{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T11:42:52Z","timestamp":1787226172528,"version":"build-2736575974"},"reference-count":97,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,1,18]],"date-time":"2023-01-18T00:00:00Z","timestamp":1674000000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging Neurosci."],"abstract":"<jats:p>An increasing number of studies in recent years have focused on the role that the gut may play in Parkinson\u2019s Disease (PD) pathogenesis, suggesting that the maintenance of a healthy gut may lead to potential treatments of the disease. The health of microbiota has been shown to be directly associated with parameters that play a potential role in PD including gut barrier integrity, immunity, function, metabolism and the correct functioning of the gut-brain axis. The gut microbiota (GM) may therefore be employed as valuable indicators for early diagnosis of PD and potential targets for preventing or treating PD symptoms. Preserving the gut homeostasis using probiotics may therefore lead to a promising treatment strategy due to their known benefits in improving constipation, motor impairments, inflammation, and neurodegeneration. However, the mechanisms underlying the effects of probiotics in PD are yet to be clarified. In this project, we have tested the efficacy of an oral probiotic suspension, Symprove\u2122, on an established animal model of PD. Symprove\u2122, unlike many commercially available probiotics, has been shown to be resistant to gastric acidity, improve symptoms in gastrointestinal diseases and improve gut integrity in an <jats:italic>in vitro<\/jats:italic> PD model. In this study, we used an early-stage PD rat model to determine the effect of Symprove\u2122 on neurodegeneration and neuroinflammation in the brain and on plasma cytokine levels, GM composition and short chain fatty acid (SCFA) release. Symprove\u2122 was shown to significantly influence both the gut and brain of the PD model. It preserved the gut integrity in the PD model, reduced plasma inflammatory markers and changed microbiota composition. The treatment also prevented the reduction in SCFAs and striatal inflammation and prevented tyrosine hydroxylase (TH)-positive cell loss by 17% compared to that observed in animals treated with placebo. We conclude that Symprove\u2122 treatment may have a positive influence on the symptomology of early-stage PD with obvious implications for the improvement of gut integrity and possibly delaying\/preventing the onset of neuroinflammation and neurodegeneration in human PD patients.<\/jats:p>","DOI":"10.3389\/fnagi.2022.986127","type":"journal-article","created":{"date-parts":[[2023,1,18]],"date-time":"2023-01-18T07:45:32Z","timestamp":1674027932000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":19,"title":["Effects of a probiotic suspension Symprove\u2122 on a rat early-stage Parkinson\u2019s disease model"],"prefix":"10.3389","volume":"14","author":[{"given":"Marco","family":"Sancandi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"De Caro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neringa","family":"Cypaite","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadia","family":"Marascio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Avagliano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmela","family":"De Marco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilio","family":"Russo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Constanti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Audrey","family":"Mercer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,1,18]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1186\/s13024-021-00427-6","article-title":"Relationships of gut microbiota, short-chain fatty acids, inflammation, and the gut barrier in Parkinson\u2019s disease","volume":"16","author":"Aho","year":"2021","journal-title":"Mol. Neurodegener."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1007\/s11910-022-01207-5","article-title":"Neurodegeneration and neuroinflammation in Parkinson\u2019s disease: a self-sustained loop","volume":"22","author":"Arena","year":"2022","journal-title":"Curr. Neurol. Neurosci. Rep."},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02095-16","article-title":"Robust central nervous system pathology in transgenic mice following peripheral injection of alpha-synuclein fibrils","author":"Ayers","year":"2017","journal-title":"J. Virol."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1016\/j.parkreldis.2008.07.004","article-title":"Dopamine agonists in the treatment of early Parkinson's disease: a meta-analysis","volume":"15","author":"Baker","year":"2009","journal-title":"Parkinsonism Relat. Disord."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"1274","DOI":"10.1212\/WNL.0000000000003127","article-title":"Probiotics and prebiotic fiber for constipation associated with Parkinson disease: an RCT","volume":"87","author":"Barichella","year":"2016","journal-title":"Neurology"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1007\/s10787-019-00595-4","article-title":"A randomised, double-blind, placebo-controlled trial of a multi-strain probiotic in patients with asymptomatic ulcerative colitis and Crohn\u2019s disease","volume":"27","author":"Bjarnason","year":"2019","journal-title":"Inflammopharmacology"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"S281","DOI":"10.3233\/JPD-191721","article-title":"Brain-first versus gut-first Parkinson's disease: a hypothesis","volume":"9","author":"Borghammer","year":"2019","journal-title":"J. Parkinsons Dis."},{"key":"ref8","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1016\/s0197-4580(02)00065-9","article-title":"Staging of brain pathology related to sporadic Parkinson\u2019s disease","volume":"24","author":"Braak","year":"2003","journal-title":"Neurobiol. Aging"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"9182","DOI":"10.1128\/JVI.01399-16","article-title":"Neuroinvasion of alpha-synuclein prionoids after intraperitoneal and intraglossal inoculation","volume":"90","author":"Breid","year":"2016","journal-title":"J. Virol."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"581","DOI":"10.1038\/nmeth.3869","article-title":"DADA2: high-resolution sample inference from illumina amplicon data","volume":"13","author":"Callahan","year":"2016","journal-title":"Nat. Methods"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1038\/s41531-021-00191-w","article-title":"Early constipation predicts faster dementia onset in Parkinson's disease","volume":"7","author":"Camacho","year":"2021","journal-title":"NPJ Parkinsons Dis."},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22126242","article-title":"Interaction between lipopolysaccharide and gut microbiota in inflammatory bowel diseases","volume":"22","author":"Candelli","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"ref01","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1038\/nmeth.f.303","article-title":"QIIME allows analysis of high-throughput community sequencing data","volume":"7","author":"Caporaso","year":"2010","journal-title":"Nat Methods"},{"key":"ref13","first-page":"117","article-title":"Use of probiotics for the treatment of constipation in Parkinson\u2019s disease patients","volume":"57","author":"Cassani","year":"2011","journal-title":"Minerva Gastroenterol. Dietol."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"628","DOI":"10.4103\/1673-5374.295270","article-title":"The emerging role of probiotics in neurodegenerative diseases: new hope for Parkinson\u2019s disease?","volume":"16","author":"Castelli","year":"2021","journal-title":"Neural Regen. Res."},{"key":"ref15","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1016\/j.brainres.2018.01.011","article-title":"Enteric nervous system manifestations of neurodegenerative disease","volume":"1693","author":"Chalazonitis","year":"2018","journal-title":"Brain Res."},{"key":"ref16","doi-asserted-by":"publisher","first-page":"1129","DOI":"10.3233\/JPD-212574","article-title":"Plasma lipopolysaccharide-binding protein reflects risk and progression of Parkinson\u2019s disease","volume":"11","author":"Chen","year":"2021","journal-title":"J. Parkinsons Dis."},{"key":"ref17","doi-asserted-by":"publisher","first-page":"e0217194","DOI":"10.1371\/journal.pone.0217194","article-title":"High-throughput 16S rRNA gene sequencing reveals that 6-hydroxydopamine affects gut microbial environment","volume":"14","author":"Choi","year":"2019","journal-title":"PLoS One"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"991","DOI":"10.1046\/j.1460-9568.2002.01938.x","article-title":"Neuroinflammation of the nigrostriatal pathway during progressive 6-OHDA dopamine degeneration in rats monitored by immunohistochemistry and PET imaging","volume":"15","author":"Cicchetti","year":"2002","journal-title":"Eur. J. Neurosci."},{"key":"ref19","doi-asserted-by":"publisher","first-page":"529","DOI":"10.1111\/epi.16813","article-title":"First evidence of altered microbiota and intestinal damage and their link to absence epilepsy in a genetic animal model, the WAG\/Rij rat","volume":"62","author":"Citraro","year":"2021","journal-title":"Epilepsia"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1007\/978-1-4939-9124-2_4","article-title":"Detection of misfolded alpha-synuclein aggregates in cerebrospinal fluid by the protein misfolding cyclic amplification platform","volume":"1948","author":"Concha-Marambio","year":"2019","journal-title":"Methods Mol. Biol."},{"key":"ref21","doi-asserted-by":"publisher","first-page":"938","DOI":"10.1126\/science.abo4442","article-title":"Microbiota-brain axis: context and causality","volume":"376","author":"Cryan","year":"2022","journal-title":"Science"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"620221","DOI":"10.3389\/fphar.2020.620221","article-title":"Analgesic and anti-inflammatory effects of perampanel in acute and chronic pain models in mice: interaction with the cannabinergic system","volume":"11","author":"De Caro","year":"2020","journal-title":"Front. Pharmacol."},{"key":"ref23","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1111\/j.1432-0436.1984.tb01355.x","article-title":"Monoclonal antibodies specific for glial fibrillary acidic (GFA) protein and for each of the neurofilament triplet polypeptides","volume":"25","author":"Debus","year":"1983","journal-title":"Differentiation"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1016\/j.brainresbull.2022.02.015","article-title":"Brain-gut-microbiota axis in Parkinson\u2019s disease: a historical review and future perspective","volume":"183","author":"Dong","year":"2022","journal-title":"Brain Res. Bull."},{"key":"ref25","doi-asserted-by":"publisher","first-page":"527","DOI":"10.1016\/j.nbd.2011.10.026","article-title":"Olfaction in Parkinson's disease and related disorders","volume":"46","author":"Doty","year":"2012","journal-title":"Neurobiol. Dis."},{"key":"ref26","doi-asserted-by":"publisher","first-page":"363","DOI":"10.5056\/jnm19044","article-title":"Parkinson's disease: the emerging role of gut dysbiosis, antibiotics, probiotics, and fecal microbiota transplantation","volume":"25","author":"Dutta","year":"2019","journal-title":"J. Neurogastroenterol. Motil."},{"key":"ref27","doi-asserted-by":"publisher","DOI":"10.3791\/58592","article-title":"Biocytin recovery and 3D reconstructions of filled hippocampal CA2 interneurons","volume":"141","author":"Economides","year":"2018","journal-title":"J. Vis. Exp."},{"key":"ref28","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1016\/j.neulet.2010.01.033","article-title":"Low-grade endotoxemia in patients with severe autism","volume":"471","author":"Emanuele","year":"2010","journal-title":"Neurosci. Lett."},{"key":"ref29","doi-asserted-by":"publisher","first-page":"e28032","DOI":"10.1371\/journal.pone.0028032","article-title":"Increased intestinal permeability correlates with sigmoid mucosa alpha-synuclein staining and endotoxin exposure markers in early Parkinson's disease","volume":"6","author":"Forsyth","year":"2011","journal-title":"PLoS One"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"141","DOI":"10.3920\/BM2014.0051","article-title":"Comparative survival of commercial probiotic formulations: tests in biorelevant gastric fluids and real-time measurements using microcalorimetry","volume":"6","author":"Fredua-Agyeman","year":"2015","journal-title":"Benef. Microbes"},{"key":"ref31","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20174121","article-title":"Probiotics for Parkinson's disease","volume":"20","author":"Gazerani","year":"2019","journal-title":"Int. J. Mol. Sci."},{"key":"ref32","doi-asserted-by":"publisher","first-page":"100087","DOI":"10.1016\/j.ijpx.2021.100087","article-title":"Influence of probiotic bacteria on gut microbiota composition and gut wall function in an in-vitro model in patients with Parkinson's disease","volume":"3","author":"Ghyselinck","year":"2021","journal-title":"Int. J. Pharm. X"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"119648","DOI":"10.1016\/j.ijpharm.2020.119648","article-title":"A 4-strain probiotic supplement influences gut microbiota composition and gut wall function in patients with ulcerative colitis","volume":"587","author":"Ghyselinck","year":"2020","journal-title":"Int. J. Pharm."},{"key":"ref34","doi-asserted-by":"publisher","first-page":"111376","DOI":"10.1016\/j.exger.2021.111376","article-title":"Neuroprotective effects of short-chain fatty acids in MPTP induced mice model of Parkinson's disease","volume":"150","author":"Hou","year":"2021","journal-title":"Exp. Gerontol."},{"key":"ref35","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1186\/s40168-020-00988-6","article-title":"Gut microbiota-derived propionate mediates the neuroprotective effect of osteocalcin in a mouse model of Parkinson's disease","volume":"9","author":"Hou","year":"2021","journal-title":"Microbiome"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"793","DOI":"10.1002\/mds.27326","article-title":"Stool immune profiles evince gastrointestinal inflammation in Parkinson\u2019s disease","volume":"33","author":"Houser","year":"2018","journal-title":"Mov. Disord."},{"key":"ref37","doi-asserted-by":"publisher","DOI":"10.3390\/brainsci10040206","article-title":"Probiotics alleviate the progressive deterioration of motor functions in a mouse model of Parkinson\u2019s disease","volume":"10","author":"Hsieh","year":"2020","journal-title":"Brain Sci."},{"key":"ref38","doi-asserted-by":"publisher","first-page":"855","DOI":"10.1006\/bbrc.1996.1112","article-title":"A novel gene Iba 1 in the major histocompatibility complex class III region encoding an EF hand protein expressed in a monocytic lineage","volume":"224","author":"Imai","year":"1996","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref39","doi-asserted-by":"publisher","first-page":"1560","DOI":"10.1177\/0963689717721234","article-title":"A new treatment strategy for Parkinson's disease through the gut-brain axis: the glucagon-like peptide-1 receptor pathway","volume":"26","author":"Kim","year":"2017","journal-title":"Cell Transplant."},{"key":"ref40","doi-asserted-by":"publisher","first-page":"728","DOI":"10.1038\/nri3312","article-title":"The impact of probiotics and prebiotics on the immune system","volume":"12","author":"Klaenhammer","year":"2012","journal-title":"Nat. Rev. Immunol."},{"key":"ref41","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1002\/mds.26866","article-title":"Constipation in parkinson's disease: subjective symptoms, objective markers, and new perspectives","volume":"32","author":"Knudsen","year":"2017","journal-title":"Mov. Disord."},{"key":"ref42","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1007\/s10787-017-0363-y","article-title":"A randomized double-blind placebo-controlled trial of a multi-strain probiotic in treatment of symptomatic uncomplicated diverticular disease","volume":"25","author":"Kvasnovsky","year":"2017","journal-title":"Inflammopharmacology"},{"key":"ref43","doi-asserted-by":"publisher","first-page":"2004","DOI":"10.1007\/s13311-020-00893-8","article-title":"IL-6 receptor blockade by tocilizumab has anti-absence and anti-epileptogenic effects in the WAG\/Rij rat model of absence epilepsy","volume":"17","author":"Leo","year":"2020","journal-title":"Neurotherapeutics"},{"key":"ref44","doi-asserted-by":"publisher","first-page":"103908","DOI":"10.1016\/j.ebiom.2022.103908","article-title":"Microbiota and the gut-brain-axis: implications for new therapeutic design in the CNS","volume":"77","author":"Liu","year":"2022","journal-title":"EBioMedicine"},{"key":"ref45","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1038\/s41531-020-00145-8","article-title":"Irritable bowel syndrome and Parkinson's disease risk: register-based studies","volume":"7","author":"Liu","year":"2021","journal-title":"NPJ Parkinsons Dis."},{"key":"ref46","doi-asserted-by":"publisher","first-page":"515","DOI":"10.1007\/s00401-019-02037-5","article-title":"Oral and intravenous transmission of alpha-synuclein fibrils to mice","volume":"138","author":"Lohmann","year":"2019","journal-title":"Acta Neuropathol."},{"key":"ref47","doi-asserted-by":"publisher","first-page":"1377","DOI":"10.1007\/s00415-020-09723-5","article-title":"Gastrointestinal dysfunction in Parkinson\u2019s disease","volume":"267","author":"Lubomski","year":"","journal-title":"J. Neurol."},{"key":"ref48","doi-asserted-by":"publisher","first-page":"2507","DOI":"10.1007\/s00415-019-09320-1","article-title":"Parkinson\u2019s disease and the gastrointestinal microbiome","volume":"267","author":"Lubomski","year":"","journal-title":"J. Neurol."},{"key":"ref49","doi-asserted-by":"publisher","first-page":"780","DOI":"10.1007\/s00415-021-10657-9","article-title":"The impact of device-assisted therapies on the gut microbiome in Parkinson\u2019s disease","volume":"269","author":"Lubomski","year":"2022","journal-title":"J. Neurol."},{"key":"ref50","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1038\/s41531-022-00357-0","article-title":"Opportunities and challenges of alpha-synuclein as a potential biomarker for Parkinson\u2019s disease and other synucleinopathies","volume":"8","author":"Magalhaes","year":"2022","journal-title":"NPJ Parkinsons Dis."},{"key":"ref51","doi-asserted-by":"publisher","first-page":"694","DOI":"10.1007\/s10620-020-06244-z","article-title":"Efficacy of single-strain probiotics versus multi-strain mixtures: systematic review of strain and disease specificity","volume":"66","author":"McFarland","year":"2021","journal-title":"Dig. Dis. Sci."},{"key":"ref52","doi-asserted-by":"publisher","first-page":"1154","DOI":"10.1007\/s00415-021-10567-w","article-title":"Gastrointestinal dysfunction in Parkinson's disease: molecular pathology and implications of gut microbiome, probiotics, and fecal microbiota transplantation","volume":"269","author":"Metta","year":"2022","journal-title":"J. Neurol."},{"key":"ref53","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.ijpharm.2018.11.020","article-title":"A four-strain probiotic exerts positive immunomodulatory effects by enhancing colonic butyrate production in vitro","volume":"555","author":"Moens","year":"2019","journal-title":"Int. J. Pharm."},{"key":"ref54","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1038\/s41579-020-00460-0","article-title":"The gut microbiota-brain axis in behaviour and brain disorders","volume":"19","author":"Morais","year":"2021","journal-title":"Nat. Rev. Microbiol."},{"key":"ref55","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1111\/cns.13068","article-title":"Available and future treatments for atypical parkinsonism. A systematic review","volume":"25","author":"Moretti","year":"2019","journal-title":"CNS Neurosci. Ther."},{"key":"ref56","doi-asserted-by":"publisher","first-page":"729","DOI":"10.1111\/j.1348-0421.2000.tb02556.x","article-title":"Upregulated expression of Iba 1 molecules in the central nervous system of mice in response to neurovirulent influenza a virus infection","volume":"44","author":"Mori","year":"2000","journal-title":"Microbiol. Immunol."},{"key":"ref57","doi-asserted-by":"publisher","first-page":"10609","DOI":"10.3748\/wjg.v21.i37.10609","article-title":"Brain-gut-microbiota axis in Parkinson's disease","volume":"21","author":"Mulak","year":"2015","journal-title":"World J. Gastroenterol."},{"key":"ref58","doi-asserted-by":"publisher","first-page":"2897","DOI":"10.3389\/fmicb.2018.02897","article-title":"Comparative microbiome signatures and short-chain fatty acids in mouse, rat, non-human primate, and human feces","volume":"9","author":"Nagpal","year":"2018","journal-title":"Front. Microbiol."},{"key":"ref59","doi-asserted-by":"publisher","first-page":"1332","DOI":"10.4103\/1673-5374.235219","article-title":"Targeting the noradrenergic system for anti-inflammatory and neuroprotective effects: implications for Parkinson's disease","volume":"13","author":"O'Neill","year":"2018","journal-title":"Neural Regen. Res."},{"key":"ref60","doi-asserted-by":"publisher","DOI":"10.3390\/molecules25112502","article-title":"Propionic acid and fasudil as treatment against rotenone toxicity in an in vitro model of Parkinson\u2019s disease","volume":"25","author":"Ostendorf","year":"2020","journal-title":"Molecules"},{"key":"ref61","doi-asserted-by":"publisher","first-page":"306","DOI":"10.3389\/fnins.2015.00306","article-title":"Abnormal lipopolysaccharide binding protein as marker of gastrointestinal inflammation in Parkinson disease","volume":"9","author":"Pal","year":"2015","journal-title":"Front. Neurosci."},{"key":"ref62","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.parkreldis.2017.02.002","article-title":"Gut microbiota: implications in Parkinson\u2019s disease","volume":"38","author":"Parashar","year":"2017","journal-title":"Parkinsonism Relat. Disord."},{"key":"ref63","doi-asserted-by":"publisher","first-page":"987","DOI":"10.1099\/jmm.0.46101-0","article-title":"Differences between the gut microflora of children with autistic spectrum disorders and that of healthy children","volume":"54","author":"Parracho","year":"2005","journal-title":"J. Med. Microbiol."},{"key":"ref64","doi-asserted-by":"publisher","first-page":"1989","DOI":"10.1016\/j.bbagen.2016.06.018","article-title":"L-DOPA-induced hyperhomocysteinemia in Parkinson's disease: elephant in the room","volume":"1860","author":"Paul","year":"2016","journal-title":"Biochim. Biophys. Acta"},{"key":"ref65","doi-asserted-by":"publisher","first-page":"57","DOI":"10.3389\/fnagi.2017.00057","article-title":"Promising effects of neurorestorative diets on motor, cognitive, and gastrointestinal dysfunction after symptom development in a mouse model of Parkinson's disease","volume":"9","author":"Perez-Pardo","year":"","journal-title":"Front. Aging Neurosci."},{"key":"ref66","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1016\/j.ejphar.2017.05.042","article-title":"The gut-brain axis in Parkinson\u2019s disease: possibilities for food-based therapies","volume":"817","author":"Perez-Pardo","year":"","journal-title":"Eur. J. Pharmacol."},{"key":"ref67","doi-asserted-by":"publisher","first-page":"17013","DOI":"10.1038\/nrdp.2017.13","article-title":"Parkinson disease","volume":"3","author":"Poewe","year":"2017","journal-title":"Nat. Rev. Dis. Primers."},{"key":"ref68","doi-asserted-by":"publisher","first-page":"D590","DOI":"10.1093\/nar\/gks1219","article-title":"The SILVA ribosomal RNA gene database project: improved data processing and web-based tools","volume":"41","author":"Quast","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"ref69","doi-asserted-by":"publisher","first-page":"S26","DOI":"10.4103\/0028-3886.226451","article-title":"Parkinson's disease: A review","volume":"66","author":"Radhakrishnan","year":"2018","journal-title":"Neurol. India"},{"key":"ref70","doi-asserted-by":"publisher","first-page":"936","DOI":"10.1038\/gt.2011.157","article-title":"In utero administration of Ad5 and AAV pseudotypes to the fetal brain leads to efficient, widespread and long-term gene expression","volume":"19","author":"Rahim","year":"2012","journal-title":"Gene Ther."},{"key":"ref71","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1038\/s41531-021-00156-z","article-title":"Meta-analysis of the Parkinson's disease gut microbiome suggests alterations linked to intestinal inflammation","volume":"7","author":"Romano","year":"2021","journal-title":"NPJ Parkinsons Dis."},{"key":"ref72","doi-asserted-by":"publisher","first-page":"416","DOI":"10.3389\/fnagi.2018.00416","article-title":"Probiotics and prebiotics as a therapeutic strategy to improve memory in a model of middle-aged rats","volume":"10","author":"Romo-Araiza","year":"2018","journal-title":"Front. Aging Neurosci."},{"key":"ref73","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1016\/j.bbi.2014.06.016","article-title":"Early molecular and behavioral response to lipopolysaccharide in the WAG\/Rij rat model of absence epilepsy and depressive-like behavior, involves interplay between AMPK, AKT\/mTOR pathways and neuroinflammatory cytokine release","volume":"42","author":"Russo","year":"2014","journal-title":"Brain Behav. Immun."},{"key":"ref74","doi-asserted-by":"publisher","first-page":"604179","DOI":"10.3389\/fimmu.2020.604179","article-title":"The gut-brain axis: how microbiota and host inflammasome influence brain physiology and pathology","volume":"11","author":"Rutsch","year":"2020","journal-title":"Front. Immunol."},{"key":"ref75","doi-asserted-by":"publisher","first-page":"3461","DOI":"10.3892\/etm.2019.7943","article-title":"Dysbiosis of Gram-negative gut microbiota and the associated serum lipopolysaccharide exacerbates inflammation in type 2 diabetic patients with chronic kidney disease","volume":"18","author":"Salguero","year":"2019","journal-title":"Exp. Ther. Med."},{"key":"ref76","doi-asserted-by":"publisher","first-page":"479","DOI":"10.3389\/fncel.2018.00479","article-title":"Structural changes observed in the piriform cortex in a rat model of pre-motor Parkinson\u2019s disease","volume":"12","author":"Sancandi","year":"2018","journal-title":"Front. Cell. Neurosci."},{"key":"ref77","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1038\/s41575-019-0173-3","article-title":"Probiotics and prebiotics in intestinal health and disease: from biology to the clinic","volume":"16","author":"Sanders","year":"2019","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref78","doi-asserted-by":"publisher","first-page":"636545","DOI":"10.3389\/fnagi.2021.636545","article-title":"The association between the gut microbiota and Parkinson's disease, a meta-analysis","volume":"13","author":"Shen","year":"2021","journal-title":"Front. Aging Neurosci."},{"key":"ref79","doi-asserted-by":"publisher","first-page":"105380","DOI":"10.1016\/j.neuint.2022.105380","article-title":"Neuroprotective approaches to halt Parkinson's disease progression","volume":"158","author":"Sola","year":"2022","journal-title":"Neurochem. Int."},{"key":"ref80","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1016\/j.jnutbio.2019.03.021","article-title":"Probiotics mixture increases butyrate, and subsequently rescues the nigral dopaminergic neurons from MPTP and rotenone-induced neurotoxicity","volume":"69","author":"Srivastav","year":"2019","journal-title":"J. Nutr. Biochem."},{"key":"ref81","doi-asserted-by":"publisher","first-page":"522","DOI":"10.1002\/ana.24448","article-title":"Vagotomy and subsequent risk of Parkinson's disease","volume":"78","author":"Svensson","year":"2015","journal-title":"Ann. Neurol."},{"key":"ref82","doi-asserted-by":"publisher","first-page":"1031","DOI":"10.1016\/j.clnu.2018.05.018","article-title":"Clinical and metabolic response to probiotic administration in people with Parkinson's disease: a randomized, double-blind, placebo-controlled trial","volume":"38","author":"Tamtaji","year":"2019","journal-title":"Clin. Nutr."},{"key":"ref83","doi-asserted-by":"publisher","first-page":"414","DOI":"10.1002\/jgh3.12450","article-title":"Probiotics for Parkinson's disease: current evidence and future directions","volume":"5","author":"Tan","year":"","journal-title":"JGH Open"},{"key":"ref84","doi-asserted-by":"publisher","first-page":"e772","DOI":"10.1212\/WNL.0000000000010998","article-title":"Probiotics for constipation in Parkinson disease: a randomized placebo-controlled study","volume":"96","author":"Tan","year":"","journal-title":"Neurology"},{"key":"ref85","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23115938","article-title":"An overview of oxidative stress, neuroinflammation, and neurodegenerative diseases","volume":"23","author":"Teleanu","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"ref86","doi-asserted-by":"publisher","first-page":"673","DOI":"10.1038\/s41575-020-0339-z","article-title":"Parkinson disease and the gut: new insights into pathogenesis and clinical relevance","volume":"17","author":"Travagli","year":"2020","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref87","doi-asserted-by":"publisher","DOI":"10.3390\/antiox10111823","article-title":"Probiotic enhancement of antioxidant capacity and alterations of gut microbiota composition in 6-hydroxydopamin-induced Parkinson's disease rats","volume":"10","author":"Tsao","year":"2021","journal-title":"Antioxidants"},{"key":"ref88","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1007\/s00401-019-02040-w","article-title":"Evidence for bidirectional and trans-synaptic parasympathetic and sympathetic propagation of alpha-synuclein in rats","volume":"138","author":"Van Den Berge","year":"2019","journal-title":"Acta Neuropathol."},{"key":"ref89","doi-asserted-by":"publisher","first-page":"1087","DOI":"10.3389\/fneur.2019.01087","article-title":"Contributions of gut bacteria and diet to drug pharmacokinetics in the treatment of Parkinson's disease","volume":"10","author":"van Kessel","year":"2019","journal-title":"Front. Neurol."},{"key":"ref90","doi-asserted-by":"publisher","first-page":"310","DOI":"10.1038\/s41467-019-08294-y","article-title":"Gut bacterial tyrosine decarboxylases restrict levels of levodopa in the treatment of Parkinson's disease","volume":"10","author":"van Kessel","year":"2019","journal-title":"Nat. Commun."},{"key":"ref91","doi-asserted-by":"publisher","first-page":"2571","DOI":"10.1093\/brain\/awab156","article-title":"The role of gut dysbiosis in Parkinson's disease: mechanistic insights and therapeutic options","volume":"144","author":"Wang","year":"2021","journal-title":"Brain"},{"key":"ref92","doi-asserted-by":"publisher","first-page":"1491","DOI":"10.3233\/JPD-212707","article-title":"Parkinson's disease and the gut: symptoms, nutrition, and microbiota","volume":"11","author":"Yemula","year":"2021","journal-title":"J. Parkinsons Dis."},{"key":"ref93","doi-asserted-by":"publisher","first-page":"567","DOI":"10.1038\/s41598-017-16790-8","article-title":"Parkinson disease with constipation: clinical features and relevant factors","volume":"8","author":"Yu","year":"2018","journal-title":"Sci. Rep."},{"key":"ref94","doi-asserted-by":"publisher","first-page":"1064","DOI":"10.3389\/fimmu.2017.01064","article-title":"Microbiome-derived lipopolysaccharide enriched in the perinuclear region of Alzheimer\u2019s disease brain","volume":"8","author":"Zhao","year":"2017","journal-title":"Front. Immunol."},{"key":"ref95","doi-asserted-by":"publisher","first-page":"640","DOI":"10.1038\/374640a0","article-title":"Targeted disruption of the tyrosine hydroxylase gene reveals that catecholamines are required for mouse fetal development","volume":"374","author":"Zhou","year":"1995","journal-title":"Nature"},{"key":"ref96","doi-asserted-by":"publisher","first-page":"3800","DOI":"10.1182\/blood.v98.13.3800","article-title":"High concentrations of lipopolysaccharide-binding protein in serum of patients with severe sepsis or septic shock inhibit the lipopolysaccharide response in human monocytes","volume":"98","author":"Zweigner","year":"2001","journal-title":"Blood"}],"container-title":["Frontiers in Aging Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnagi.2022.986127\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,18]],"date-time":"2023-01-18T07:45:38Z","timestamp":1674027938000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnagi.2022.986127\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,18]]},"references-count":97,"alternative-id":["10.3389\/fnagi.2022.986127"],"URL":"https:\/\/doi.org\/10.3389\/fnagi.2022.986127","relation":{},"ISSN":["1663-4365"],"issn-type":[{"value":"1663-4365","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,18]]},"article-number":"986127"}}