Gut Microbiota: A Novel Therapeutic Target for Parkinson’s Disease

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: June 24, 2022

Parkinson’s disease (PD) is the second most common neurodegenerative characterized by motor dysfunction. Growing evidence has demonstrated that gut dysbiosis involved in occurrence, development and progression of PD. Numerous clinical trials have identified characteristics changed microbiota profiles, preclinical studies PD animal models indicated can influence onset via increasing intestinal permeability, aggravating neuroinflammation, aggregating abnormal levels α-synuclein fibrils, oxidative stress, decreasing neurotransmitter production. The be considered promising diagnostic therapeutic targets for PD, which regulated probiotics, psychobiotics, prebiotics, synbiotics, postbiotics, fecal transplantation, diet modifications, Chinese medicine. This review summarizes recent PD-associated profiles functions, potential roles, mechanisms microbiota-targeted interventions Deciphering underlying roles will help interpret pathogenesis from new perspectives elucidate novel strategies

Language: Английский

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Therapeutics for neurodegenerative diseases by targeting the gut microbiome: from bench to bedside

Translational Neurodegeneration, Journal Year: 2024, Volume and Issue: 13(1)

Published: Feb. 27, 2024

The aetiologies and origins of neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's (PD), amyotrophic lateral sclerosis (ALS) Huntington's (HD), are complex multifaceted. A growing body evidence suggests that the gut microbiome plays crucial roles in development progression diseases. Clinicians have come to realize therapeutics targeting potential halt This narrative review examines alterations AD, PD, ALS HD, highlighting close relationship between brain Processes mediate microbiome-brain communication including immunological, vagus nerve circulatory pathways, evaluated. Furthermore, we summarize for diseases modify its metabolites, diets, probiotics prebiotics, microbial antibacterials faecal transplantation. Finally, current challenges future directions discussed.

Language: Английский

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Gut microenvironmental changes as a potential trigger in Parkinson’s disease through the gut–brain axis

Journal of Biomedical Science, Journal Year: 2022, Volume and Issue: 29(1)

Published: July 27, 2022

Abstract Parkinson’s disease (PD) is the second most common neurodegenerative attributed to synergistic effects of genetic risk and environmental stimuli. Although PD characterized by motor dysfunction resulting from intraneuronal alpha-synuclein accumulations, termed Lewy bodies, dopaminergic neuronal degeneration in substantia nigra, multiple systems are involved process, heterogenous clinical presentation progression. Genetic predisposition regarding aberrant immune responses, abnormal protein aggregation, autophagolysosomal impairment, mitochondrial leads vulnerable neurons that sensitive triggers and, together, result degeneration. Neuropathology studies have shown that, at least some patients, bodies start enteric nervous system then spread central through gut–brain axis, suggesting contribution an altered gut microenvironment pathogenesis PD. A plethora evidence has revealed different microbiomes metabolites patients with compared unaffected controls. Chronic inflammation impaired intestinal barrier integrity been observed human mouse models These observations led hypothesis a potential trigger process genetically susceptible host. In this review, we will discuss complex interplay between factors microenvironmental changes contributing pathogenesis.

Language: Английский

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The Interplay between Gut Microbiota and Parkinson’s Disease: Implications on Diagnosis and Treatment

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(20), P. 12289 - 12289

Published: Oct. 14, 2022

The bidirectional interaction between the gut microbiota (GM) and Central Nervous System, so-called brain axis (GMBA), deeply affects function has an important impact on development of neurodegenerative diseases. In Parkinson’s disease (PD), gastrointestinal symptoms often precede onset motor non-motor manifestations, alterations in GM composition accompany pathogenesis. Several studies have been conducted to unravel role dysbiosis intestinal permeability PD progression, but therapeutic diagnostic applications modifying approaches remain be fully elucidated. After a brief introduction involvement GMBA disease, we present evidence for leaky patients. According these data, then review potential GM-based signatures serve as biomarkers highlight emerging probiotics, prebiotics, antibiotics, dietary interventions, fecal transplantation supportive PD. Finally, analyze mutual influence commonly prescribed medications gut-microbiota, offer insights also nasal oral pathology, thus providing comprehensive up-to-date overview microbial features diagnosis treatment.

Language: Английский

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Health and Disease: Akkermansia muciniphila , the Shining Star of the Gut Flora

Research, Journal Year: 2023, Volume and Issue: 6

Published: Jan. 1, 2023

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Mechanistic Insights Into Gut Microbiome Dysbiosis-Mediated Neuroimmune Dysregulation and Protein Misfolding and Clearance in the Pathogenesis of Chronic Neurodegenerative Disorders

Frontiers in Neuroscience, Journal Year: 2022, Volume and Issue: 16

Published: Feb. 25, 2022

The human gut microbiota is a complex, dynamic, and highly diverse community of microorganisms. Beginning as early in utero fetal development continuing through birth to late-stage adulthood, the crosstalk between microbiome brain essential for modulating various metabolic, neurodevelopmental, immune-related pathways. Conversely, microbial dysbiosis – defined alterations richness relative abundances implicated pathogenesis several chronic neurological neurodegenerative disorders. Evidence from large-population cohort studies suggests that individuals with conditions have an altered composition well serum metabolomic profiles distinct those healthy population. Dysbiosis also linked psychiatric gastrointestinal complications comorbidities often associated prodromal phase Parkinson’s disease (PD) Alzheimer’s (AD). Studies identified potential mediators link Recent findings elucidated mechanisms pathology enteric nervous system prior onset neurodegeneration. This review highlights functional pathways mechanisms, particularly microbe-induced inflammation, protein misfolding, propagation disease-specific pathology, defective clearance, autoimmune dysregulation, linking In addition, we discuss how pathogenic transformation leads increased endotoxin production fewer beneficial metabolites, both which could trigger immune cell activation neuronal dysfunction. These can further disrupt intestinal barrier permeability, aggravate systemic pro-inflammatory state, impair blood–brain permeability recruit leading neuroinflammation Continued biomedical advances understanding microbiota-gut-brain axis will extend frontier disorders enable utilization novel diagnostic therapeutic strategies mitigate pathological burden these diseases.

Language: Английский

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Gut mucosal cells transfer α-synuclein to the vagus nerve

JCI Insight, Journal Year: 2023, Volume and Issue: 8(23)

Published: Dec. 7, 2023

Clinical and experimental data indicate that the gut may play a role in PD susceptibility.Not only do gastrointestinal symptoms such as constipation often precede motor of (22)(23)(24), experimentally, it has been suggested rodent models exogenous α-synuclein fibrils introduced into can spread to brain (25-27).Abnormal aggregates have histopathologically identified enteric nervous system prior development (22).Evidence supporting for involvement pathology includes observation immunoreactive inclusions localize neurons submucosal plexus, whose axons project mucosa (28-30) myenteric parallel input vagus nerve (31).Mice harboring A53T transgene exhibited dysfunction including increased colonic transit times reduced fecal output consistent with (32, 33).In animals, vagal route transport also documented following exposure environmental toxicant rotenone cause misfolding (34), well direct injections adeno-associated viral vectors overexpressing human (35).More recently, was demonstrated vagotomy prevented formation when were injected susceptible mice, indicating pathogenic from terminals (25, 36).However, physiologically relevant origins misfolded protein might use conduit (or out of) unclear.One clue be some epidemiological observations suggest complete truncal patients is associated decreased risk PD, suggesting at least cases aggregation critical later on (37-39).Recently, discovered enteroendocrine cells (EECs) connect culture intact mice (40).Using modified rabies tracing vivo, synaptic connection verified between peptide YY-expressing EECs colon (40).In coculture experiments dishes, cholecystokinin-containing (CCK-containing) sensory form spontaneous connections (40, 41).Thus, there appears an inherent affinity (42).EECs are exposed lumen respond numerous chemical physical stimuli diet, microbiome, environment (40,(43)(44)(45).Long thought produce exclusively hormones, now known possess neuron-like properties, part phenotype include endogenous expression (42,46).EECs express neurotransmitters other canonical presynaptic proteins axon-like processes sometimes called neuropods through which they nearby nerves 41).To explore potential cellular source pathological contribute seeding activity brain, here we organoids transgenic whether mucosal nerve.

Language: Английский

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Potential Effects of Akkermansia Muciniphila in Aging and Aging-Related Diseases: Current Evidence and Perspectives

Aging and Disease, Journal Year: 2023, Volume and Issue: 14(6), P. 2015 - 2015

Published: Jan. 1, 2023

Akkermansia muciniphila (A. muciniphila) is an anaerobic bacterium that widely colonizes the mucus layer of human and animal gut. The role this symbiotic in host metabolism, inflammation, cancer immunotherapy has been extensively investigated over past 20 years. Recently, a growing number studies have revealed link between A. muciniphila, aging aging-related diseases (ARDs). Research area gradually shifting from correlation analysis to exploration causal relationships. Here, we systematically reviewed association with ARDs (including vascular degeneration, neurodegenerative diseases, osteoporosis, chronic kidney disease, type 2 diabetes). Furthermore, summarize potential mechanisms action offer perspectives for future studies.

Language: Английский

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Endoplasmic reticulum stress: A possible connection between intestinal inflammation and neurodegenerative disorders

Neurogastroenterology & Motility, Journal Year: 2024, Volume and Issue: 36(5)

Published: March 10, 2024

Abstract Background Different studies have shown the key role of endoplasmic reticulum (ER) stress in autoimmune and chronic inflammatory disorders, as well neurodegenerative diseases. ER leads to formation misfolded proteins which affect secretion different cell types that are crucial for intestinal homeostasis. Purpose In this review, we discuss its involvement development bowel diseases, conditions can cause severe damage gastrointestinal tract, focusing on alteration Paneth cells goblet (the principal secretory phenotypes epithelial cells). is also discussed context protein misfolding represents signature mechanism. consequent accumulation might represent a bridge between inflammation neurodegeneration along gut‐to‐brain axis, affecting homeostasis equilibrium commensal microbiota. Targeting could foster future designing new biomarkers therapeutic approaches disorders.

Language: Английский

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Discovery of a Gut Bacterial Metabolic Pathway that Drives α-Synuclein Aggregation

ACS Chemical Biology, Journal Year: 2024, Volume and Issue: 19(4), P. 1011 - 1021

Published: March 22, 2024

Parkinson's disease (PD) etiology is associated with aggregation and accumulation of α-synuclein (α-syn) proteins in midbrain dopaminergic neurons. Emerging evidence suggests that certain subtypes PD, α-syn aggregates originate the gut subsequently spread to brain. However, mechanisms instigate have remained elusive. In brain, induced by oxidized dopamine. Such a mechanism has not been explored context gastrointestinal tract, niche harboring 46% body's dopamine reservoirs. Here, we report

Language: Английский

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