ArticleMolecular neurodegeneration2024
Gut-first Parkinson's disease is encoded by gut dysbiome.
Article in Molecular neurodegeneration, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 1 of them a synthesis that pooled it.
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Who cites it
43 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Gut-brain axis dysfunction in Parkinson's disease: a meta-analysis of microbiome dysbiosis and intestinal barrier markers.Frontiers in medicine · 2026Pooled it
- Review
- Review
- Article
- Astrocytic HSP90AA1 Upregulation and Altered Synaptic Signaling in Parkinson's Disease: Transcriptomic Screening and In Vivo Validation.International journal of molecular sciences · 2026Article
- Review
- Gut microbiota in health and disease.Molecular biomedicine · 2026Review
- 6-Shogaol Complements Levodopa Therapy by Modulating Brain-Gut Metabolomes in a Parkinson's Disease Model.Biomolecules & therapeutics · 2026Article
- Gut Microbiome Dysbiosis in Metabolic Syndrome: Current Evidence and Emerging Perspectives.Nutrients · 2026Review
- Association Between Blood-Brain Barrier Disruption and Gut Microbiota Dysbiosis in Parkinson's Disease.Cellular and molecular neurobiology · 2026Review
- Review
- Isotopically enrichedScientific reports · 2026Article
- Hair metal dysregulation in Parkinson's disease: Implications for diagnosis and gut-brain axis involvement.iScience · 2026Article
- Evodiamine alleviates MPTP-induced Parkinson's disease in mice by regulating gut microbiota and suppressing TLR4/MyD88/NF-kB pathway.Scientific reports · 2026Article
- The lung-brain axis: elucidating the mechanisms of pulmonary-driven neurological disorders.Journal of neuroinflammation · 2026Review
- Bacteroides coprocola protects dopaminergic neurons in rotenone-induced Parkinson's disease mouse model by modulating gut microbiota dysbiosis and inhibiting the NLRP3 signaling pathway.Translational neurodegeneration · 2026Article
- Gut microbiota and Parkinson's disease: exploring pathogenesis and potential therapeutic strategies from a gut-brain axis perspective.iScience · 2026Review
- enGLOW 3D microscopy of the enteric nervous system in cleared human and mouse gut.Communications biology · 2026Article
- Beyond the Brain: Exploring the multi-organ axes in Parkinson's disease pathogenesis.Journal of advanced research · 2026Review
- Lifestyle medicine in Parkinson's disease.Journal of neural transmission (Vienna, Austria : 1996) · 2026Review
Corrections and comments
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Authors and funding
19 authors.
Funding
Abstract
backgroundIn Parkinson's patients, intestinal dysbiosis can occur years before clinical diagnosis, implicating the gut and its microbiota in the disease. Recent evidence suggests the gut microbiota may trigger body-first Parkinson Disease (PD), yet the underlying mechanisms remain unclear. This study aims to elucidate how a dysbiotic microbiome through intestinal immune alterations triggers PD-related neurodegeneration.
methodsTo determine the impact of gut dysbiosis on the development and progression of PD pathology, wild-type male C57BL/6 mice were transplanted with fecal material from PD patients and age-matched healthy donors to challenge the gut-immune-brain axis.
resultsThis study demonstrates that patient-derived intestinal microbiota caused midbrain tyrosine hydroxylase positive (TH +) cell loss and motor dysfunction. Ileum-associated microbiota remodeling correlates with a decrease in Th17 homeostatic cells. This event led to an increase in gut inflammation and intestinal barrier disruption. In this regard, we found a decrease in CD4 + cells and an increase in pro-inflammatory cytokines in the blood of PD transplanted mice that could contribute to an increase in the permeabilization of the blood-brain-barrier, observed by an increase in mesencephalic Ig-G-positive microvascular leaks and by an increase of mesencephalic IL-17 levels, compatible with systemic inflammation. Furthermore, alpha-synuclein aggregates can spread caudo-rostrally, causing fragmentation of neuronal mitochondria. This mitochondrial damage subsequently activates innate immune responses in neurons and triggers microglial activation.
conclusionsWe propose that the dysbiotic gut microbiome (dysbiome) in PD can disrupt a healthy microbiome and Th17 homeostatic immunity in the ileum mucosa, leading to a cascade effect that propagates to the brain, ultimately contributing to PD pathophysiology. Our landmark study has successfully identified new peripheral biomarkers that could be used to develop highly effective strategies to prevent the progression of PD into the brain.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.