{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T13:00:51Z","timestamp":1790168451922,"version":"4.1.0"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T00:00:00Z","timestamp":1790121600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging Neurosci."],"abstract":"<jats:p>Parkinson\u2019s disease (PD) is increasingly understood as a multisystem disorder in which gastrointestinal dysfunction, immune remodeling, protein aggregation, and central neurodegeneration interact across the disease course. Although gut microbiota alterations are repeatedly reported in PD, taxonomic differences alone do not explain how peripheral ecological signals acquire neurological relevance. This review therefore focuses on immune translation: the processes through which dysbiosis, microbial metabolites, intestinal barrier stress, and mucosal inflammation may reshape peripheral immunity and lower the threshold for central neuroinflammatory responses. Particular attention is given to trained immunity as a mechanistic framework that may connect repeated low-grade gut-derived stimulation with persistent innate immune reprogramming. Direct evidence that trained immunity drives PD remains limited; the concept is presented as a testable bridge rather than an established causal pathway. We integrate this framework with age-related immunosenescence and inflammaging, enteric nervous system vulnerability, vagal communication, alpha-synuclein pathology, blood\u2013brain barrier signaling, and microglial priming. Human microbiome studies, Parkinsonian animal models, LPS-based innate immune-memory paradigms, and emerging intervention trials are considered according to their evidentiary level and major confounders, including constipation, diet, medication exposure, geography, and disease stage. The resulting model accommodates body-first, brain-first, and mixed trajectories rather than assigning a universal gut origin to PD. Therapeutically, the evidence supports a shift from nonspecific microbiome normalization toward mechanism-matched strategies that combine ecological, immune, metabolic, and clinical biomarkers. Longitudinal prodromal cohorts and integrated multi-omics with immune phenotyping will be essential to determine whether gut-brain immune signatures identify causal pathways, progression markers, or treatment-responsive subgroups.<\/jats:p>","DOI":"10.3389\/fnagi.2026.1973833","type":"journal-article","created":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T12:03:41Z","timestamp":1790165021000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Gut-brain immune dysregulation in Parkinson\u2019s disease: a hypothesis-forming narrative review of trained immunity"],"prefix":"10.3389","volume":"18","author":[{"given":"Mingke","family":"Tang","sequence":"first","affiliation":[{"name":"Heilongjiang Academy of Traditional Chinese Medicine","place":["Harbin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingxian","family":"Li","sequence":"additional","affiliation":[{"name":"Heilongjiang Academy of Traditional Chinese Medicine","place":["Harbin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuanzhang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Heilongjiang Academy of Traditional Chinese Medicine","place":["Harbin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruoxin","family":"Tu","sequence":"additional","affiliation":[{"name":"Heilongjiang University of Chinese Medicine","place":["Harbin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shun","family":"Wang","sequence":"additional","affiliation":[{"name":"Heilongjiang University of Chinese Medicine","place":["Harbin, China"]},{"name":"Heilongjiang University of Chinese Medicine Affiliated Second Hospital","place":["Harbin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,23]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"691","DOI":"10.1016\/j.ebiom.2019.05.064","article-title":"Gut microbiota in Parkinson's disease: temporal stability and relations to disease progression","volume":"44","author":"Aho","year":"2019","journal-title":"EBioMedicine"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1007\/s11910-022-01207-5","article-title":"Neurodegeneration and neuroinflammation in Parkinson's disease: a self-sustained loop","volume":"22","author":"Arena","year":"2022","journal-title":"Curr. 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