Microbiota-microglia crosstalk between Blautia producta and neuroinflammation of Parkinson's disease: A bench-to-bedside translational approach

Brain Behavior and Immunity, Journal Year: 2024, Volume and Issue: 117, P. 270 - 282

Published: Jan. 9, 2024

Parkinson's disease (PD) is intricately linked to abnormal gut microbiota, yet the specific microbiota influencing clinical outcomes remain poorly understood. Our study identified a deficiency in genus Blautia and reduction fecal short-chain fatty acid (SCFA) butyrate level PD patients compared healthy controls. The abundance of correlated with severity PD. Supplementation butyrate-producing bacterium B. producta demonstrated neuroprotective effects, attenuating neuroinflammation dopaminergic neuronal death mice, consequently ameliorating motor dysfunction. A pivotal inflammatory signaling pathway, RAS-related modulated by butyrate, emerged as key mechanism inhibiting microglial activation change RAS-NF-κB pathway was observed. Furthermore, producta-derived inhibition through regulation pathway. These findings elucidate causal relationship between PD, presenting novel microbiota-based treatment perspective for

Language: Английский

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Comprehensive blood metabolomics profiling of Parkinson’s disease reveals coordinated alterations in xanthine metabolism

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

Published: March 19, 2024

Abstract Parkinson’s disease (PD) is a highly heterogeneous disorder influenced by several environmental and genetic factors. Effective disease-modifying therapies robust early-stage biomarkers are still lacking, an improved understanding of the molecular changes in PD could help to reveal new diagnostic markers pharmaceutical targets. Here, we report results from cohort-wide blood plasma metabolic profiling patients controls Luxembourg Study detect disease-associated alterations at level systemic cellular process network alterations. We identified statistically significant both individual metabolite levels global pathway activities vs. correlations with motor impairment scores. As primary observation when investigating shared sub-network alterations, pronounced coordinated increased abundances xanthine metabolism de novo patients, which consistent previous case/control transcriptomics data independent cohort terms known enzyme-metabolite relationships. From integrated metabolomics analysis, enzyme hypoxanthine phosphoribosyltransferase 1 (HPRT1) determined as potential key regulator controlling linking them mechanism that may contribute pathological loss adenosine triphosphate (ATP) PD. Overall, investigations revealed PD-associated metabolome including mechanistically congruent observed data. The HPRT1 merit further investigation main these therapeutic target address downstream pathology

Language: Английский

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Gut Microbiota-Based Interventions for Parkinson’s Disease: Neuroprotective Mechanisms and Current Perspective

Probiotics and Antimicrobial Proteins, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 15, 2025

Language: Английский

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Relationship Between Short-chain Fatty Acids and Parkinson’s Disease: A Review from Pathology to Clinic

Neuroscience Bulletin, Journal Year: 2023, Volume and Issue: 40(4), P. 500 - 516

Published: Sept. 27, 2023

Parkinson's disease (PD) is a complicated neurodegenerative disease, characterized by the accumulation of α-synuclein (α-syn) in Lewy bodies and neurites, massive loss midbrain dopamine neurons. Increasing evidence suggests that gut microbiota microbial metabolites are involved development PD. Among these, short-chain fatty acids (SCFAs), most abundant metabolites, have been proven to play key role brain-gut communication. In this review, we analyze SCFAs pathology PD from multiple dimensions summarize alterations patients as well their correlation with motor non-motor symptoms. Future research should focus on further elucidating neuroinflammation, developing novel strategies employing derivatives treat

Language: Английский

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Gastrointestinal disorders in Parkinson’s disease and other Lewy body diseases

npj Parkinson s Disease, Journal Year: 2023, Volume and Issue: 9(1)

Published: May 5, 2023

Abstract Parkinson’s disease (PD) is pathologically characterized by the abnormal accumulation of α-synuclein fibrils (Lewy bodies) in substantia nigra and other brain regions, although role Lewy bodies remains elusive. Constipation usually precedes motor symptoms PD, which accordance with notion that start from intestinal neural plexus ascend to at least half PD patients. The gut microbiota likely be involved pathologies. Analyses rapid-eye-movement sleep behavior disorder, dementia suggest three pathological pathways. First, Akkermansia , increased degrades mucus layer increases permeability, triggers inflammation oxidative stress plexus. Second, decreased short-chain fatty acids (SCFAs)-producing bacteria reduce number regulatory T cells. Third, SCFAs also aggravate microglial activation an unelucidated pathway. In addition, (DLB), another form α-synucleinopathies, genera, Ruminococcus torques Collinsella may mitigate neuroinflammation increasing secondary bile acids. Interventions for their metabolites potentially delay or development progression body diseases.

Language: Английский

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Blueberry and Blackberry Anthocyanins Ameliorate Metabolic Syndrome by Modulating Gut Microbiota and Short-Chain Fatty Acids Metabolism in High-Fat Diet-Fed C57BL/6J Mice

Journal of Agricultural and Food Chemistry, Journal Year: 2023, Volume and Issue: 71(40), P. 14649 - 14665

Published: Sept. 27, 2023

In this study, blueberry (Vaccinium ssp.) anthocyanins (VA) and blackberry (Rubus L.) (RA) were used to investigate the effects on metabolic syndrome (MetS) potential mechanisms. Importantly, all of data presented in study obtained from experiments conducted mice. As a result, VA RA reduced body weight gain fat accumulation while improving liver damage, inflammation, glucose, lipid metabolism induced by high-fat diet. Moreover, regulated gut microbiota composition, decreasing pro-obesity proinflammation bacteria taxa, such as phylum Actinobacterium genera Allobaculum Bifidobacterium, increasing those negatively associated with obesity Bacteroidetes Prevotella Oscillospira. Additionally, supplementation reversed elevated levels valeric, caproic, isovaleric acids observed diet (HFD) group, bringing them closer Chow group. This reversal indicated that alterations composition abundance may contribute restoration short-chain fatty (SCFAs) levels. PICRUSt2 exhibited cyanamino acid betalain biosynthesis might be major pathways HVA group compared HFD HRA it was phosphotransferase system. These findings suggest can ameliorate MetS modulating production SCFAs.

Language: Английский

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Butyrate as a potential therapeutic agent for neurodegenerative disorders

Neurochemistry International, Journal Year: 2024, Volume and Issue: 176, P. 105745 - 105745

Published: April 18, 2024

Language: Английский

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Prophylactic Administration of Gut Microbiome Metabolites Abrogated Microglial Activation and Subsequent Neuroinflammation in an Experimental Model of Japanese Encephalitis

ACS Chemical Neuroscience, Journal Year: 2024, Volume and Issue: 15(8), P. 1712 - 1727

Published: April 6, 2024

Short-chain fatty acids (SCFAs) are gut microbial metabolic derivatives produced during the fermentation of ingested complex carbohydrates. SCFAs have been widely regarded to a potent anti-inflammatory and neuro-protective role implications in several disease conditions, such as, inflammatory bowel disease, type-2 diabetes, neurodegenerative disorders. Japanese encephalitis virus (JEV), neurotropic flavivirus, is associated with life threatening neuro-inflammation neurological sequelae infected hosts. In this study, we hypothesize that potential mitigating JEV pathogenesis. Postnatal day 10 BALB/c mice were intraperitoneally injected either SCFA mixture (acetate, propionate, butyrate) or PBS for period 7 days, followed by infection. All observed onset progression symptoms. The brain tissue was collected upon reaching terminal illness further analysis. SCFA-supplemented JEV-infected (SCFA + JEV) showed delayed symptoms, lower hindlimb clasping score, decreased weight loss increased survival 3 days (p < 0.0001) infection as opposed PBS-treated animals (JEV). Significant downregulation cytokines TNF-α, MCP-1, IL-6, IFN-Υ group relative control observed. Inflammatory mediators, phospho-NF-kB (P-NF-kB) iba1, 2.08 ± 0.1 3.132 0.43-fold upregulation versus 1.19 0.11 1.31 0.11-fold group, respectively. Tissue section analysis exhibited reduced glial activation (JEV group─42 2.15 microglia/ROI; group─27.07 1.8 microglia/ROI) received supplementation prior seen from astrocytic microglial morphometric Caspase-3 immunoblotting 4.08 1.3-fold compared 1.03 0.14-fold TUNEL assay cellular death post-JEV (JEV-6.4 1.5 cells/ROI JEV-3.7 0.73 cells/ROI). Our study critically contributes increasing evidence support an agent, expand its scope supplementary intervention JEV-mediated neuroinflammation.

Language: Английский

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The Intricate Interplay: Microbial Metabolites and the Gut‐Liver‐Brain Axis in Parkinson's Disease

Journal of Neuroscience Research, Journal Year: 2025, Volume and Issue: 103(1)

Published: Jan. 1, 2025

Parkinson's Disease (PD) is a neurodegenerative disorder marked by the depletion of dopaminergic neurons. Recent studies highlight gut-liver-brain (GLB) axis and its role in PD pathogenesis. The GLB forms dynamic network facilitating bidirectional communication between gastrointestinal tract, liver, central nervous system. Dysregulation within this axis, encompassing gut dysbiosis microbial metabolites, emerging as critical factor influencing progression. Our understanding was traditionally centered on processes brain. However, examining through lens provides new insights. This review comprehensive analysis such short-chain fatty acids (SCFAs), trimethylamine-N-oxide (TMAO), kynurenine, serotonin, bile acids, indoles, dopamine, which are integral to pathogenesis modulation axis. extensive research included literature database searches utilizing resources gutMGene gutMDisorder. These databases have been instrumental identifying specific microbes their shedding light intricate relationship PD. consolidates existing knowledge underscores potential for targeted therapeutic interventions based components, offer avenues future treatment strategies. While not novel concept, first focus specifically PD, highlighting importance integrating liver metabolites players puzzle.

Language: Английский

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Effects of Short Chain Fatty Acid‐Butyrate Supplementation on the Disease Severity, Inflammation, and Psychological Factors in Patients With Active Ulcerative Colitis: A Double‐Blind Randomized Controlled Trial

Journal of Nutrition and Metabolism, Journal Year: 2025, Volume and Issue: 2025(1)

Published: Jan. 1, 2025

Background: Depression and anxiety are common in UC patients due to gut microbiota dysbiosis increased proinflammatory markers. Butyrate, a short-chain fatty acid, participates the regulation of inflammation has neuroprotective effects neurodegenerative disease. Therefore, we assessed sodium butyrate supplementation on disease severity, inflammation, psychological factors active patients. Methods: This study was randomized, parallel, double-blind controlled trial. Participants intervention (n = 18) control groups received 600 mg/kg or rice starch as placebo with their main meal, respectively, for 12 weeks. The partial Mayo score used evaluate while Westergren method employed assess erythrocyte sedimentation rate (ESR). NLR PLR were determined using an automated analyzer (XS-500i, Sysmex). Moreover, by hospital depression scale (HADS) general health questionnaire (GHQ). Results: In comparison placebo, sodium-butyrate significantly decreased ESR level (-6.66 ± 1.56 vs. 3.00 2.11, p=0.01), (-0.24 0.1 0.33 0.23, p=0.02), (-2.33 0.41 0.22 0.40, p < 0.001), HADS (-2.77 0.64 0.94 0.63, p=0.001), (-2.38 0.47 0.61 0.33, GHQ total (-12.11 1.48 3.55 1.39, 0.001). Conclusion: Butyrate could serve effective adjuvant treatment reducing severity alleviating symptoms. trial registered Research Ethics Committee Shiraz University Medical Sciences, reference number IR.SUMS.SCHEANUT.REC.1400.037. Trial Registration: Iranian Registry Clinical Trials: IRCT20211214053401N1.

Language: Английский

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