{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T06:42:43Z","timestamp":1776235363128,"version":"3.50.1"},"reference-count":115,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T00:00:00Z","timestamp":1776211200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Hubei Province Shizhen Talent Program","award":["Eweihan [2024]256"],"award-info":[{"award-number":["Eweihan [2024]256"]}]},{"name":"Innovation Project of the Key Discipline of Traditional Chinese Medicine in Hubei Province","award":["XK202405"],"award-info":[{"award-number":["XK202405"]}]},{"name":"Joint Innovation Fund of the Natural Science Foundation of Hubei Province","award":["JCZRLH202500947"],"award-info":[{"award-number":["JCZRLH202500947"]}]},{"name":"Joint Innovation Fund of the Natural Science Foundation of Hubei Province","award":["2024AFD298"],"award-info":[{"award-number":["2024AFD298"]}]},{"name":"Youth Program of the National Natural Science Foundation of China","award":["82405575"],"award-info":[{"award-number":["82405575"]}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging Neurosci."],"abstract":"<jats:p>Gut microbiota dysbiosis contributes to the development of Alzheimer\u2019s disease (AD) through gut-brain axis mediated processes, including neuroinflammation, \u03b2-amyloid (A\u03b2) accumulation, tau hyperphosphorylation, disruption of the blood-brain barrier, and progressive cognitive impairment. Exercise, as a non-pharmacological intervention, has been shown to counteract these pathological features by enhancing the production of neuroprotective short-chain fatty acids, reducing systemic and central inflammation, strengthening intestinal barrier integrity, and promoting neuroplasticity. This review integrates preclinical and clinical findings to evaluate the therapeutic potential of exercise in improving cognitive function and attenuating AD pathology, and summarizes key biological mechanisms involving microbiota modulation, short-chain fatty acid (SCFA) metabolism, immune regulation, and gut-brain communication. Current challenges include the limited number of human clinical trials, variability in intervention outcomes, individual differences in responsiveness, and dependence on exercise duration and intensity. Advancing this field will require rigorous longitudinal randomized controlled studies, multimodal therapeutic strategies, and personalized exercise protocols informed by baseline microbiota profiles and genetic risk factors. Although exercise is not curative, it represents an essential component of multitarget interventions and may delay AD progression through modulation of the gut-brain axis.<\/jats:p>","DOI":"10.3389\/fnagi.2026.1765016","type":"journal-article","created":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T05:42:13Z","timestamp":1776231733000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Exercise-based modulation of the gut-brain axis: a new direction for neurorehabilitation in Alzheimer\u2019s disease"],"prefix":"10.3389","volume":"18","author":[{"given":"ZhaoXie","family":"Yu","sequence":"first","affiliation":[{"name":"College of Acupuncture-Moxibustion and Orthopaedics, Hubei University of Chinese Medicine","place":["Wuhan, China"]},{"name":"Hubei Shizhen Laboratory","place":["Wuhan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"RongQi","family":"Yao","sequence":"additional","affiliation":[{"name":"School of Physical Education and Health, Hubei University of Chinese Medicine","place":["Wuhan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"YaNan","family":"Li","sequence":"additional","affiliation":[{"name":"College of Acupuncture-Moxibustion and Orthopaedics, Hubei University of Chinese Medicine","place":["Wuhan, China"]},{"name":"Hubei Shizhen Laboratory","place":["Wuhan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"HanZhang","family":"Li","sequence":"additional","affiliation":[{"name":"School of Nursing, Hubei University of Chinese Medicine","place":["Wuhan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Feng","family":"Shen","sequence":"additional","affiliation":[{"name":"College of Acupuncture-Moxibustion and Orthopaedics, Hubei University of Chinese Medicine","place":["Wuhan, China"]},{"name":"Hubei Shizhen Laboratory","place":["Wuhan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"YanChun","family":"Wang","sequence":"additional","affiliation":[{"name":"Hubei Shizhen Laboratory","place":["Wuhan, China"]},{"name":"College of Chinese Medicine, Hubei University of Chinese Medicine","place":["Wuhan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yao","family":"Wang","sequence":"additional","affiliation":[{"name":"Hubei Shizhen Laboratory","place":["Wuhan, China"]},{"name":"School of Physical Education and Health, Hubei University of Chinese Medicine","place":["Wuhan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,15]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"4217","DOI":"10.1523\/JNEUROSCI.0496-05.2005","article-title":"Voluntary exercise decreases amyloid load in a transgenic model of Alzheimer\u2019s disease","volume":"25","author":"Adlard","year":"2005","journal-title":"J. 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