma Encephalitis: A Case Report
Current Medical Imaging Onset Age and Clinical Heterogeneity of Dementias: A Diagnostic and Therapeutic Approach
Current Psychopharmacology Stem Cell Genetic Therapy for Fanconi Anemia – A New Hope
Current Gene Therapy Role of Nanotechnology for Enzyme Replacement Therapy in Lysosomal Diseases. A Focus on Gaucher’s Disease
Current Medicinal Chemistry DLPF Targeted Repetitive Transcranial Magnetic Stimulation Improves Brain Glucose Metabolism Along with the Clinical and Electrophysiological Parameters in CBD Patients
Endocrine, Metabolic & Immune Disorders - Drug Targets Imaging Malignant Gliomas with 99mTc-MIBI Brain Single-Photon Emission Computed Tomography
Current Medical Imaging Serum S-100B Protein as A Biochemical Marker of Brain Injury: A Review of Current Concepts
Current Medicinal Chemistry The Prevalence of Early Toxoplasmosis after Bone Marrow Transplantation Using PCR: A Study in Iranian Patients
Infectious Disorders - Drug Targets Development of a Registry for Down Syndrome in the Gulf Area of the Middle East
Applied Clinical Research, Clinical Trials and Regulatory Affairs Novel Agents in CNS Myeloma Treatment
Central Nervous System Agents in Medicinal Chemistry Tissue-Specific Methylation of Long Interspersed Nucleotide Element-1 of Homo Sapiens (L1Hs) During Human Embryogenesis and Roles in Neural Tube Defects
Current Molecular Medicine Alzheimers Disease (AD) and Mild Cognitive Impairment (MCI) Patients are Characterized by Increased BDNF Serum Levels
Current Alzheimer Research Recent Advances in Nanotechnology-Based Drug Delivery Approaches for Alzheimer disease
Current Drug Targets