{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T00:43:43Z","timestamp":1792197823096,"version":"4.4.0"},"reference-count":31,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,11,22]],"date-time":"2025-11-22T00:00:00Z","timestamp":1763769600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key R&D Program of China","doi-asserted-by":"publisher","award":["2023YFB3609103"],"award-info":[{"award-number":["2023YFB3609103"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["62175261"],"award-info":[{"award-number":["62175261"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences","award":["2021-I2M-1-058"],"award-info":[{"award-number":["2021-I2M-1-058"]}]},{"DOI":"10.13039\/501100006606","name":"Natural Science Foundation of Tianjin","doi-asserted-by":"publisher","award":["24JCZDJC00240"],"award-info":[{"award-number":["24JCZDJC00240"]}],"id":[{"id":"10.13039\/501100006606","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Alzheimer\u2019s disease (AD) is a major neurodegenerative disorder with limited effective and affordable therapies. Photobiomodulation (PBM) offers a safe, non-invasive treatment strategy, yet conventional transcranial PBM (tc-PBM) is restricted by low skull penetration. To overcome this limitation, gut microbiota-targeted PBM (gm-PBM) has been proposed to modulate the gut\u2013brain axis, though its efficacy and mechanisms remain unclear. Here, six-month-old APPswe\/PS1dE9 mice received gm-PBM or tc-PBM (810 nm, 25 mW\/cm2, 20 min\/day for 4 weeks). Behavioral testing revealed that both treatments improved spatial learning and memory, while histological analyses showed reduced amyloid-\u03b2 deposition and microglial shift toward an anti-inflammatory phenotype. Notably, gm-PBM specifically enriched short-chain fatty acid-producing bacteria, elevated propionate, butyrate, and secondary bile acids, and restored intestinal barrier integrity, whereas tc-PBM induced minimal microbiota changes. These findings suggest that gm-PBM confers neuroprotective effects comparable to or exceeding tc-PBM through modulation of the gut microbiota\u2013metabolism\u2013immune axis, highlighting its potential as a non-invasive and cost-effective therapeutic approach for AD.<\/jats:p>","DOI":"10.3390\/microorganisms13122659","type":"journal-article","created":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T10:24:17Z","timestamp":1763979857000},"page":"2659","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Gut Microbiota-Targeted Photobiomodulation Ameliorates Alzheimer\u2019s Pathology via the Gut\u2013Brain Axis: Comparable Efficacy to Transcranial Irradiation"],"prefix":"10.3390","volume":"13","author":[{"given":"Shisheng","family":"Cao","sequence":"first","affiliation":[{"name":"Integrative Regeneration Laboratory, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300192, China"},{"name":"Tianjin Key Laboratory of Neuromodulation and Neurorepair, Tianjin 300192, China"},{"name":"State Key Laboratory of Advanced Medical Materials and Devices, Tianjin 300192, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyu","family":"Shi","sequence":"additional","affiliation":[{"name":"Integrative Regeneration Laboratory, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300192, China"},{"name":"Tianjin Key Laboratory of Neuromodulation and Neurorepair, Tianjin 300192, China"},{"name":"State Key Laboratory of Advanced Medical Materials and Devices, Tianjin 300192, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongqiang","family":"Chen","sequence":"additional","affiliation":[{"name":"Integrative Regeneration Laboratory, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300192, China"},{"name":"Tianjin Key Laboratory of Neuromodulation and Neurorepair, Tianjin 300192, China"},{"name":"State Key Laboratory of Advanced Medical Materials and Devices, Tianjin 300192, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2455-3032","authenticated-orcid":false,"given":"Tiaotiao","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Biomedical Engineering and Technology, Tianjin Medical University, Tianjin 300070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiashen","family":"Hu","sequence":"additional","affiliation":[{"name":"Integrative Regeneration Laboratory, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300192, China"},{"name":"Tianjin Key Laboratory of Neuromodulation and Neurorepair, Tianjin 300192, China"},{"name":"State Key Laboratory of Advanced Medical Materials and Devices, Tianjin 300192, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxi","family":"Dong","sequence":"additional","affiliation":[{"name":"Integrative Regeneration Laboratory, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300192, China"},{"name":"Tianjin Key Laboratory of Neuromodulation and Neurorepair, Tianjin 300192, China"},{"name":"State Key Laboratory of Advanced Medical Materials and Devices, Tianjin 300192, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongli","family":"Chen","sequence":"additional","affiliation":[{"name":"Integrative Regeneration Laboratory, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300192, China"},{"name":"Tianjin Key Laboratory of Neuromodulation and Neurorepair, Tianjin 300192, China"},{"name":"State Key Laboratory of Advanced Medical Materials and Devices, Tianjin 300192, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianwu","family":"Dai","sequence":"additional","affiliation":[{"name":"Integrative Regeneration Laboratory, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300192, China"},{"name":"Tianjin Key Laboratory of Neuromodulation and Neurorepair, Tianjin 300192, China"},{"name":"State Key Laboratory of Advanced Medical Materials and Devices, Tianjin 300192, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huijuan","family":"Yin","sequence":"additional","affiliation":[{"name":"Integrative Regeneration Laboratory, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300192, China"},{"name":"Tianjin Key Laboratory of Neuromodulation and Neurorepair, Tianjin 300192, China"},{"name":"State Key Laboratory of Advanced Medical Materials and Devices, Tianjin 300192, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1016\/S0140-6736(20)32205-4","article-title":"Alzheimer\u2019s disease","volume":"397","author":"Scheltens","year":"2021","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1093\/procel\/pwae026","article-title":"Alzheimer\u2019s disease: Insights into pathology, molecular mechanisms, and therapy","volume":"16","author":"Zheng","year":"2025","journal-title":"Protein Cell"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/S1474-4422(20)30412-9","article-title":"APOE and Alzheimer\u2019s disease: Advances in genetics, pathophysiology, and therapeutic approaches","volume":"20","author":"Das","year":"2021","journal-title":"Lancet 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Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2205","DOI":"10.7150\/thno.70756","article-title":"Non-invasive photobiomodulation treatment in an Alzheimer Disease-like transgenic rat model","volume":"12","author":"Yang","year":"2022","journal-title":"Theranostics"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e2417380","DOI":"10.1002\/advs.202417380","article-title":"Photo-Biomodulation of the Hippocampus Using Near-Infrared Laser to Enhance Cognitive Function in Mice","volume":"12","author":"Pan","year":"2025","journal-title":"Adv. Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1186\/s13195-025-01714-w","article-title":"Photobiomodulation modulates mitochondrial energy metabolism and ameliorates neurological damage in an APP\/PS1 mousmodel of Alzheimer\u2019s disease","volume":"17","author":"Chen","year":"2025","journal-title":"Alzheimers Res. 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