{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T05:18:01Z","timestamp":1787807881935,"version":"build-2784847793"},"reference-count":112,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T00:00:00Z","timestamp":1787788800000},"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. Med."],"abstract":"<jats:p>The gut\u2013brain axis constitutes a bidirectional communication network that links the gut microbiota with the central nervous system (CNS) and plays a pivotal role in regulating neuroinflammation. Memory T cells, as central orchestrators of adaptive immunity, undergo differentiation, trafficking, and functional reprogramming within the gut microenvironment. This process establishes a novel framework for understanding the pathogenesis of neuroinflammatory disorders. In this review, we summarize the physiological crosstalk within the gut\u2013brain axis and outline the functional characteristics of memory T cell subsets. Furthermore, we elucidate how the gut microbiota shapes memory T cell phenotypes, decipher the molecular pathways that govern their trafficking across the gut\u2013brain barrier, and detail three key mechanisms by which these cells drive neuroinflammation: molecular mimicry, bystander activation that amplifies inflammatory cascades, and persistent epigenetic imprinting that directs functional polarization. Additionally, we consolidate diagnostic evidence from gut microbiota profiling, memory T cell phenotyping, and gut\u2013brain axis-specific biomarkers. Finally, we evaluate current therapeutic advances and intervention strategies targeting the gut microbiota and memory T cells.<\/jats:p>","DOI":"10.3389\/fmed.2026.1824172","type":"journal-article","created":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T04:27:14Z","timestamp":1787804834000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Gut-derived memory T cells: key mediators of neuroinflammation via the gut-brain axis"],"prefix":"10.3389","volume":"13","author":[{"given":"Peiyi","family":"Liang","sequence":"first","affiliation":[{"name":"Department of Medical Research Center, Second Hospital of Jilin University","place":["Changchun, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Songbai","family":"Xu","sequence":"additional","affiliation":[{"name":"First Clinical Hospital of Jilin Provincial Academy of Chinese Medical Sciences","place":["Changchun, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiying","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Second Hospital of Jilin University","place":["Changchun, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianchuang","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Second Hospital of Jilin University","place":["Changchun, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yicun","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Medical Research Center, Second Hospital of Jilin University","place":["Changchun, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,27]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"1439125","DOI":"10.3389\/fneur.2024.1439125","article-title":"The role of inflammation in 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