{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T07:52:29Z","timestamp":1781164349460,"version":"3.54.1"},"reference-count":128,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2024,9,27]],"date-time":"2024-09-27T00:00:00Z","timestamp":1727395200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>Background: Alzheimer\u2019s disease is a progressive neurodegenerative disease characterized by structural changes in the brain, including hippocampal atrophy, cortical thinning, amyloid plaques, and tau tangles. Due to the aging of the global population, the burden of Alzheimer\u2019s disease is expected to increase, making the exploration of non-pharmacological interventions, such as physical exercise, an urgent priority. Results: There is emerging evidence that regular physical exercise may mitigate the structural and functional declines associated with Alzheimer\u2019s disease. The underlying mechanisms, however, remain poorly understood. Gut\u2013brain axis research is a promising area for further investigation. This system involves bidirectional communication between the gut microbiome and the brain. According to recent studies, the gut microbiome may influence brain health through modulating neuroinflammation, producing neuroactive compounds, and altering metabolic processes. Exercise has been shown to alter the composition of the gut microbiome, potentially impacting brain structure and function. In this review, we aim to synthesize current research on the relationship between physical exercise, structural brain changes in Alzheimer\u2019s disease, and the gut\u2013brain axis. Conclusions: In this study, we will investigate whether changes in the gut microbiome induced by physical exercise can mediate its neuroprotective effects, offering new insights into the prevention and treatment of Alzheimer\u2019s disease. By integrating findings from neuroimaging studies, clinical trials, and microbiome research, this review will highlight potential mechanisms. It will also identify key gaps in the literature. This will pave the way for future research directions.<\/jats:p>","DOI":"10.3390\/brainsci14100974","type":"journal-article","created":{"date-parts":[[2024,9,27]],"date-time":"2024-09-27T07:49:24Z","timestamp":1727423364000},"page":"974","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Physical Exercise and Mechanism Related to Alzheimer\u2019s Disease: Is Gut\u2013Brain Axis Involved?"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9451-8454","authenticated-orcid":false,"given":"Javier","family":"Sanchez-Martinez","sequence":"first","affiliation":[{"name":"Department of Physical Education and Sports, Faculty of Sport Sciences, Sport and Health University Research Institute (iMUDS), University of Granada, 18071 Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2493-9528","authenticated-orcid":false,"given":"Patricio","family":"Solis-Urra","sequence":"additional","affiliation":[{"name":"Department of Physical Education and Sports, Faculty of Sport Sciences, Sport and Health University Research Institute (iMUDS), University of Granada, 18071 Granada, Spain"},{"name":"Faculty of Education and Social Sciences, Universidad Andres Bello, Vi\u00f1a del Mar 8370134, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7186-3941","authenticated-orcid":false,"given":"Jorge","family":"Olivares-Arancibia","sequence":"additional","affiliation":[{"name":"AFySE Group, Research in Physical Activity and School Health, School of Physical Education, Faculty of Education, Universidad de Las Am\u00e9ricas, Santiago 7500975, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5171-9408","authenticated-orcid":false,"given":"Julio","family":"Plaza-Diaz","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology II, School of Pharmacy, Campus de Cartuja s\/n, University of Granada, 18071 Granada, Spain"},{"name":"Instituto de Investigaci\u00f3n Biosanitaria IBS.GRANADA, Complejo Hospitalario Universitario de Granada, 18014 Granada, Spain"},{"name":"Children\u2019s Hospital of Eastern Ontario Research Institute, Ottawa, ON K1H 8L1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/j.jalz.2018.02.018","article-title":"NIA-AA Research Framework: Toward a biological definition of Alzheimer\u2019s disease","volume":"14","author":"Jack","year":"2018","journal-title":"Alzheimers Dement."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1016\/S0140-6736(24)01296-0","article-title":"Dementia prevention, intervention, and care: 2024 report of the Lancet standing Commission","volume":"404","author":"Livingston","year":"2024","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1038\/s41392-024-01911-3","article-title":"Recent advances in Alzheimer\u2019s disease: Mechanisms, clinical trials and new drug development strategies","volume":"9","author":"Zhang","year":"2024","journal-title":"Signal Transduct. 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