Published: Jan. 1, 2024
Language: Английский
Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)
Published: Feb. 16, 2024
Abstract The human gastrointestinal tract is populated with a diverse microbial community. vast genetic and metabolic potential of the gut microbiome underpins its ubiquity in nearly every aspect biology, including health maintenance, development, aging, disease. advent new sequencing technologies culture-independent methods has allowed researchers to move beyond correlative studies toward mechanistic explorations shed light on microbiome–host interactions. Evidence unveiled bidirectional communication between central nervous system, referred as “microbiota–gut–brain axis”. microbiota–gut–brain axis represents an important regulator glial functions, making it actionable target ameliorate development progression neurodegenerative diseases. In this review, we discuss mechanisms As provides essential cues microglia, astrocytes, oligodendrocytes, examine communications microbiota these cells during healthy states Subsequently, diseases using metabolite-centric approach, while also examining role microbiota-related neurotransmitters hormones. Next, targeting intestinal barrier, blood–brain meninges, peripheral immune system counteract dysfunction neurodegeneration. Finally, conclude by assessing pre-clinical clinical evidence probiotics, prebiotics, fecal transplantation A thorough comprehension will foster effective therapeutic interventions for management
Language: Английский
Citations
231
Current Neurology and Neuroscience Reports, Journal Year: 2024, Volume and Issue: 24(6), P. 163 - 179
Published: April 20, 2024
Language: Английский
Citations
16
npj Parkinson s Disease, Journal Year: 2024, Volume and Issue: 10(1)
Published: May 21, 2024
Abstract We aimed to identify gut microbial features in Parkinson’s disease (PD) across countries by meta-analyzing our fecal shotgun sequencing dataset of 94 PD patients and 73 controls Japan with five previously reported datasets from USA, Germany, China1, China2, Taiwan. GC-MS LC-MS/MS assays were established quantify short-chain fatty acids (SCFAs) polyamines, respectively. α-Diversity was increased six datasets. Taxonomic analysis showed that species Akkermansia muciniphila PD, while Roseburia intestinalis Faecalibacterium prausnitzii decreased PD. Pathway genes the biosyntheses riboflavin biotin markedly after adjusting for confounding factors. Five out categories carbohydrate-active enzymes (CAZymes) Metabolomic samples revealed SCFAs polyamines significantly Genes positively correlated concentrations polyamines. Bacteria accounted biosynthesis Japan, Germany different those Similarly, bacteria two country groups. postulate reduce intestinal mucus layer, which subsequently facilitates formation abnormal α-synuclein fibrils neural plexus also cause neuroinflammation
Language: Английский
Citations
11
Molecular Neurodegeneration, Journal Year: 2025, Volume and Issue: 20(1)
Published: Jan. 30, 2025
Abstract Gastrointestinal (GI) involvement in Lewy body diseases (LBDs) has been observed since the initial descriptions of patients by James Parkinson. Recent experimental and human observational studies raise possibility that pathogenic alpha-synuclein (⍺-syn) might develop GI tract subsequently spread to susceptible brain regions. The cellular mechanistic origins ⍺-syn propagation disease are under intense investigation. Experimental LBD models have implicated important contributions from intrinsic gut microbiome, intestinal immune system, environmental toxicants, acting as triggers modifiers pathologies. Here, we review primary clinical observations link dysfunctions LBDs. We first provide an overview anatomy repertoire relevant for disease, with a focus on luminal-sensing cells epithelium including enteroendocrine express make direct contact nerves. describe interactions within resident microbes exogenous how these may directly contribute pathology along related metabolic immunological responses. Finally, critical knowledge gaps field highlighted, focusing pivotal questions remain some 200 years after dysfunction predict better understanding pathophysiologies influence risk progression will accelerate discoveries lead deeper overall potential therapeutic strategies targeting gut-brain axis delay, arrest, or prevent progression.
Language: Английский
Citations
1
CNS Drugs, Journal Year: 2024, Volume and Issue: 38(5), P. 315 - 331
Published: April 3, 2024
The concept of a 'microbiota-gut-brain axis' has recently emerged as an important player in the pathophysiology Parkinson disease (PD), not least because reciprocal interaction between gut bacteria and medications. microbiota can influence levodopa kinetics, conversely, drugs administered for PD composition. Through two-step enzymatic pathway, microbes decarboxylate to dopamine small intestine then dehydroxylate it m-tyramine, thus reducing availability. Inhibition bacterial decarboxylation pathways could therefore represent strategy increase absorption. Other perturbations common PD, such intestinal overgrowth Helicobacter pylori infection, also modulate metabolism, eradication therapies may improve Interventions targeting offer novel opportunity manage disabling motor complications dopa-unresponsive symptoms. Mediterranean diet-induced changes composition might range non-motor Prebiotics levels short-chain fatty acid-producing decrease pro-inflammatory species, with positive effects on clinical symptoms kinetics. Different formulations probiotics showed beneficial outcomes constipation, some them improving levels; however, most effective dosage duration long-term these treatments remain unknown. Data from faecal transplantation studies are preliminary, but show encouraging trends towards improvement both outcomes.This article summarises up-to-date knowledge pharmacomicrobiomics discusses how manipulation represents potential new therapeutic avenue PD.
Language: Английский
Citations
7
Published: March 5, 2024
Neurological disorders are the leading cause of cognitive and physical disability worldwide, affecting 15% global population. Due to demographics aging, prevalence neurological disorders, including neurodegenerative diseases, will double over next two decades. Unfortunately, while available therapies provide symptomatic relief for motor impairment, there is an urgent unmet need develop disease-modifying that slow rate pathological progression. In context, biomarkers could identify at-risk prodromal patients, monitor disease progression, track response therapy, parse causality molecular events novel targets further clinical investigation. Thus, identifying discriminate between diseases reflect specific stages pathology would catalyze discovery development therapeutic targets. This review describe prevalence, known mechanisms, ongoing or recently concluded trials, three most prevalent Alzheimer’s (AD), amyotrophic lateral sclerosis (ALS), Parkinson’s (PD).
Language: Английский
Citations
6
Biomolecules, Journal Year: 2024, Volume and Issue: 14(4), P. 398 - 398
Published: March 26, 2024
Neurological disorders are the leading cause of cognitive and physical disability worldwide, affecting 15% global population. Due to demographics aging, prevalence neurological disorders, including neurodegenerative diseases, will double over next two decades. Unfortunately, while available therapies provide symptomatic relief for motor impairment, there is an urgent unmet need develop disease-modifying that slow rate pathological progression. In context, biomarkers could identify at-risk prodromal patients, monitor disease progression, track responses therapy, parse causality molecular events novel targets further clinical investigation. Thus, identifying discriminate between diseases reflect specific stages pathology would catalyze discovery development therapeutic targets. This review describe prevalence, known mechanisms, ongoing or recently concluded trials, three most prevalent Alzheimer’s (AD), amyotrophic lateral sclerosis (ALS), Parkinson’s (PD).
Language: Английский
Citations
5
Life Sciences, Journal Year: 2024, Volume and Issue: 357, P. 123088 - 123088
Published: Sept. 30, 2024
Language: Английский
Citations
4
Neurologic Clinics, Journal Year: 2025, Volume and Issue: 43(2), P. 209 - 228
Published: Jan. 22, 2025
Language: Английский
Citations
0
Movement Disorders Clinical Practice, Journal Year: 2025, Volume and Issue: unknown
Published: March 13, 2025
Abstract Background The gut‐brain axis, i.e. the bidirectional communication system between gut and brain, has become of central importance in Parkinson disease (PD) research over past 20 years. Aims We aimed to describe milestones axis PD development theories proposing involvement gastrointestinal tract pathogenesis. Methods searched PubMed using terms ‘gut‐brain axis’ AND ‘Parkinson disease’, selected relevant articles provide foundation for reconstructing an historical overview PD. Results Mounting evidence from preclinical, clinical post‐mortem studies suggests that a subgroup patients present with range prodromal symptoms (e.g., autonomic dysfunction, rapid eye movement sleep behaviour disorder) which reflect initial accumulation later spread pathological α‐synuclein rostrally (“body‐first” PD). Through neural connections along may producing clinically manifest disease. Recently, two mechanisms involving have attracted increasing attention their role pathogenesis progression, namely perturbation composition microorganisms living (the microbiome), dysfunction enteroendocrine cells. Conclusion Treatments targeting especially microbiome cells pathway, could potentially slow progression or even prevent onset. Among these, pre/probiotics, faecal microbiota transplantation, glucagon‐like peptide‐1 receptor agonists, entered advanced stages trials humans shown potential symptomatic disease‐modifying effects.
Language: Английский
Citations
0