{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:16:07Z","timestamp":1785402967492,"version":"3.56.0"},"reference-count":66,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T00:00:00Z","timestamp":1785369600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Key R&D Program of Shandong Province, China","award":["2024CXPT029"],"award-info":[{"award-number":["2024CXPT029"]}]},{"name":"Key R&D Program of Shandong Province, China","award":["2025CXPT011"],"award-info":[{"award-number":["2025CXPT011"]}]},{"DOI":"10.13039\/501100007129","name":"Shandong Provincial Natural Science Foundation","doi-asserted-by":"publisher","award":["ZR2024QH615"],"award-info":[{"award-number":["ZR2024QH615"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Shandong Laboratory Program","award":["SYS202205"],"award-info":[{"award-number":["SYS202205"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sci.","Brain Sciences"],"abstract":"<jats:p>Background: The Braak hypothesis proposes that \u03b1-synuclein (\u03b1-syn) pathology may originate in the gastrointestinal tract and propagate to the central nervous system along the gut\u2013brain axis; however, the precise propagation routes and the factors influencing this process remain controversial. Methods: A gut-originating Parkinson\u2019s disease model was established by injecting \u03b1-syn preformed fibrils (PFF) into the duodenal muscularis of C57BL\/6J and A53T transgenic mice. Phosphorylated \u03b1-synuclein (p-\u03b1-syn) pathology, motor behavior, and gut microbiota were assessed, with truncal vagotomy included to evaluate its association with gut-to-brain propagation. Results: In C57BL\/6J mice, at 4 months post-injection, p-\u03b1-syn deposition was observed in both the duodenal muscular layer and the striatum, accompanied by gut microbiota alterations and motor behavioral deficits. Truncal vagotomy was associated with reduced p-\u03b1-syn levels in the brain and alterations in the gut microbiota. In A53T transgenic mice, p-\u03b1-syn pathology and neurodegenerative changes were also observed following \u03b1-syn PFF injection, though the lack of a genetically matched wild-type control precludes definitive attribution of these phenotypes solely to the A53T transgene. Conclusions: These results align with the Braak hypothesis, showing that gut-derived p-\u03b1-syn pathology and associated functional impairments are intimately linked to vagal pathways during their propagation to the brain. Additionally, this gut-origin PD mouse model may serve as a useful tool for future mechanistic investigations.<\/jats:p>","DOI":"10.3390\/brainsci16080804","type":"journal-article","created":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T08:09:42Z","timestamp":1785398982000},"page":"804","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Duodenal \u03b1-Synuclein PFF Injection Induces Vagus-Related Gut-to-Brain Pathology in C57BL\/6J and A53T Transgenic Mice"],"prefix":"10.3390","volume":"16","author":[{"given":"Mengfei","family":"Wang","sequence":"first","affiliation":[{"name":"Key Laboratory of Marine Drugs, Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China"},{"name":"Shandong Laboratory of Yantai Drug Discovery, Bohai Rim Advanced Research Institute for Drug Discovery, Yantai 264117, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangqiang","family":"Sun","sequence":"additional","affiliation":[{"name":"Shandong Laboratory of Yantai Drug Discovery, Bohai Rim Advanced Research Institute for Drug Discovery, Yantai 264117, China"},{"name":"State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peifeng","family":"Wan","sequence":"additional","affiliation":[{"name":"Shandong Laboratory of Yantai Drug Discovery, Bohai Rim Advanced Research Institute for Drug Discovery, Yantai 264117, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zitong","family":"Wang","sequence":"additional","affiliation":[{"name":"Shandong Laboratory of Yantai Drug Discovery, Bohai Rim Advanced Research Institute for Drug Discovery, Yantai 264117, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-8256-0121","authenticated-orcid":false,"given":"Yali","family":"Nie","sequence":"additional","affiliation":[{"name":"Shandong Laboratory of Yantai Drug Discovery, Bohai Rim Advanced Research Institute for Drug Discovery, Yantai 264117, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2400-4351","authenticated-orcid":false,"given":"Hongchun","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meiyu","family":"Geng","sequence":"additional","affiliation":[{"name":"Shandong Laboratory of Yantai Drug Discovery, Bohai Rim Advanced Research Institute for Drug Discovery, Yantai 264117, China"},{"name":"State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Marine Drugs, Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China"},{"name":"Shandong Laboratory of Yantai Drug Discovery, Bohai Rim Advanced Research Institute for Drug Discovery, Yantai 264117, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-2075-3396","authenticated-orcid":false,"given":"Yu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Shandong Laboratory of Yantai Drug Discovery, Bohai Rim Advanced Research Institute for Drug Discovery, Yantai 264117, China"},{"name":"State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e464","DOI":"10.1016\/S2666-7568(24)00094-1","article-title":"Temporal trends in the prevalence of Parkinson\u2019s disease from 1980 to 2023: A systematic review and meta-analysis","volume":"5","author":"Zhu","year":"2024","journal-title":"Lancet Healthy Longev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1038\/s41582-024-01043-w","article-title":"\u03b1-Synuclein pathology as a target in neurodegenerative diseases","volume":"21","author":"Park","year":"2025","journal-title":"Nat. Rev. Neurol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"29739","DOI":"10.1074\/jbc.M600933200","article-title":"Phosphorylation of Ser-129 is the dominant pathological modification of \u03b1-synuclein in familial and sporadic Lewy body disease","volume":"281","author":"Anderson","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1038\/ncb748","article-title":"\u03b1-Synuclein is phosphorylated in synucleinopathy lesions","volume":"4","author":"Fujiwara","year":"2002","journal-title":"Nat. Cell Biol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1038\/s41598-022-04780-4","article-title":"Phosphorylation of endogenous \u03b1-synuclein induced by extracellular seeds initiates at the pre-synaptic region and spreads to the cell body","volume":"12","author":"Awa","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.neulet.2005.11.012","article-title":"Gastric \u03b1-synuclein immunoreactive inclusions in Meissner\u2019s and Auerbach\u2019s plexuses in cases staged for Parkinson\u2019s disease-related brain pathology","volume":"396","author":"Braak","year":"2006","journal-title":"Neurosci. Lett."},{"key":"ref_7","doi-asserted-by":"crossref","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":"ref_8","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1007\/s00702-002-0808-2","article-title":"Idiopathic Parkinson\u2019s disease: Possible routes by which vulnerable neuronal types may be subject to neuroinvasion by an unknown pathogen","volume":"110","author":"Braak","year":"2003","journal-title":"J. Neural Transm."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1126\/science.1227157","article-title":"Pathological \u03b1-synuclein transmission initiates Parkinson-like neurodegeneration in nontransgenic mice","volume":"338","author":"Luk","year":"2012","journal-title":"Science"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1038\/srep00898","article-title":"Environmental toxins trigger PD-like progression via increased alpha-synuclein release from enteric neurons in mice","volume":"2","author":"Schwarz","year":"2012","journal-title":"Sci. Rep."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.neuron.2011.08.033","article-title":"Exogenous \u03b1-synuclein fibrils induce Lewy body pathology leading to synaptic dysfunction and neuron death","volume":"72","author":"Luk","year":"2011","journal-title":"Neuron"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1016\/j.neuron.2019.05.035","article-title":"Transneuronal Propagation of Pathologic \u03b1-Synuclein from the Gut to the Brain Models Parkinson\u2019s Disease","volume":"103","author":"Kim","year":"2019","journal-title":"Neuron"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1007\/s00401-014-1343-6","article-title":"Direct evidence of Parkinson pathology spread from the gastrointestinal tract to the brain in rats","volume":"128","author":"Holmqvist","year":"2014","journal-title":"Acta Neuropathol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.nbd.2018.01.008","article-title":"Induction of alpha-synuclein pathology in the enteric nervous system of the rat and non-human primate results in gastrointestinal dysmotility and transient CNS pathology","volume":"112","author":"Manfredsson","year":"2018","journal-title":"Neurobiol. Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1186\/s13024-018-0257-5","article-title":"Inoculation of \u03b1-synuclein preformed fibrils into the mouse gastrointestinal tract induces Lewy body-like aggregates in the brainstem via the vagus nerve","volume":"13","author":"Uemura","year":"2018","journal-title":"Mol. Neurodegener."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1853","DOI":"10.1093\/brain\/awab061","article-title":"Ageing promotes pathological alpha-synuclein propagation and autonomic dysfunction in wild-type rats","volume":"144","author":"Ferreira","year":"2021","journal-title":"Brain J. Neurol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1462","DOI":"10.1093\/brain\/awaa096","article-title":"Bidirectional gut-to-brain and brain-to-gut propagation of synucleinopathy in non-human primates","volume":"143","author":"Arotcarena","year":"2020","journal-title":"Brain J. Neurol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1007\/s12035-025-05598-7","article-title":"Alterations of Gut Microbiota and Microbial Metabolites in Parkinson\u2019s Disease: A Systematic Review","volume":"63","author":"Davoody","year":"2025","journal-title":"Mol. Neurobiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1038\/s41531-021-00156-z","article-title":"Meta-analysis of the Parkinson\u2019s disease gut microbiome suggests alterations linked to intestinal inflammation","volume":"7","author":"Romano","year":"2021","journal-title":"npj Park. Dis."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1111\/cns.13990","article-title":"Gut bacterial profiles in Parkinson\u2019s disease: A systematic review","volume":"29","author":"Li","year":"2023","journal-title":"CNS Neurosci. Ther."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/S1474-4422(25)00382-5","article-title":"The gut microbiome, systemic inflammation, and autoimmunity in Parkinson\u2019s disease","volume":"25","author":"Zanetti","year":"2026","journal-title":"Lancet Neurol."},{"key":"ref_22","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_23","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1002\/nep3.70001","article-title":"The role of gut microbiota-derived metabolites in neuroinflammation","volume":"3","author":"Mu","year":"2025","journal-title":"Neuroprotection"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e144","DOI":"10.1017\/S003329172610436X","article-title":"Multimodal fusion of brain imaging and proteomics reveals a brain-body pathway linking depression and metabolic dysfunction","volume":"56","author":"Lian","year":"2026","journal-title":"Psychol. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1016\/j.jare.2025.05.034","article-title":"Beyond the Brain: Exploring the multi-organ axes in Parkinson\u2019s disease pathogenesis","volume":"80","author":"Liu","year":"2026","journal-title":"J. Adv. Res."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Kuang, N., Liu, Z., Yu, G., Wu, X., Becker, B., Fan, H., Peng, S., Zhang, K., Zhao, J., and Kang, J. (2023). Neurodevelopmental risk and adaptation as a model for comorbidity among internalizing and externalizing disorders: Genomics and cell-specific expression enriched morphometric study. BMC Med., 21.","DOI":"10.1186\/s12916-023-02920-9"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"104538","DOI":"10.1016\/j.phrs.2019.104538","article-title":"Caffeic acid reduces A53T \u03b1-synuclein by activating JNK\/Bcl-2-mediated autophagy in vitro and improves behaviour and protects dopaminergic neurons in a mouse model of Parkinson\u2019s disease","volume":"150","author":"Zhang","year":"2019","journal-title":"Pharmacol. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1177\/0192623315611501","article-title":"Reevaluation and Classification of Duodenal Lesions in B6C3F1 Mice and F344 Rats from 4 Studies of Hexavalent Chromium in Drinking Water","volume":"44","author":"Cullen","year":"2016","journal-title":"Toxicol. Pathol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"D1670","DOI":"10.1093\/nar\/gkae973","article-title":"Generic Diagramming Platform (GDP): A comprehensive database of high-quality biomedical graphics","volume":"53","author":"Jiang","year":"2025","journal-title":"Nucleic Acids Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1486","DOI":"10.1053\/j.gastro.2020.10.066","article-title":"The Microbiota-Gut-Brain Axis: From Motility to Mood","volume":"160","author":"Margolis","year":"2021","journal-title":"Gastroenterology"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"87","DOI":"10.5582\/bst.2024.01352","article-title":"Intestinal microbiota distribution and changes in different stages of Parkinson\u2019s disease: A meta-analysis, bioinformatics analysis and in vivo simulation","volume":"19","author":"Jiang","year":"2025","journal-title":"Biosci. Trends"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1016\/j.tibtech.2015.06.011","article-title":"Proteobacteria: Microbial signature of dysbiosis in gut microbiota","volume":"33","author":"Shin","year":"2015","journal-title":"Trends Biotechnol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.micpath.2016.02.005","article-title":"Akkermansia muciniphila and its role in regulating host functions","volume":"106","author":"Derrien","year":"2017","journal-title":"Microb. Pathog."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Yang, Y., Wang, H., Gu, Y., Wu, R., Qin, W., Chen, R., Fan, G., Xue, X., Lan, J., and Huang, Z. (2026). Bupleuri Radix Polysaccharides Alleviate MASLD by Regulating Muribaculaceae-Derived SCFAs in the Gut-Liver Axis. Int. J. Mol. Sci., 27.","DOI":"10.3390\/ijms27020637"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1016\/j.chom.2025.04.022","article-title":"Microbiota-derived urocanic acid triggered by tyrosine kinase inhibitors potentiates cancer immunotherapy efficacy","volume":"33","author":"Zhang","year":"2025","journal-title":"Cell Host Microbe"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1186\/s12967-025-07149-z","article-title":"Akkermansia muciniphila: A microbial guardian against oxidative stress-gut microbiota crosstalk and clinical prospects","volume":"23","author":"Ye","year":"2025","journal-title":"J. Transl. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"121420","DOI":"10.1016\/j.jep.2026.121420","article-title":"Ligilactobacillus murinus confers a dual benefit: Counteracting crotonis fructus-induced intestinal toxicity and synergizing with its processed form against ulcerative colitis","volume":"363","author":"Liu","year":"2026","journal-title":"J. Ethnopharmacol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2451088","DOI":"10.1080\/19490976.2025.2451088","article-title":"Limosilactobacillus reuteri\u2014A probiotic gut commensal with contextual impact on immunity","volume":"17","author":"Lee","year":"2025","journal-title":"Gut Microbes"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1038\/s41531-022-00312-z","article-title":"Plasma branched-chain and aromatic amino acids correlate with the gut microbiota and severity of Parkinson\u2019s disease","volume":"8","author":"Zhang","year":"2022","journal-title":"npj Park. Dis."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"8968","DOI":"10.1073\/pnas.132197599","article-title":"Human \u03b1-synuclein-harboring familial Parkinson\u2019s disease-linked Ala-53 \u2192 Thr mutation causes neurodegenerative disease with \u03b1-synuclein aggregation in transgenic mice","volume":"99","author":"Lee","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1016\/S0896-6273(02)00682-7","article-title":"Neuronal \u03b1-synucleinopathy with severe movement disorder in mice expressing A53T human \u03b1-synuclein","volume":"34","author":"Giasson","year":"2002","journal-title":"Neuron"},{"key":"ref_42","doi-asserted-by":"crossref","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":"Ferreira","year":"2019","journal-title":"Acta Neuropathol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1038\/s41593-020-0589-7","article-title":"Gut-seeded \u03b1-synuclein fibrils promote gut dysfunction and brain pathology specifically in aged mice","volume":"23","author":"Challis","year":"2020","journal-title":"Nat. Neurosci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"34885","DOI":"10.1074\/jbc.M110.148460","article-title":"Seeded aggregation and toxicity of \u03b1-synuclein and tau: Cellular models of neurodegenerative diseases","volume":"285","author":"Nonaka","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1038\/nature14547","article-title":"\u03b1-Synuclein strains cause distinct synucleinopathies after local and systemic administration","volume":"522","author":"Peelaerts","year":"2015","journal-title":"Nature"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"77","DOI":"10.5607\/en.2013.22.2.77","article-title":"Alpha-Synuclein Expression in Patients with Parkinson\u2019s Disease: A Clinician\u2019s Perspective","volume":"22","author":"Kim","year":"2013","journal-title":"Exp. Neurobiol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1002\/mds.23043","article-title":"Two Parkinson\u2019s disease patients with \u03b1-synuclein gene duplication and rapid cognitive decline","volume":"25","author":"Shin","year":"2010","journal-title":"Mov. Disord."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1536","DOI":"10.1002\/mdc3.13852","article-title":"Characterization of SNCA Multiplication in Parkinson\u2019s Disease: 2 New Cases and Evaluation of the Literature","volume":"10","author":"Duan","year":"2023","journal-title":"Mov. Disord. Clin. Pract."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1857","DOI":"10.1002\/mds.27527","article-title":"Genotype-phenotype relations for the Parkinson\u2019s disease genes SNCA, LRRK2, VPS35: MDSGene systematic review","volume":"33","author":"Trinh","year":"2018","journal-title":"Mov. Disord."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Book, A., Guella, I., Candido, T., Brice, A., Hattori, N., Jeon, B., and Farrer, M.J. (2018). A Meta-Analysis of \u03b1-Synuclein Multiplication in Familial Parkinsonism. Front. Neurol., 9.","DOI":"10.3389\/fneur.2018.01021"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1996","DOI":"10.1212\/WNL.0000000000003961","article-title":"Vagotomy and Parkinson disease: A Swedish register-based matched-cohort study","volume":"88","author":"Liu","year":"2017","journal-title":"Neurology"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1002\/ana.24448","article-title":"Vagotomy and subsequent risk of Parkinson\u2019s disease","volume":"78","author":"Svensson","year":"2015","journal-title":"Ann. Neurol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"3373","DOI":"10.1016\/j.celrep.2016.08.053","article-title":"Molecular and Biological Compatibility with Host Alpha-Synuclein Influences Fibril Pathogenicity","volume":"16","author":"Luk","year":"2016","journal-title":"Cell Rep."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1128","DOI":"10.1093\/brain\/awt037","article-title":"Prion-like spreading of pathological \u03b1-synuclein in brain","volume":"136","author":"Nonaka","year":"2013","journal-title":"Brain J. Neurol."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Hasegawa, S., Goto, S., Tsuji, H., Okuno, T., Asahara, T., Nomoto, K., Shibata, A., Fujisawa, Y., Minato, T., and Okamoto, A. (2015). Intestinal Dysbiosis and Lowered Serum Lipopolysaccharide-Binding Protein in Parkinson\u2019s Disease. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0142164"},{"key":"ref_56","first-page":"2339","article-title":"Exploring the Connection Between the Gut Microbiome and Parkinson\u2019s Disease Symptom Progression and Pathology: Implications for Supplementary Treatment Options","volume":"12","author":"Chan","year":"2022","journal-title":"J. Park. Dis."},{"key":"ref_57","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_58","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1016\/j.bbi.2024.04.034","article-title":"Alleviating effect of vagus nerve cutting in Salmonella-induced gut infections and anxiety-like behavior via enhancing microbiota-derived GABA","volume":"119","author":"Zou","year":"2024","journal-title":"Brain Behav. Immun."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"7875","DOI":"10.1007\/s12035-025-04741-8","article-title":"Enterococcus faecalis Exerts Neuroprotective Effects via the Vagus Nerve in a Mouse Model of Parkinson\u2019s Disease","volume":"62","author":"Shao","year":"2025","journal-title":"Mol. Neurobiol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"106440","DOI":"10.1016\/j.nbd.2024.106440","article-title":"Ameliorating effects of transcutaneous auricular vagus nerve stimulation on a mouse model of constipation-predominant irritable bowel syndrome","volume":"193","author":"Liu","year":"2024","journal-title":"Neurobiol. Dis."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1038\/s41398-020-00878-3","article-title":"A key role of the subdiaphragmatic vagus nerve in the depression-like phenotype and abnormal composition of gut microbiota in mice after lipopolysaccharide administration","volume":"10","author":"Zhang","year":"2020","journal-title":"Transl. Psychiatry"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.molimm.2026.05.003","article-title":"Branched-chain amino acids alleviate Parkinson\u2019s neurodegeneration via microbial propionate-dependent restoration of the PI3K\/Akt\/mTORC1 axis","volume":"195","author":"Mi","year":"2026","journal-title":"Mol. Immunol."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Zhang, X., Yu, H., and Feng, J. (2024). Emerging role of microglia in inter-cellular transmission of \u03b1-synuclein in Parkinson\u2019s disease. Front. Aging Neurosci., 16.","DOI":"10.3389\/fnagi.2024.1411104"},{"key":"ref_64","first-page":"1289","article-title":"Astrocytes and Alpha-Synuclein: Friend or Foe?","volume":"13","author":"Ozoran","year":"2023","journal-title":"J. Park. Dis."},{"key":"ref_65","first-page":"S105","article-title":"Microglia in Parkinson\u2019s Disease","volume":"12","author":"Stefanova","year":"2022","journal-title":"J. Park. Dis."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"107908","DOI":"10.1016\/j.phrs.2025.107908","article-title":"Exosome-mediated microglia-astrocyte interactions drive neuroinflammation in Parkinson\u2019s disease with Peli1 as a potential therapeutic target","volume":"219","author":"Guo","year":"2025","journal-title":"Pharmacol. Res."}],"container-title":["Brain Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3425\/16\/8\/804\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T08:38:04Z","timestamp":1785400684000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3425\/16\/8\/804"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,30]]},"references-count":66,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["brainsci16080804"],"URL":"https:\/\/doi.org\/10.3390\/brainsci16080804","relation":{},"ISSN":["2076-3425"],"issn-type":[{"value":"2076-3425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,30]]}}}