Safety and efficacy of faecal microbiota transplantation in patients with mild to moderate Parkinson's disease (GUT-PARFECT): a double-blind, placebo-controlled, randomised, phase 2 trial DOI Creative Commons
Arnout Bruggeman, Charysse Vandendriessche, Hannelore Hamerlinck

et al.

EClinicalMedicine, Journal Year: 2024, Volume and Issue: 71, P. 102563 - 102563

Published: March 27, 2024

BackgroundDysregulation of the gut microbiome has been implicated in Parkinson's disease (PD). This study aimed to evaluate clinical effects and safety a single faecal microbiota transplantation (FMT) patients with early-stage PD.MethodsThe GUT-PARFECT trial, single-centre randomised, double-blind, placebo-controlled trial was conducted at Ghent University Hospital between December 01, 2020 12, 2022. Participants (aged 50–65 years, Hoehn Yahr stage 2) were randomly assigned receive nasojejunal FMT either healthy donor stool or their own stool. Computer-generated randomisation done 1:1 ratio through permutated-block scheduling. Treatment allocation concealed for participants investigators. The primary outcome measure 12 months change Movement Disorders Society-Unified Disease Rating Scale (MDS-UPDRS) motor score obtained during off-medication evaluations. Intention-to-treat analysis performed using mixed model repeated measures analysis. completed is registered on ClinicalTrials.gov (NCT03808389).FindingsBetween 2021, procedures 46 PD: 22 group 24 placebo group. Clinical evaluations baseline, 3, 6, post-FMT. Full data possible 21 After months, MDS-UPDRS significantly improved by mean 5.8 points (95% CI −11.4 −0.2) 2.7 (−8.3 2.9) (p = 0.0235). Adverse events limited temporary abdominal discomfort.InterpretationOur findings suggested induced mild, but long-lasting beneficial symptoms PD. These highlight potential modulating as therapeutic approach warrant further exploration larger cohorts PD various stages.FundingFlemish patient organizations (VPL Parkili), Research Foundation Flanders (FWO), Biocodex Microbiota Foundation.

Language: Английский

Inflammation and immune dysfunction in Parkinson disease DOI Open Access
Malú G. Tansey, Rebecca L. Wallings, Madelyn C. Houser

et al.

Nature reviews. Immunology, Journal Year: 2022, Volume and Issue: 22(11), P. 657 - 673

Published: March 4, 2022

Language: Английский

Citations

789
Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases DOI Creative Commons
Jian Sheng Loh, Wen Qi Mak, Li Tan

et al.

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
Short-chain fatty acids: linking diet, the microbiome and immunity DOI
Elizabeth R. Mann, Ying Ka Lam, Holm H. Uhlig

et al.

Nature reviews. Immunology, Journal Year: 2024, Volume and Issue: 24(8), P. 577 - 595

Published: April 2, 2024

Language: Английский

Citations

230
The microbiome–gut–brain axis in Parkinson disease — from basic research to the clinic DOI
Ai Huey Tan, Shen‐Yang Lim, Anthony E. Lang

et al.

Nature Reviews Neurology, Journal Year: 2022, Volume and Issue: 18(8), P. 476 - 495

Published: June 24, 2022

Language: Английский

Citations

209
Short-chain fatty acids in diseases DOI Creative Commons
Dan Zhang,

Yong‐Ping Jian,

Yuning Zhang

et al.

Cell Communication and Signaling, Journal Year: 2023, Volume and Issue: 21(1)

Published: Aug. 18, 2023

Abstract Short-chain fatty acids (SCFAs) are the main metabolites produced by bacterial fermentation of dietary fibre in gastrointestinal tract. The absorption SCFAs is mediated substrate transporters, such as monocarboxylate transporter 1 and sodium-coupled 1, which promote cellular metabolism. An increasing number studies have implicated microorganisms crucial executors diet-based microbial influence on host. important fuels for intestinal epithelial cells (IECs) represent a major carbon flux from diet, that decomposed gut microbiota. play vital role multiple molecular biological processes, promoting secretion glucagon-like peptide-1 IECs to inhibit elevation blood glucose, expression G protein-coupled receptors GPR41 GPR43, inhibiting histone deacetylases, participate regulation proliferation, differentiation, function IECs. affect motility, barrier function, host Furthermore, regulatory roles local, intermediate, peripheral metabolisms. Acetate, propionate, butyrate SCFAs, they involved immunity, apoptosis, inflammation, lipid Herein, we review diverse functional this class reflect their ability intestine, metabolic, other diseases.

Language: Английский

Citations

196
Association of Fecal and Plasma Levels of Short-Chain Fatty Acids With Gut Microbiota and Clinical Severity in Patients With Parkinson Disease DOI Creative Commons

Szu‐Ju Chen,

Chieh‐Chang Chen,

Hsin-Yu Liao

et al.

Neurology, Journal Year: 2022, Volume and Issue: 98(8)

Published: Jan. 7, 2022

Background and Objectives

Short-chain fatty acids (SCFAs) are gut microbial metabolites that promote the disease process in a rodent model of Parkinson (PD), but fecal levels SCFAs patients with PD reduced. Simultaneous assessments plasma SCFA levels, their interrelationships process, scarce. We aimed to compare different subtypes healthy controls delineate interrelations link microbiota changes clinical severity PD.

Methods

A cohort 96 85 were recruited from National Taiwan University Hospital. Fecal concentrations measured using chromatography mass spectrometry. Gut was analyzed metagenomic shotgun sequencing. Body index medical comorbidities evaluated dietary information obtained food frequency questionnaire. To assess motor cognitive impairment, we used Movement Disorder Society–Unified Parkinson9s Disease Rating Scale (MDS-UPDRS) Mini-Mental Status Examination (MMSE).

Results

Compared controls, had lower higher acetate, propionate, butyrate. After adjustment for age, sex, duration, anti-PD medication dosage, MDS-UPDRS part III scores correlated reduced acetate (ρ = −0.37, p 0.012), propionate −0.32, 0.036), butyrate −0.40, 0.004) increased 0.26, 0.042) MMSE negatively −0.09, 0.027) valerate −0.032, 0.033) after confounders. SCFAs-producing bacteria positively revealed no association In patient group, abundance proinflammatory microbes, such as Clostridiales bacterium NK3B98 Ruminococcus sp AM07-15, significantly decreased SCFAs, especially propionic acid.

Discussion

Reductions observed corelated specific

Classification Evidence

This study provides Class evidence metabolite distinguish between associated

Language: Английский

Citations

169
The gut microbiome in Alzheimer’s disease: what we know and what remains to be explored DOI Creative Commons
Sidhanth Chandra, Sangram S. Sisodia, Robert Vassar

et al.

Molecular Neurodegeneration, Journal Year: 2023, Volume and Issue: 18(1)

Published: Feb. 1, 2023

Alzheimer's disease (AD), the most common cause of dementia, results in a sustained decline cognition. There are currently few effective modifying therapies for AD, but insights into mechanisms that mediate onset and progression may lead to new, therapeutic strategies. Amyloid beta oligomers plaques, tau aggregates, neuroinflammation play critical role neurodegeneration impact clinical AD progression. The upstream modulators these pathological features have not been fully clarified, recent evidence indicates gut microbiome (GMB) an influence on therefore human patients. In this review, we summarize studies identified alterations GMB correlate with pathophysiology patients mouse models. Additionally, discuss findings manipulations models potential GMB-targeted therapeutics AD. Lastly, diet, sleep, exercise as modifiers relationship between conclude future directions recommendations further topic.

Language: Английский

Citations

154
The intestinal barrier in disorders of the central nervous system DOI
Carolina Pellegrini, Matteo Fornai, Vanessa D’Antongiovanni

et al.

˜The œLancet. Gastroenterology & hepatology, Journal Year: 2022, Volume and Issue: 8(1), P. 66 - 80

Published: Nov. 2, 2022

Language: Английский

Citations

115
Gut Microbiota: A Novel Therapeutic Target for Parkinson’s Disease DOI Creative Commons

Manlian Zhu,

Xia Liu, Yiru Ye

et al.

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

Citations

107
The gut vascular barrier: a new player in the gut–liver–brain axis DOI Open Access
Paola Brescia, María Rescigno

Trends in Molecular Medicine, Journal Year: 2021, Volume and Issue: 27(9), P. 844 - 855

Published: July 3, 2021

Language: Английский

Citations

106