{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T23:41:52Z","timestamp":1792021312909,"version":"4.4.0"},"reference-count":61,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T00:00:00Z","timestamp":1773619200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Parkinson\u2019s disease (PD) is a multifactorial neurodegenerative disorder characterized by progressive motor and non-motor manifestations, including early gastrointestinal dysfunction. Growing evidence implicates the gut microbiota as an active modulator of host immune tone and neurodegenerative vulnerability, extending beyond descriptive taxonomic associations toward functional and metabolic mechanisms. PD-associated dysbiosis is consistently characterized by altered microbial functional capacity, including reduced short-chain fatty acid (SCFA) production, enrichment of pro-inflammatory metabolic traits, and sustained immune stimulation at the intestinal interface. These shifts promote chronic low-grade inflammation and intestinal barrier perturbations, creating conditions that may facilitate abnormal \u03b1-synuclein aggregation within the enteric nervous system. Current management predominantly relies on dopaminergic replacement and related symptomatic strategies, such as levodopa combinations, dopamine agonists, monoamine oxidase-B and catechol-O-methyltransferase (COMT) inhibitors, and device-aided therapies, which alleviate symptoms but do not halt underlying neurodegeneration or modify long-term disease course. These therapeutic limitations have intensified interest in upstream mechanisms that might be amenable to disease-modifying interventions, particularly those arising at the level of the gut microbiota and gut\u2013immune\u2013brain axis. This narrative review integrates clinical, metagenomic, metabolomic, and mechanistic evidence to propose a unified model in which microbiota-driven immune and metabolic perturbations may act as upstream drivers converging on \u03b1-synuclein pathology, neuroinflammation, and neurovascular dysfunction.<\/jats:p>","DOI":"10.3390\/microorganisms14030673","type":"journal-article","created":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T13:32:07Z","timestamp":1773667927000},"page":"673","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["The Gut Microbiota in Parkinson\u2019s Disease: Mechanistic Insights into Microbial\u2013Host Interactions"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-2651-0984","authenticated-orcid":false,"given":"Luis Enrique","family":"Guerrero-Torres","sequence":"first","affiliation":[{"name":"Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara, Guadalajara 44340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2120-1819","authenticated-orcid":false,"given":"Jes\u00fas Jonathan","family":"Garc\u00eda-Galindo","sequence":"additional","affiliation":[{"name":"Departamento de Fisiolog\u00eda, Instituto de Terap\u00e9utica Experimental y Cl\u00ednica, Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara, Guadalajara 44340, Mexico"},{"name":"Instituto de Terap\u00e9utica Experimental y Cl\u00ednica (INTEC), Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara, Guadalajara 44340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-5226-2258","authenticated-orcid":false,"given":"Mar\u00eda Fernanda","family":"G\u00f3mez-Galindo","sequence":"additional","affiliation":[{"name":"Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara, Guadalajara 44340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-6980-3846","authenticated-orcid":false,"given":"Diego Ian Rosales","family":"Delgado","sequence":"additional","affiliation":[{"name":"Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara, Guadalajara 44340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-8745-8455","authenticated-orcid":false,"given":"Cesar Eduardo","family":"Retolaza Carlos","sequence":"additional","affiliation":[{"name":"Departamento de Neurocirug\u00eda, Antiguo Hospital Civil de Guadalajara \u201cFray Antonio Alcalde\u201d, Guadalajara 44280, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9237-213X","authenticated-orcid":false,"given":"Daniel Osmar","family":"Su\u00e1rez-Rico","sequence":"additional","affiliation":[{"name":"Departamento de Fisiolog\u00eda, Instituto de Terap\u00e9utica Experimental y Cl\u00ednica, Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara, Guadalajara 44340, Mexico"},{"name":"Instituto de Terap\u00e9utica Experimental y Cl\u00ednica (INTEC), Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara, Guadalajara 44340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7892-9125","authenticated-orcid":false,"given":"Alberto","family":"Beltr\u00e1n-Ram\u00edrez","sequence":"additional","affiliation":[{"name":"Departamento de Fisiolog\u00eda, Instituto de Terap\u00e9utica Experimental y Cl\u00ednica, Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara, Guadalajara 44340, Mexico"},{"name":"Instituto de Terap\u00e9utica Experimental y Cl\u00ednica (INTEC), Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara, Guadalajara 44340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1540-9365","authenticated-orcid":false,"given":"Luis Ricardo","family":"Balleza Alejandri","sequence":"additional","affiliation":[{"name":"Instituto de Terap\u00e9utica Experimental y Cl\u00ednica (INTEC), Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara, Guadalajara 44340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1111\/cns.13549","article-title":"Quality of life in Parkinson\u2019s disease: A systematic review and meta-analysis of comparative studies","volume":"27","author":"Zhao","year":"2020","journal-title":"CNS Neurosci. 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