Gut-first Parkinson’s disease is encoded by gut dysbiome

Molecular Neurodegeneration, Journal Year: 2024, Volume and Issue: 19(1)

Published: Oct. 24, 2024

Abstract Background In Parkinson's patients, intestinal dysbiosis can occur years before clinical diagnosis, implicating the gut and its microbiota in disease. Recent evidence suggests may trigger body - first Parkinson Disease (PD), yet underlying mechanisms remain unclear. This study aims to elucidate how a dysbiotic microbiome through immune alterations triggers PD related neurodegeneration. Methods To determine impact of on development progression pathology, wild-type male C57BL/6 mice were transplanted with fecal material from patients age matched healthy donors challenge gut-immune-brain axis. Results demonstrates that patient-derived caused midbrain tyrosine hydroxylase positive (TH +) cell loss motor dysfunction. Ileum-associated remodeling correlates decrease Th17 homeostatic cells. event led an increase inflammation barrier disruption. this regard, we found CD4 + cells pro-inflammatory cytokines blood could contribute permeabilization blood–brain-barrier, observed by mesencephalic Ig G microvascular leaks IL 17 levels, compatible systemic inflammation. Furthermore, alpha-synuclein aggregates spread caudo-rostrally, causing fragmentation neuronal mitochondria. mitochondrial damage subsequently activates innate responses neurons microglial activation. Conclusions We propose (dysbiome) disrupt immunity ileum mucosa, leading cascade effect propagates brain, ultimately contributing pathophysiology. Our landmark has successfully identified new peripheral biomarkers be used develop highly effective strategies prevent into brain. Graphical

Language: Английский

---

A Low-Protein, High-Carbohydrate Diet Exerts a Neuroprotective Effect on Mice with 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine-Induced Parkinson’s Disease by Regulating the Microbiota-Metabolite–Brain Axis and Fibroblast Growth Factor 21

Journal of Agricultural and Food Chemistry, Journal Year: 2023, Volume and Issue: 71(23), P. 8877 - 8893

Published: June 2, 2023

Parkinson's disease (PD) is closely linked to lifestyle factors, particularly dietary patterns, which have attracted interest as potential disease-modifying factors. Eating a low-protein, high-carbohydrate (LPHC) diet promising intervention against brain aging; however, its protective effect on PD remains elusive. Here, we found that an LPHC ameliorated 1-methyl-4-phenyl-1,2,3,6-tetrathydropyridine (MPTP)-induced motor deficits, decreased dopaminergic neuronal death, and increased the levels of striatal dopamine, serotonin, their metabolites in mice. Levels fibroblast growth factor 21 (FGF-21), member family, were elevated mice following treatment. Furthermore, administration FGF-21 exerted MPTP-induced PC12 cells, similar Sequencing 16S rDNA from fecal microbiota revealed normalized gut bacterial composition imbalance mice, evidenced by abundance genera Bifidobacterium, Ileibacterium, Turicibacter, Blautia Bilophila, Alistipes, Bacteroides. PICRUSt-predicted microbiome function suppressed lipopolysaccharide biosynthesis citrate cycle (TCA cycle), ubiquinone other terpenoid-quinones, oxidative phosphorylation pathways caused MPTP, enhanced amino acids, carbohydrate metabolism, secondary metabolites. A nonmetabolomic analysis serum feces showed significantly aromatic acids (AAAs), including tryptophan, tyrosine, phenylalanine. In addition, concentrations bile (BAs), tauroursodeoxycholic acid (TUDCA) taurine. Collectively, our current findings point mechanism administering attenuating movement impairments with AAAs, microbial (TUDCA taurine), key mediators along gut-microbiota-brain axis.

Language: Английский

---

Unravelling the mechanisms of underweight in Parkinson’s disease by investigating into the role of gut microbiome

npj Parkinson s Disease, Journal Year: 2024, Volume and Issue: 10(1)

Published: Jan. 24, 2024

Abstract Approximately half of patients with Parkinson’s disease (PD) suffer from unintentional weight loss and are underweight, complicating the clinical course PD patients. Gut microbiota alteration has been proven to be associated PD, recent studies have shown that gut could lead muscle wasting, implying a possible role in underweight PD. In this study, we aimed (1) investigate mechanism underlying respect (2) estimate extent which may mediate PD-related through mediation analysis. The data were adapted Hill‐Burns et al., 330 participants (199 131 controls) enrolled study. Fecal samples collected for microbiome 16S rRNA gene sequence processed using DADA2. Mediation analysis was performed quantify effect intestinal microbial on causal identify key bacteria significantly mediated underweight. results showed group had more (body mass index (BMI) < 18.5) after controlling age sex. Ten genera four species different relative abundance between non-underweight individuals group. 42.29% 37.91% alterations at genus levels, respectively. Five (Agathobacter, Eisenbergiella, Fusicatenibacter, Roseburia, Ruminococcaceae_UCG_013) significant effects. conclusion, found up cases by microbiota, increased pro-inflammatory decreased SCFA-producing bacteria, indicates state, disturbance metabolism, interference appetite regulation involved

Language: Английский

---

Microbiota Dysbiosis in Parkinson Disease—In Search of a Biomarker

Biomedicines, Journal Year: 2022, Volume and Issue: 10(9), P. 2057 - 2057

Published: Aug. 23, 2022

Numerous studies have highlighted the role of gastrointestinal system in Parkinson disease pathogenesis. It is likely triggered by proinflammatory markers produced specific gut bacteria. This review's aim to identify bacterial biomarkers disease. A comprehensive search for original research papers on microbiota composition was conducted using PubMed, Embase, and Scopus databases. Research intestinal permeability, nasal oral microbiomes, interventional were excluded. The yielded results categorized into four groups: vs. healthy controls; severity; non-motor symptoms; clinical phenotypes. review accordance with PRISMA 2020 statement. total 51 met eligibility criteria. In controls group, 22 bacteria deemed potentially important. severity category, two distinguished. symptoms phenotypes categories, no distinct pathogen identified. this report varying taxonomic levels, which prevents authors from reaching a clear conclusion. Future should follow unified methodology order potential

Language: Английский

---

Lipids and the hallmarks of ageing: From pathology to interventions

Mechanisms of Ageing and Development, Journal Year: 2023, Volume and Issue: 215, P. 111858 - 111858

Published: Aug. 29, 2023

Language: Английский

---