{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T16:23:35Z","timestamp":1782145415711,"version":"3.54.5"},"reference-count":80,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T00:00:00Z","timestamp":1778198400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006013","name":"United Arab Emirates University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006013","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Parkinson\u2019s disease (PD), which is one of the most common neurodegenerative illnesses, involves abnormal deposition of \u03b1-Synuclein and loss of dopaminergic neurons in the substantia nigra. Beyond this, there is increasing evidence that the gut-brain axis (GBA) and blood-brain barrier (BBB) interfere in disease initiation and progression. Dysbiosis of the gut microbiota affects the intestine and the BBB, allowing microbial metabolites and proinflammatory mediators to enter the CNS, causing neuroinflammation and neurodegeneration. Studies show that \u03b1-Synuclein pathology can originate in the gut and reach the brain via the vagus nerve. This review summarizes the connections among GBA, BBB, and PD, focusing on oxidative damage, inflammatory cascades, decreased expression of tight junction proteins, and signaling pathways such as TLR4\/MyD88\/NF-\u03baB. In addition, we discuss therapeutic strategies that target the microbiota-BBB axis, such as probiotics, fecal microbiota transplantation, natural compounds (e.g., piperine, anethole, polymannuronic acid, Paeonia lactiflora), and stem cell therapy, which have demonstrated neuroprotective potential in animal models. Overall, the literature emphasizes the importance of restoring gut homeostasis and BBB integrity, and suggests that getting this axis right may offer novel opportunities for PD treatment. Future research is crucial to validate the efficacy of this approach clinically and to develop tailored therapies to prevent or delay PD progression.<\/jats:p>","DOI":"10.3389\/fphar.2026.1813134","type":"journal-article","created":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T05:57:01Z","timestamp":1778219821000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Neurodegeneration at the crossroads: the gut-brain axis and blood-brain barrier in Parkinson\u2019s disease \u2014 a review"],"prefix":"10.3389","volume":"17","author":[{"given":"Nada K.","family":"Gamal","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University","place":["Cairo, Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafik","family":"Fakhry","sequence":"additional","affiliation":[{"name":"PharmD Clinical Program, Faculty of Pharmacy, Ain Shams University","place":["Cairo, Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youmna","family":"Hatem","sequence":"additional","affiliation":[{"name":"PharmD Clinical Program, Faculty of Pharmacy, Ain Shams University","place":["Cairo, Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Engy","family":"Rashed","sequence":"additional","affiliation":[{"name":"PharmD Clinical Program, Faculty of Pharmacy, Ain Shams University","place":["Cairo, Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reem","family":"Marzouk","sequence":"additional","affiliation":[{"name":"PharmD Clinical Program, Faculty of Pharmacy, Ain Shams University","place":["Cairo, Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed K. M.","family":"Bukr","sequence":"additional","affiliation":[{"name":"PharmD Clinical Program, Faculty of Pharmacy, Ain Shams University","place":["Cairo, Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadia","family":"Akawi","sequence":"additional","affiliation":[{"name":"Department of Genetics and Genomics, College of Medicine and Health Sciences, United Arab Emirates University","place":["Al Ain, United Arab Emirates"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mina Y.","family":"George","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University","place":["Cairo, Egypt"]},{"name":"Biology Department, School of Pharmacy, Newgiza University","place":["Giza, Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"177217","DOI":"10.1016\/j.ejphar.2024.177217","article-title":"Silymarin nanoparticles counteract cognitive impairment induced by doxorubicin and cyclophosphamide in rats; insights into mitochondrial dysfunction and Nrf-2\/HO-1 axis","volume":"988","author":"Aboelnasr","year":"2025","journal-title":"Eur. J. Pharmacol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"6147","DOI":"10.3390\/ijms24076147","article-title":"Impact of pesticide residues on the gut-Microbiota\u2013Blood\u2013Brain barrier axis: a narrative review","volume":"24","author":"Abou Diwan","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"B3","doi-asserted-by":"publisher","first-page":"350","DOI":"10.1016\/j.aninu.2021.11.005","article-title":"Gut microbiota-derived short chain fatty acids are potential mediators in gut inflammation","volume":"8","author":"Akhtar","year":"2022","journal-title":"Anim. Nutr."},{"key":"B4","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1186\/s12974-015-0434-1","article-title":"Lipopolysaccharide-induced blood-brain barrier disruption: roles of cyclooxygenase, oxidative stress, neuroinflammation, and elements of the neurovascular unit","volume":"12","author":"Banks","year":"2015","journal-title":"J. Neuroinflammation"},{"key":"B5","doi-asserted-by":"publisher","first-page":"2440","DOI":"10.3390\/ijms26062440","article-title":"Impact of peripheral inflammation on blood\u2013brain barrier dysfunction and its role in neurodegenerative diseases","volume":"26","author":"Beltran-Velasco","year":"2025","journal-title":"Int. J. Mol. Sci."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1193","DOI":"10.1016\/j.neuroscience.2005.10.011","article-title":"Highly purified lipoteichoic acid from gram-positive bacteria induces in vitro blood\u2013brain barrier disruption through glia activation: role of pro-inflammatory cytokines and nitric oxide","volume":"137","author":"Boveri","year":"2006","journal-title":"Neuroscience"},{"key":"B7","doi-asserted-by":"publisher","first-page":"263ra158","DOI":"10.1126\/scitranslmed.3009759","article-title":"The gut microbiota influences blood-brain barrier permeability in mice","volume":"6","author":"Braniste","year":"2014","journal-title":"Sci. Transl. Med."},{"key":"B8","doi-asserted-by":"publisher","first-page":"849","DOI":"10.3389\/fneur.2020.00849","article-title":"Gut\u2013brain axis: potential factors involved in the pathogenesis of Parkinson's Disease","volume":"11","author":"Chao","year":"2020","journal-title":"Front. Neurology"},{"key":"B9","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1016\/S1474-4422(06)70373-8","article-title":"Non-motor symptoms of Parkinson's disease: diagnosis and management","volume":"5","author":"Chaudhuri","year":"2006","journal-title":"Lancet Neurology"},{"key":"B10","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s12276-018-0126-x","article-title":"Mechanisms regulating intestinal barrier integrity and its pathological implications","volume":"50","author":"Chelakkot","year":"2018","journal-title":"Exp. Mol. Med."},{"key":"B11","doi-asserted-by":"publisher","first-page":"11795735251370014","DOI":"10.1177\/11795735251370014","article-title":"Management of gastrointestinal symptoms in parkinson's Disease","volume":"17","author":"Chiang","year":"2025","journal-title":"J. Cent. Nerv. Syst. Dis."},{"key":"B12","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1186\/s40478-015-0196-0","article-title":"Structural alterations of the intestinal epithelial barrier in Parkinson's disease","volume":"3","author":"Clairembault","year":"2015","journal-title":"Acta Neuropathol. Commun."},{"key":"B13","doi-asserted-by":"publisher","first-page":"7735","DOI":"10.1038\/ncomms8735","article-title":"Microbiota and host determinants of behavioural phenotype in maternally separated mice","volume":"6","author":"De Palma","year":"2015","journal-title":"Nat. Commun."},{"key":"B14","doi-asserted-by":"publisher","first-page":"110491","DOI":"10.1016\/j.cbi.2023.110491","article-title":"Roflumilast escalates alpha-synuclein aggregate degradation in rotenone-induced Parkinson's disease in rats: modulation of the ubiquitin-proteasome system and endoplasmic reticulum stress","volume":"379","author":"Desouky","year":"2023","journal-title":"Chem. Biol. Interact."},{"key":"B15","doi-asserted-by":"publisher","first-page":"123206","DOI":"10.1016\/j.lfs.2024.123206","article-title":"Recent pharmacological insights on abating toxic protein species burden in neurological disorders: emphasis on 26S proteasome activation","volume":"359","author":"Desouky","year":"2024","journal-title":"Life Sci."},{"key":"B16","doi-asserted-by":"publisher","first-page":"246","DOI":"10.3389\/fnagi.2018.00246","article-title":"Natural molecules from Chinese herbs protecting against parkinson\u2019s disease via anti-oxidative stress","volume":"10","author":"Ding","year":"2018","journal-title":"Front. Aging Neurosci."},{"key":"B17","doi-asserted-by":"publisher","first-page":"742449","DOI":"10.3389\/fimmu.2021.742449","article-title":"Microbiota\u2013gut\u2013Brain axis and epilepsy: a review on mechanisms and potential therapeutics","volume":"12","author":"Ding","year":"2021","journal-title":"Front. Immunol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"994","DOI":"10.1016\/j.ijbiomac.2020.07.180","article-title":"Polymannuronic acid prevents dopaminergic neuronal loss via brain-gut-microbiota axis in Parkinson's disease model","volume":"164","author":"Dong","year":"2020","journal-title":"Int. J. Biol. Macromol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1007\/s00223-017-0331-y","article-title":"Gut Microbiota, immune System, and bone","volume":"102","author":"D\u2019amelio","year":"2018","journal-title":"Calcif. Tissue Int."},{"key":"B20","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":"B21","doi-asserted-by":"publisher","first-page":"114216","DOI":"10.1016\/j.intimp.2025.114216","article-title":"Neuromodulatory effect of troxerutin against doxorubicin and cyclophosphamide-induced cognitive impairment in rats: potential crosstalk between gut-brain and NLRP3 inflammasome axes","volume":"149","author":"Gamal","year":"2025","journal-title":"Int. Immunopharmacol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1080\/17425247.2023.2153831","article-title":"Design and evaluation of chrysin-loaded nanoemulsion against lithium\/pilocarpine-induced status epilepticus in rats; emphasis on formulation, neuronal excitotoxicity, oxidative stress, microglia polarization, and AMPK\/SIRT-1\/PGC-1alpha pathway","volume":"20","author":"George","year":"2023","journal-title":"Expert Opin. Drug Deliv."},{"key":"B23","doi-asserted-by":"publisher","first-page":"22","DOI":"10.3390\/medsci14010022","article-title":"From glucose transport to microbial modulation: the impact of sodium glucose Co-Transporter-2 inhibitors on the Gut Microbiota","volume":"14","author":"George","year":"2026","journal-title":"Med. Sci. (Basel)"},{"key":"B24","doi-asserted-by":"publisher","first-page":"1296","DOI":"10.1126\/science.aad2571","article-title":"The maternal microbiota drives early postnatal innate immune development","volume":"351","author":"Gomez De Ag\u00fcero","year":"2016","journal-title":"Science"},{"key":"B25","doi-asserted-by":"publisher","first-page":"e14846","DOI":"10.1111\/nmo.14846","article-title":"Associations between gut microbiota characteristics and non-motor symptoms following pharmacological and surgical treatments in Parkinson's disease patients","volume":"36","author":"Gorecka-Mazur","year":"2024","journal-title":"Neurogastroenterol. Motil."},{"key":"B26","doi-asserted-by":"publisher","first-page":"132982","DOI":"10.1016\/j.chemosphere.2021.132982","article-title":"Rotenone impairs learning and memory in mice through microglia-mediated blood brain barrier disruption and neuronal apoptosis","volume":"291","author":"Guo","year":"2022","journal-title":"Chemosphere"},{"key":"B27","doi-asserted-by":"publisher","first-page":"1574512","DOI":"10.3389\/fnins.2025.1574512","article-title":"Exploring the role of gut microbiota in Parkinson\u2019s disease: insights from fecal microbiota transplantation","volume":"19","author":"Guo","year":"2025","journal-title":"Front. Neurosci."},{"key":"B28","doi-asserted-by":"publisher","first-page":"1859","DOI":"10.1080\/17425247.2023.2228685","article-title":"Nose to brain delivery of naringin-loaded chitosan nanoparticles for potential use in oxaliplatin-induced chemobrain in rats: impact on oxidative stress, cGAS\/STING and HMGB1\/RAGE\/TLR2\/MYD88 inflammatory axes","volume":"20","author":"Hanna","year":"2023","journal-title":"Expert Opin. Drug Deliv."},{"key":"B29","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2014\/850493","article-title":"An in vivo microdialysis Study of FLZ penetration through the blood-brain barrier in normal and 6-Hydroxydopamine induced parkinson\u2019s disease model rats","volume":"2014","author":"Hou","year":"2014","journal-title":"BioMed Res. Int."},{"key":"B30","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1038\/s41531-016-0002-0","article-title":"The gut-brain axis: is intestinal inflammation a silent driver of Parkinson's disease pathogenesis?","volume":"3","author":"Houser","year":"2017","journal-title":"NPJ Park. Dis."},{"key":"B31","doi-asserted-by":"publisher","first-page":"1023","DOI":"10.1096\/fj.09-141978","article-title":"Cellular mechanisms of IL\u201017\u2010induced blood\u2010brain barrier disruption","volume":"24","author":"Huppert","year":"2010","journal-title":"FASEB J."},{"key":"B32","doi-asserted-by":"publisher","first-page":"108738","DOI":"10.1016\/j.neuropharm.2021.108738","article-title":"Nose-to-brain delivery of chrysin transfersomal and composite vesicles in doxorubicin-induced cognitive impairment in rats: insights on formulation, oxidative stress and TLR4\/NF-kB\/NLRP3 pathways","volume":"197","author":"Ibrahim","year":"2021","journal-title":"Neuropharmacology"},{"key":"B33","doi-asserted-by":"publisher","first-page":"896","DOI":"10.1016\/S0140-6736(14)61393-3","article-title":"Parkinson's disease","volume":"386","author":"Kalia","year":"2015","journal-title":"Lancet"},{"key":"B34","doi-asserted-by":"publisher","first-page":"1173","DOI":"10.1038\/nm1651","article-title":"Human TH17 lymphocytes promote blood-brain barrier disruption and central nervous system inflammation","volume":"13","author":"Kebir","year":"2007","journal-title":"Nat. Med."},{"key":"B35","doi-asserted-by":"publisher","first-page":"392","DOI":"10.3389\/fncel.2015.00392","article-title":"Breaking down the barriers: the gut microbiome, intestinal permeability and stress-related psychiatric disorders","volume":"9","author":"Kelly","year":"2015","journal-title":"Front. Cell Neurosci."},{"key":"B36","doi-asserted-by":"publisher","first-page":"1351","DOI":"10.1002\/mds.26307","article-title":"Colonic bacterial composition in Parkinson's disease","volume":"30","author":"Keshavarzian","year":"2015","journal-title":"Mov. Disord."},{"key":"B37","doi-asserted-by":"publisher","first-page":"528","DOI":"10.1038\/nature23910","article-title":"Maternal gut bacteria promote neurodevelopmental abnormalities in mouse offspring","volume":"549","author":"Kim","year":"2017","journal-title":"Nature"},{"key":"B38","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1186\/s40035-024-00430-z","article-title":"Blood-brain barrier alterations and their impact on Parkinson's disease pathogenesis and therapy","volume":"13","author":"Lau","year":"2024","journal-title":"Transl. Neurodegener."},{"key":"B39","doi-asserted-by":"publisher","first-page":"272","DOI":"10.2741\/4206","article-title":"Disruption of the blood-brain barrier in Parkinson'S disease: curse or route to a cure?","volume":"19","author":"Lee","year":"2014","journal-title":"Front. Biosci."},{"key":"B40","doi-asserted-by":"publisher","first-page":"10600","DOI":"10.3390\/ijms241310600","article-title":"Probing gut participation in parkinson\u2019s disease pathology and treatment via stem cell therapy","volume":"24","author":"Lee","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"B41","doi-asserted-by":"publisher","first-page":"e371104","DOI":"10.1590\/acb371104","article-title":"Er-Bai-Tang decoction improved the movement disorders and neuronal injury in the Parkinson\u2019s disease model rats via decreasing p38 MAPK pathway and improving the composition of intestinal flora","volume":"37","author":"Li","year":"2022","journal-title":"Acta Cir\u00fargica Bras."},{"key":"B42","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1021\/acs.jafc.1c06998","article-title":"Effect of coffee against MPTP-Induced motor deficits and neurodegeneration in mice via regulating Gut microbiota","volume":"70","author":"Liu","year":"2022","journal-title":"J. Agric. Food Chem."},{"key":"B43","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1177\/1535370217743766","article-title":"Gut reactions: how the blood\u2013brain barrier connects the microbiome and the brain","volume":"243","author":"Logsdon","year":"2018","journal-title":"Exp. Biol. Med."},{"key":"B44","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":"2020","journal-title":"J. Neurology"},{"key":"B45","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1007\/s40263-024-01073-4","article-title":"The gut microbiota in parkinson disease: interactions with drugs and potential for therapeutic applications","volume":"38","author":"Menozzi","year":"2024","journal-title":"CNS Drugs"},{"key":"B46","doi-asserted-by":"publisher","first-page":"777","DOI":"10.1007\/s10787-023-01384-w","article-title":"Empagliflozin repurposing in parkinson's disease; modulation of oxidative stress, neuroinflammation, AMPK\/SIRT-1\/PGC-1alpha, and wnt\/beta-catenin pathways","volume":"32","author":"Mohammed","year":"2024","journal-title":"Inflammopharmacology"},{"key":"B47","doi-asserted-by":"publisher","first-page":"e0294612","DOI":"10.1371\/journal.pone.0294612","article-title":"Anethole attenuates motor dysfunctions, striatal neuronal activity deficiency and blood brain barrier permeability by decreasing striatal \u03b1-synuclein and oxidative stress in rotenone-induced Parkinson\u2019s disease of Male rats","volume":"18","author":"Moradi Vastegani","year":"2023","journal-title":"PLOS ONE"},{"key":"B48","doi-asserted-by":"publisher","first-page":"310","DOI":"10.1007\/s11481-023-10062-1","article-title":"L-carnitine modulates cognitive impairment induced by Doxorubicin and cyclophosphamide in rats; insights to oxidative stress, inflammation, synaptic plasticity, Liver\/brain, and Kidney\/brain axes","volume":"18","author":"Morid","year":"2023","journal-title":"J. Neuroimmune Pharmacol."},{"key":"B49","doi-asserted-by":"publisher","first-page":"796288","DOI":"10.3389\/fimmu.2022.796288","article-title":"Gut Microbiota interact with the brain through systemic chronic inflammation: implications on neuroinflammation, neurodegeneration, and aging","volume":"13","author":"Mou","year":"2022","journal-title":"Front. Immunol."},{"key":"B50","doi-asserted-by":"publisher","first-page":"727","DOI":"10.1016\/j.neubiorev.2016.07.010","article-title":"Motor symptoms in Parkinson\u2019s disease: a unified framework","volume":"68","author":"Moustafa","year":"2016","journal-title":"Neurosci. and Biobehav. Rev."},{"key":"B51","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1038\/s41591-018-0297-y","article-title":"Blood\u2013brain barrier breakdown is an early biomarker of human cognitive dysfunction","volume":"25","author":"Nation","year":"2019","journal-title":"Nat. Med."},{"key":"B52","doi-asserted-by":"publisher","first-page":"e21201","DOI":"10.1096\/fj.202001117R","article-title":"The gut microbiome contributes to blood\u2010brain barrier disruption in spontaneously hypertensive stroke prone rats","volume":"35","author":"Nelson","year":"2021","journal-title":"FASEB J."},{"key":"B53","doi-asserted-by":"publisher","first-page":"521","DOI":"10.1111\/nmo.12110","article-title":"Commensal microbiota modulate murine behaviors in a strictly contamination\u2010free environment confirmed by culture\u2010based methods","volume":"25","author":"Nishino","year":"2013","journal-title":"Neurogastroenterol. and Motil."},{"key":"B54","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1016\/j.neuroscience.2015.09.068","article-title":"Early-life adversity and brain development: is the microbiome a missing piece of the puzzle?","volume":"342","author":"O\u2019mahony","year":"2017","journal-title":"Neuroscience"},{"key":"B55","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1080\/19490976.2019.1638722","article-title":"Gut microbes and metabolites as modulators of blood-brain barrier integrity and brain health","volume":"11","author":"Parker","year":"2020","journal-title":"Gut Microbes"},{"key":"B56","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. Prim."},{"key":"B57","doi-asserted-by":"publisher","first-page":"274","DOI":"10.1016\/j.bbrc.2018.11.021","article-title":"IFN-\u03b3, IL-17A, or zonulin rapidly increase the permeability of the blood-brain and small intestinal epithelial barriers: relevance for neuro-inflammatory diseases","volume":"507","author":"Rahman","year":"2018","journal-title":"Biochem. Biophysical Res. Commun."},{"key":"B58","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 Park. Dis."},{"key":"B59","doi-asserted-by":"publisher","first-page":"1999","DOI":"10.1212\/wnl.0000000000012826","article-title":"Trends in mortality from parkinson disease in the United States","volume":"97","author":"Rong","year":"2021","journal-title":"Neurology"},{"key":"B60","doi-asserted-by":"publisher","first-page":"100212","DOI":"10.1016\/j.crtox.2024.100212","article-title":"The role of the gut microbiota and the nicotinate\/nicotinamide pathway in rotenone-induced neurotoxicity","volume":"8","author":"Sai","year":"2025","journal-title":"Curr. Res. Toxicol."},{"key":"B61","doi-asserted-by":"publisher","first-page":"276","DOI":"10.1007\/s11481-008-9138-y","article-title":"Lipopolysaccharide impairs blood\u2013brain barrier P-glycoprotein function in mice through Prostaglandin- and nitric oxide-independent pathways","volume":"4","author":"Salkeni","year":"2009","journal-title":"J. Neuroimmune Pharmacol."},{"key":"B62","doi-asserted-by":"publisher","first-page":"350","DOI":"10.1002\/mds.26069","article-title":"Gut microbiota are related to Parkinson's disease and clinical phenotype","volume":"30","author":"Scheperjans","year":"2015","journal-title":"Mov. Disord."},{"key":"B63","doi-asserted-by":"publisher","first-page":"383","DOI":"10.4161\/gmic.21008","article-title":"Stabilization of the murine gut microbiome following weaning","volume":"3","author":"Schloss","year":"2012","journal-title":"Gut Microbes"},{"key":"B64","doi-asserted-by":"publisher","first-page":"833","DOI":"10.1142\/S0192415X25500314","article-title":"Neuroprotective effects of Paeonia lactiflora through the regulation of gut dubosiella in an MPTP-Induced parkinson\u2019s disease mouse model","volume":"53","author":"Shao","year":"2025","journal-title":"Am. J. Chin. Med."},{"key":"B65","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1007\/s12031-025-02462-0","article-title":"Unfolding Parkinson's Disease through the microbiome-gut-brain axis","volume":"76","author":"Shenthilvel","year":"2026","journal-title":"J. Mol. Neurosci."},{"key":"B66","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1128\/microbiolspec.MBP-0008-2014","article-title":"The roles of inflammation, nutrient availability and the commensal Microbiota in enteric pathogen infection","volume":"3","author":"Stecher","year":"2015","journal-title":"Microbiol. Spectr."},{"key":"B67","first-page":"9","article-title":"Brain development and the role of experience in the early years","volume":"30","author":"Tierney","year":"2009","journal-title":"Zero Three"},{"key":"B68","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1007\/s00018-022-04240-2","article-title":"Initiation and progression of \u03b1-synuclein pathology in Parkinson\u2019s disease","volume":"79","author":"Tofaris","year":"2022","journal-title":"Cell. Mol. Life Sci."},{"key":"B69","doi-asserted-by":"publisher","first-page":"1823","DOI":"10.3390\/antiox10111823","article-title":"Probiotic enhancement of antioxidant capacity and alterations of Gut Microbiota composition in 6-Hydroxydopamin-Induced parkinson\u2019s disease rats","volume":"10","author":"Tsao","year":"2021","journal-title":"Antioxidants"},{"key":"B70","doi-asserted-by":"publisher","first-page":"105691","DOI":"10.1016\/j.neuint.2024.105691","article-title":"Supplementation of probiotic Bifidobacterium breve Bif11 reverses neurobehavioural deficits, inflammatory changes and oxidative stress in Parkinson's disease model","volume":"174","author":"Valvaikar","year":"2024","journal-title":"Neurochem. Int."},{"key":"B71","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":"B72","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s12031-013-0175-5","article-title":"Effects of poly (ADP-ribose) polymerase inhibitor 3-Aminobenzamide on blood\u2013brain barrier and dopaminergic neurons of rats with lipopolysaccharide-induced parkinson\u2019s disease","volume":"53","author":"Wu","year":"2014","journal-title":"J. Mol. Neurosci."},{"key":"B73","doi-asserted-by":"publisher","first-page":"2193","DOI":"10.14336\/AD.2023.0309","article-title":"Healthy human fecal microbiota transplantation into mice attenuates MPTP-Induced neurotoxicity via AMPK\/SOD2 pathway","volume":"14","author":"Xie","year":"2023","journal-title":"Aging Disease"},{"key":"B74","doi-asserted-by":"publisher","first-page":"156296","DOI":"10.1016\/j.phymed.2024.156296","article-title":"Study on the anti-parkinson's disease activity mechanism and preparation of panaxadiol","volume":"136","author":"Xu","year":"2025","journal-title":"Phytomedicine"},{"key":"B75","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.neuroscience.2025.07.003","article-title":"Parkinson\u2019s disease and the gut microbiota connection: unveiling dysbiosis and exploring therapeutic horizons","volume":"581","author":"Yadav","year":"2025","journal-title":"Neuroscience"},{"key":"B76","doi-asserted-by":"publisher","first-page":"1041","DOI":"10.3390\/pharmaceutics17081041","article-title":"Overcoming the blood\u2013brain barrier: advanced strategies in targeted drug delivery for neurodegenerative diseases","volume":"17","author":"Yang","year":"2025","journal-title":"Pharmaceutics"},{"key":"B77","doi-asserted-by":"publisher","first-page":"117628","DOI":"10.1016\/j.jep.2023.117628","article-title":"Piperine promotes PI3K\/AKT\/mTOR-mediated gut-brain autophagy to degrade \u03b1-Synuclein in Parkinson\u2019s disease rats","volume":"322","author":"Yu","year":"2024","journal-title":"J. Ethnopharmacol."},{"key":"B78","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1186\/s40035-023-00392-8","article-title":"Parkinson's disease and gut microbiota: from clinical to mechanistic and therapeutic studies","volume":"12","author":"Zhang","year":"2023","journal-title":"Transl. Neurodegener."},{"key":"B79","doi-asserted-by":"publisher","first-page":"155530","DOI":"10.1016\/j.phymed.2024.155530","article-title":"Notoginsenoside R1 alleviates cerebral ischemia\/reperfusion injury by inhibiting the TLR4\/MyD88\/NF-\u03baB signaling pathway through microbiota-gut-brain axis","volume":"128","author":"Zhang","year":"2024","journal-title":"Phytomedicine"},{"key":"B80","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1186\/s40168-021-01107-9","article-title":"Fecal microbiota transplantation protects rotenone-induced Parkinson\u2019s disease mice via suppressing inflammation mediated by the lipopolysaccharide-TLR4 signaling pathway through the microbiota-gut-brain axis","volume":"9","author":"Zhao","year":"2021","journal-title":"Microbiome"}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1813134\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T05:57:03Z","timestamp":1778219823000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1813134\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,8]]},"references-count":80,"alternative-id":["10.3389\/fphar.2026.1813134"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2026.1813134","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,8]]},"article-number":"1813134"}}