{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T17:29:30Z","timestamp":1785432570479,"version":"3.56.0"},"reference-count":71,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T00:00:00Z","timestamp":1784764800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program","doi-asserted-by":"publisher","award":["2026CXPT280"],"award-info":[{"award-number":["2026CXPT280"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Shandong Province Key R&amp;D Program","award":["2025TSGCCZZB0800"],"award-info":[{"award-number":["2025TSGCCZZB0800"]}]},{"name":"Shandong Institute of Advanced Technology","award":["202534063"],"award-info":[{"award-number":["202534063"]}]},{"award":["202534063"],"award-info":[{"award-number":["202534063"]}],"id":[{"id":"https:\/\/ror.org\/02n7p8p77","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Shenzhen University Health Science Center","award":["JCYJ20190809160209449"],"award-info":[{"award-number":["JCYJ20190809160209449"]}]},{"award":["JCYJ20190809160209449"],"award-info":[{"award-number":["JCYJ20190809160209449"]}],"id":[{"id":"https:\/\/ror.org\/04yjbr930","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["22278343"],"award-info":[{"award-number":["22278343"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["22278343"],"award-info":[{"award-number":["22278343"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Parkinson\u2019s disease (PD), a debilitating neurodegenerative disorder, is primarily characterized by motor impairments and concurrent gastrointestinal disturbances. Increasing evidence has highlighted the critical role of the microbiota\u2013gut\u2013brain axis (MGBA) in the pathogenesis of PD. This study investigated the neuroprotective potential of sodium hyaluronate (SH) in a mouse model of PD and its underlying mechanisms via the MGBA. In the oral pre-treatment study, three doses (7.5, 15, and 30 mg\/kg\/day) were evaluated. The results showed that the high dose (SH-H, 30 mg\/kg\/day) significantly ameliorated motor disorders and gastrointestinal functional disorders. Therefore, SH-H was selected for subsequent mechanistic investigations. Mechanistically, SH-H restored gut microbiota homeostasis, increased fecal short-chain fatty acid (SCFA) levels, and improved the integrity of the intestinal and blood\u2013brain barrier (BBB). Thus, SH reduced the transfer of lipopolysaccharide (LPS) from the intestine to serum and the substantia nigra (SN), suppressing activation of the LPS-TLR4\/MyD88\/NF-\u03baB signaling pathway. These effects alleviated neuroinflammation, protected dopaminergic neurons, and reduced the aggregation of \u03b1-synuclein (\u03b1-syn). In summary, SH attenuated PD-related pathological changes by restoring gut microbiota homeostasis and modulating the MGBA, suggesting that SH may represent a potential therapeutic strategy for PD.<\/jats:p>","DOI":"10.3390\/ijms27156573","type":"journal-article","created":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T17:13:17Z","timestamp":1784826797000},"page":"6573","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Oral Sodium Hyaluronate Reshapes Gut Microbiota Composition and Suppresses the LPS-TLR4\/NF-\u03baB Pathway to Exert Neuroprotection in MPTP-Induced Parkinson\u2019s Disease"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-2202-2296","authenticated-orcid":false,"given":"Yishu","family":"Wang","sequence":"first","affiliation":[{"name":"Key Laboratory of Brain, Cognition and Education Sciences, Ministry of Education, Institute for Brain Research and Rehabilitation, South China Normal University, Guangzhou 510631, China"},{"name":"Shandong Academy of Pharmaceutical Sciences, Engineering Research Center for Sugar and Sugar Complex, National-Local Joint Engineering Laboratory of Polysaccharide Drugs, Key Laboratory of Carbohydrate and Glycoconjugate Drugs, Jinan 250101, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8203-9715","authenticated-orcid":false,"given":"Zhi","family":"Cao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Brain, Cognition and Education Sciences, Ministry of Education, Institute for Brain Research and Rehabilitation, South China Normal University, Guangzhou 510631, China"},{"name":"The Second Clinical Medical College, Jinan University, Shenzhen 518020, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Shandong Academy of Pharmaceutical Sciences, Engineering Research Center for Sugar and Sugar Complex, National-Local Joint Engineering Laboratory of Polysaccharide Drugs, Key Laboratory of Carbohydrate and Glycoconjugate Drugs, Jinan 250101, China"},{"name":"College of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250355, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Ying","sequence":"additional","affiliation":[{"name":"Shandong Academy of Pharmaceutical Sciences, Engineering Research Center for Sugar and Sugar Complex, National-Local Joint Engineering Laboratory of Polysaccharide Drugs, Key Laboratory of Carbohydrate and Glycoconjugate Drugs, Jinan 250101, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaofei","family":"Zhu","sequence":"additional","affiliation":[{"name":"Shandong Academy of Pharmaceutical Sciences, Engineering Research Center for Sugar and Sugar Complex, National-Local Joint Engineering Laboratory of Polysaccharide Drugs, Key Laboratory of Carbohydrate and Glycoconjugate Drugs, Jinan 250101, China"},{"name":"College of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250355, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Wang","sequence":"additional","affiliation":[{"name":"Shandong Academy of Pharmaceutical Sciences, Engineering Research Center for Sugar and Sugar Complex, National-Local Joint Engineering Laboratory of Polysaccharide Drugs, Key Laboratory of Carbohydrate and Glycoconjugate Drugs, Jinan 250101, China"},{"name":"College of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250355, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyu","family":"Hou","sequence":"additional","affiliation":[{"name":"Shandong Academy of Pharmaceutical Sciences, Engineering Research Center for Sugar and Sugar Complex, National-Local Joint Engineering Laboratory of Polysaccharide Drugs, Key Laboratory of Carbohydrate and Glycoconjugate Drugs, Jinan 250101, China"},{"name":"College of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250355, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daizhou","family":"Zhang","sequence":"additional","affiliation":[{"name":"Shandong Academy of Pharmaceutical Sciences, Engineering Research Center for Sugar and Sugar Complex, National-Local Joint Engineering Laboratory of Polysaccharide Drugs, Key Laboratory of Carbohydrate and Glycoconjugate Drugs, Jinan 250101, China"},{"name":"College of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250355, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyong","family":"Zheng","sequence":"additional","affiliation":[{"name":"Shandong Academy of Pharmaceutical Sciences, Engineering Research Center for Sugar and Sugar Complex, National-Local Joint Engineering Laboratory of Polysaccharide Drugs, Key Laboratory of Carbohydrate and Glycoconjugate Drugs, Jinan 250101, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huarong","family":"Shao","sequence":"additional","affiliation":[{"name":"Shandong Academy of Pharmaceutical Sciences, Engineering Research Center for Sugar and Sugar Complex, National-Local Joint Engineering Laboratory of Polysaccharide Drugs, Key Laboratory of Carbohydrate and Glycoconjugate Drugs, Jinan 250101, China"},{"name":"College of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250355, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Liu","sequence":"additional","affiliation":[{"name":"Shandong Academy of Pharmaceutical Sciences, Engineering Research Center for Sugar and Sugar Complex, National-Local Joint Engineering Laboratory of Polysaccharide Drugs, Key Laboratory of Carbohydrate and Glycoconjugate Drugs, Jinan 250101, China"},{"name":"College of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250355, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaodong","family":"Ma","sequence":"additional","affiliation":[{"name":"Key Laboratory of Brain, Cognition and Education Sciences, Ministry of Education, Institute for Brain Research and Rehabilitation, South China Normal University, Guangzhou 510631, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,23]]},"reference":[{"key":"ref_1","first-page":"10283","article-title":"The epidemiology of Parkinson\u2019s disease","volume":"403","author":"Darweesh","year":"2024","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Benvenuti, L., Di Salvo, C., Bellini, G., Seguella, L., Rettura, F., Esposito, G., Antonioli, L., Ceravolo, R., Bernardini, N., and Pellegrini, C. (2024). Gut-directed therapy in Parkinson\u2019s disease. Front. Pharmacol., 15.","DOI":"10.3389\/fphar.2024.1407925"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"9873","DOI":"10.1007\/s12035-023-03691-3","article-title":"Gut-Brain Axis a Key Player to Control Gut Dysbiosis in Neurological Diseases","volume":"61","author":"Pan","year":"2024","journal-title":"Mol. Neurobiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1038\/s41531-024-00681-7","article-title":"Diet and the gut microbiome in patients with Parkinson\u2019s disease","volume":"10","author":"Kwon","year":"2024","journal-title":"NPJ Park. Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1038\/s41422-019-0216-x","article-title":"Sodium oligomannate therapeutically remodels gut microbiota and suppresses gut bacterial amino acids-shaped neuroinflammation to inhibit Alzheimer\u2019s disease progression","volume":"29","author":"Wang","year":"2019","journal-title":"Cell Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/bs.pbr.2020.01.004","article-title":"The gut microbiome in Parkinson\u2019s disease: A culprit or a bystander?","volume":"252","author":"Keshavarzian","year":"2020","journal-title":"Prog. Brain Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"100533","DOI":"10.1016\/j.crfs.2023.100533","article-title":"Lactoferrin alleviates Western diet-induced cognitive impairment through the microbiome-gut-brain axis","volume":"7","author":"He","year":"2023","journal-title":"Curr. Res. Food Sci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1111\/jnc.15915","article-title":"Hyaluronan hydrates and compartmentalises the CNS\/PNS extracellular matrix and provides niche environments conducive to the optimisation of neuronal activity","volume":"166","author":"Melrose","year":"2023","journal-title":"J. Neurochem"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"7196","DOI":"10.1038\/s41586-023-06463-0","article-title":"Increased hyaluronan by naked mole-rat Has2 improves healthspan in mice","volume":"621","author":"Zhang","year":"2023","journal-title":"Nature"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"4829","DOI":"10.1038\/s41467-021-25025-4","article-title":"Adipose tissue hyaluronan production improves systemic glucose homeostasis and primes adipocytes for CL 316,243-stimulated lipolysis","volume":"12","author":"Zhu","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/bs.pmbts.2020.08.012","article-title":"The microbiota-gut-brain axis: Focus on the fundamental communication pathways","volume":"176","author":"Bistoletti","year":"2020","journal-title":"Prog. Mol. Biol. Transl. Sci."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Bosi, A.A.-O.X., Banfi, D., Bistoletti, M., Moretto, P., Moro, E., Crema, F., Maggi, F.A.-O., Karousou, E., Viola, M.A.-O., and Passi, A.A.-O. (2021). Hyaluronan: A neuroimmune modulator in the microbiota-gut axis. Cells, 11.","DOI":"10.3390\/cells11010126"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.matbio.2016.11.001","article-title":"Hyaluronan 35kDa treatment protects mice from Citrobacter rodentium infection and induces epithelial tight junction protein ZO-1 in vivo","volume":"62","author":"Kim","year":"2017","journal-title":"Matrix Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1002\/hep.29144","article-title":"MicroRNA 181b-3p and its target importin \u03b15 regulate toll-like receptor 4 signaling in Kupffer cells and liver injury in mice in response to ethanol","volume":"66","author":"Saikia","year":"2017","journal-title":"Hepatology"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Marinho, A., Nunes, C., and Reis, S.A.-O. (2021). Hyaluronic Acid: A Key Ingredient in the Therapy of Inflammation. Biomolecules, 11.","DOI":"10.3390\/biom11101518"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"118320","DOI":"10.1016\/j.carbpol.2021.118320","article-title":"Current advances in the biosynthesis of hyaluronic acid with variable molecular weights","volume":"269","author":"Qiu","year":"2021","journal-title":"Carbohydr. Polym."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1136\/gut.28.10.1221","article-title":"Short chain fatty acids in human large intestine, portal, hepatic and venous blood","volume":"28","author":"Cummings","year":"1987","journal-title":"Gut"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1038\/s41577-024-01014-8","article-title":"Short-chain fatty acids: Linking diet, the microbiome and immunity","volume":"24","author":"Mann","year":"2024","journal-title":"Nat. Rev. Immunol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1841","DOI":"10.1007\/s12035-018-1188-4","article-title":"The gut microbiome alterations and inflammation-driven pathogenesis of Alzheimer\u2019s disease-a critical review","volume":"56","author":"Sochocka","year":"2018","journal-title":"Mol. Neurobiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1038\/s41575-019-0157-3","article-title":"The role of short-chain fatty acids in microbiota-gut-brain communication","volume":"16","author":"Dalile","year":"2019","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.parkreldis.2016.08.019","article-title":"Short chain fatty acids and gut microbiota differ between patients with Parkinson\u2019s disease and age-matched controls","volume":"32","author":"Unger","year":"2016","journal-title":"Park. Relat. Disord."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Obrenovich, M.E.M. (2018). Leaky gut, leaky brain?. Microorganisms, 6.","DOI":"10.3390\/microorganisms6040107"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"9896","DOI":"10.1016\/S0140-6736(14)61393-3","article-title":"Parkinson\u2019s disease","volume":"386","author":"Kalia","year":"2015","journal-title":"Lancet"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"100888","DOI":"10.1016\/j.crfs.2024.100888","article-title":"Targeting protein aggregation using a cocoa-bean shell extract to reduce \u03b1-synuclein toxicity in models of Parkinson\u2019s disease","volume":"9","author":"Tripodi","year":"2024","journal-title":"Curr. Res. Food Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1164","DOI":"10.1172\/JCI58644","article-title":"Innate immunity in the central nervous system","volume":"122","author":"Ransohoff","year":"2012","journal-title":"J. Clin. Invest"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"101618","DOI":"10.1016\/j.arr.2022.101618","article-title":"Reducing neuroinflammation via therapeutic compounds and lifestyle to prevent or delay progression of Parkinson\u2019s disease","volume":"78","author":"Kip","year":"2022","journal-title":"Ageing Res. Rev."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"104814","DOI":"10.1016\/j.nbd.2020.104814","article-title":"Neuroprotection by dihydrotestosterone in LPS-induced neuroinflammation","volume":"140","author":"Yang","year":"2020","journal-title":"Neurobiol. Dis."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1136\/gutjnl-2018-316844","article-title":"Role of TLR4 in the gut-brain axis in Parkinson\u2019s disease: A translational study from men to mice","volume":"68","author":"Dodiya","year":"2019","journal-title":"Gut"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"105803","DOI":"10.1016\/j.neuint.2024.105803","article-title":"Modulating the biosynthesis and TLR4-interaction of lipopolysaccharide as an approach to counter gut dysbiosis and Parkinson\u2019s disease: Role of phyto-compounds","volume":"178","author":"Roy","year":"2024","journal-title":"Neurochem. Int."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.arr.2017.02.004","article-title":"Targeting the TLR4 signaling pathway by polyphenols: A novel therapeutic strategy for neuroinflammation","volume":"36","author":"Rahimifard","year":"2017","journal-title":"Ageing Res. Rev."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Varesi, A.C.L., Fahmideh, F., Pierella, E., Romeo, M., Ricevuti, G., Nicoletta, M., Chirumbolo, S., and Pascale, A. (2022). The interplay between gut microbiota and Parkinson\u2019s disease: Implications on diagnosis and treatment. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232012289"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1675","DOI":"10.1111\/cns.13916","article-title":"New hope for Parkinson\u2019s disease treatment: Targeting gut microbiota","volume":"28","author":"Fan","year":"2022","journal-title":"CNS Neurosci. Ther."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1159\/000518147","article-title":"Parkinson\u2019s disease and gut microbiota","volume":"77","author":"Hirayama","year":"2021","journal-title":"Ann. Nutr. Metab."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1038\/s41582-022-00681-2","article-title":"The microbiome-gut-brain axis in Parkinson disease\u2014From basic research to the clinic","volume":"18","author":"Tan","year":"2022","journal-title":"Nat. Rev. Neurol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"6655","DOI":"10.1007\/s12035-024-04253-x","article-title":"Selenium Nanoparticles as Neuroprotective Agents: Insights into Molecular Mechanisms for Parkinson\u2019s Disease Treatment","volume":"62","author":"Umapathy","year":"2025","journal-title":"Mol. Neurobiol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2947","DOI":"10.1111\/bph.16382","article-title":"Daidzein ameliorates nonmotor symptoms of manganese-induced Parkinsonism in zebrafish model: Behavioural and biochemical approach","volume":"181","author":"Haridevamuthu","year":"2024","journal-title":"Br. J. Pharmacol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41420-025-02906-x","article-title":"Melatonin orchestrates mitochondrial fusion dynamics-mediated WNT\/\u03b2-catenin signaling to promote dopaminergic neuronal differentiation of human iPS and nerve regeneration in a MPTP-induced mouse model of Parkinson\u2019s disease","volume":"12","author":"Zhang","year":"2025","journal-title":"Cell Death Discov."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1038\/s41522-025-00855-y","article-title":"Alternate-day fasting ameliorates \u03b1-synuclein pathology and suppresses inflammation via the gut-brain axis in an MPTP-induced subacute mouse model of Parkinson\u2019s disease","volume":"11","author":"Wang","year":"2025","journal-title":"NPJ Biofilms Microbiomes"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1016\/j.freeradbiomed.2024.02.023","article-title":"Neuroprotective effects of cordycepin on MPTP-induced Parkinson\u2019s disease mice via suppressing PI3K\/AKT\/mTOR and MAPK-mediated neuroinflammation","volume":"216","author":"Wang","year":"2024","journal-title":"Free Radic. Biol. Med."},{"key":"ref_40","first-page":"422","article-title":"MPTP-induced mouse model of Parkinson\u2019s disease: A promising direction of therapeutic strategies","volume":"21","author":"Mustapha","year":"2021","journal-title":"Bosn. J. Basic Med. Sci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"117871","DOI":"10.1016\/j.biopha.2025.117871","article-title":"Activation of \u03b17nAch receptors ameliorates \u03b1-synuclein pathology in the brain and gut of a subacute MPTP mouse model of Parkinson\u2019s disease","volume":"184","author":"Leem","year":"2025","journal-title":"BioMed Pharmacother."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1919","DOI":"10.2147\/NDT.S481252","article-title":"Atractylenolide-I Ameliorates Motor Deficits and Reduces Inflammation of the Spinal Cord by SIRT1\/PGC-1\u03b1 Pathway in MPTP Subacute Mouse Model of Parkinson\u2019s Disease","volume":"20","author":"Gao","year":"2024","journal-title":"Neuropsychiatr. Dis. Treat."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/j.neuro.2019.11.009","article-title":"Twice subacute MPTP administrations induced time-dependent dopaminergic neurodegeneration and inflammation in midbrain and ileum, as well as gut microbiota disorders in PD mice","volume":"76","author":"Xie","year":"2020","journal-title":"Neurotoxicology"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1007\/s13311-019-00719-2","article-title":"Neuroprotection of fasting mimicking diet on MPTP-induced Parkinson\u2019s disease mice via gut microbiota and metabolites","volume":"16","author":"Zhou","year":"2019","journal-title":"Neurotherapeutics"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"4227","DOI":"10.1038\/s41467-025-56829-3","article-title":"Machine learning-based meta-analysis reveals gut microbiome alterations associated with Parkinson\u2019s disease","volume":"16","author":"Romano","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"e0033820","DOI":"10.1128\/CMR.00338-20","article-title":"A Comprehensive Review on the Role of the Gut Microbiome in Human Neurological Disorders","volume":"35","author":"Sorboni","year":"2022","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.parkreldis.2021.12.012","article-title":"Altered gut microbiota in Parkinson\u2019s disease patients with motor complications","volume":"95","author":"Takahashi","year":"2022","journal-title":"Park. Relat. Disord."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1038\/s41531-022-00327-6","article-title":"Probiotics synergized with conventional regimen in managing Parkinson\u2019s disease","volume":"8","author":"Sun","year":"2022","journal-title":"NPJ Park. Dis."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1016\/j.tibtech.2021.10.005","article-title":"Dynamic regulation of gut Clostridium-derived short-chain fatty acids","volume":"40","author":"Zhu","year":"2022","journal-title":"Trends Biotechnol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1016\/j.bbi.2020.10.014","article-title":"Probiotic Clostridium butyricum ameliorated motor deficits in a mouse model of Parkinson\u2019s disease via gut microbiota-GLP-1 pathway","volume":"91","author":"Sun","year":"2021","journal-title":"Brain Behav. Immun."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"118239","DOI":"10.1016\/j.foodres.2025.118239","article-title":"Lactobacillus rhamnosus RL-H3-005 ameliorates Enterococcus faecium-induced pulmonary inflammation via gut microbiota remodeling and macrophage polarization regulation","volume":"226","author":"Li","year":"2026","journal-title":"Food Res. Int."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1186\/s12964-025-02448-w","article-title":"Resveratrol alleviates IBD-associated neuropsychiatric comorbidities via microbiota-dependent arginine metabolism reprogramming and microglial M2 polarization through gut-brain axis","volume":"23","author":"Fan","year":"2025","journal-title":"Cell Commun. Signal"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"115008","DOI":"10.1016\/j.physbeh.2025.115008","article-title":"Gut microbial dysbiosis aggravated Parkinson-like pathology induced by MPTP\/probenecid","volume":"299","author":"Chen","year":"2025","journal-title":"Physiol. Behav."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1007\/s10482-025-02097-6","article-title":"The impact of climate, weather, seasonal transitions, and diurnal rhythms on gut microbiota and immune homeostasis","volume":"118","author":"Aswinanand","year":"2025","journal-title":"Antonie Van Leeuwenhoek"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1863","DOI":"10.1002\/eji.201847807","article-title":"The role of the gut microbiota and microbial metabolites in neuroinflammation","volume":"50","author":"Haase","year":"2020","journal-title":"Eur. J. Immunol."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Li, Q., Liu, H., Bai, C., Jiang, L., Su, C., Qin, X., Liu, T., and Gu, X. (2025). A high-calorie diet exacerbates lipopolysaccharide-induced pneumonia by promoting acetate-mediated macrophage polarization via the HDAC9\/10-HIF-1\u03b1-glycolysis axis. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1614768"},{"key":"ref_57","first-page":"S323","article-title":"The intestinal barrier in Parkinson\u2019s disease: Current state of knowledge","volume":"9","author":"Derkinderen","year":"2019","journal-title":"J. Park. Dis."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"137373","DOI":"10.1016\/j.ijbiomac.2024.137373","article-title":"Fucoidan ameliorates rotenone-induced Parkinsonism in mice by regulating the microbiota-gut-brain axis","volume":"283","author":"Yang","year":"2024","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2489","DOI":"10.1038\/s41423-021-00757-x","article-title":"The blood-brain barrier in systemic infection and inflammation","volume":"18","author":"Galea","year":"2021","journal-title":"Cell Mol. Immunol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1038\/s41593-024-01576-9","article-title":"Blood-brain barrier disruption and sustained systemic inflammation in individuals with long COVID-associated cognitive impairment","volume":"27","author":"Greene","year":"2024","journal-title":"Nat. Neurosci."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"e13955","DOI":"10.1111\/jfbc.13955","article-title":"Walnut oil alleviates LPS-induced intestinal epithelial cells injury by inhibiting TLR4\/MyD88\/NF-\u03baB pathway activation","volume":"45","author":"Miao","year":"2021","journal-title":"J. Food Biochem"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1094","DOI":"10.1007\/s11356-023-30708-0","article-title":"Curcumin alleviates traumatic brain injury induced by gas explosion through modulating gut microbiota and suppressing the LPS\/TLR4\/MyD88\/NF-\u03baB pathway","volume":"31","author":"Dong","year":"2024","journal-title":"Env. Sci. Pollut. Res. Int."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1186\/s12974-018-1308-0","article-title":"Ibrutinib suppresses LPS-induced neuroinflammatory responses in BV2 microglial cells and wild-type mice","volume":"15","author":"Nam","year":"2018","journal-title":"J. Neuroinflammation"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"155518","DOI":"10.1016\/j.phymed.2024.155518","article-title":"Gastrodin regulates the TLR4\/TRAF6\/NF-\u03baB pathway to reduce neuroinflammation and microglial activation in an AD model","volume":"128","author":"Wang","year":"2024","journal-title":"Phytomedicine"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1016\/j.tins.2017.04.001","article-title":"The Role of Astrocyte Dysfunction in Parkinson\u2019s Disease Pathogenesis","volume":"40","author":"Booth","year":"2017","journal-title":"Trends Neurosci."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Deacon, R.M. (2013). Measuring motor coordination in mice. J. Vis. Exp., e2609.","DOI":"10.3791\/2609"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Guyenet, S.J., Furrer, S.A., Damian, V.M., Baughan, T.D., and La Spada, A.R. (2010). A simple composite phenotype scoring system for evaluating mouse models of cerebellar ataxia. J. Vis. Exp., 1787.","DOI":"10.3791\/1787"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"112951","DOI":"10.1016\/j.jep.2020.112951","article-title":"Intestinal anti-inflammatory effects of fuzi-ganjiang herb pair against DSS-induced ulcerative colitis in mice","volume":"261","author":"Huang","year":"2020","journal-title":"J. Ethnopharmacol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1038\/ismej.2015.131","article-title":"Experimental insights into the importance of aquatic bacterial community composition to the degradation of dissolved organic matter","volume":"10","author":"Logue","year":"2016","journal-title":"ISME J."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1038\/s41587-019-0209-9","article-title":"Reproducible, interactive, scalable and extensible microbiome data science using QIIME 2","volume":"37","author":"Bolyen","year":"2019","journal-title":"Nat. Biotechnol."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Liu, B., Huang, L., Liu, Z., Pan, X., Cui, Z., Pan, J., and Xie, L. (2022). EasyMicroPlot: An efficient and convenient r package in microbiome downstream analysis and visualization for clinical study. Front. Genet., 12.","DOI":"10.3389\/fgene.2021.803627"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/15\/6573\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T04:26:23Z","timestamp":1784953583000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/15\/6573"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,23]]},"references-count":71,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["ijms27156573"],"URL":"https:\/\/doi.org\/10.3390\/ijms27156573","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,23]]}}}