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Microorganisms
Volume 13
Issue 12
10.3390/microorganisms13122659
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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

Gut Microbiota-Targeted Photobiomodulation Ameliorates Alzheimer’s Pathology via the Gut–Brain Axis: Comparable Efficacy to Transcranial Irradiation

by
Shisheng Cao
1,2,3,†,
Xinyu Shi
1,2,3,†,
Yongqiang Chen
1,2,3,
Tiaotiao Liu
4,
Jiashen Hu
1,2,3,
Xiaoxi Dong
1,2,3,*,
Hongli Chen
1,2,3,
Jianwu Dai
1,2,3 and
Huijuan Yin
1,2,3,*
1
Integrative Regeneration Laboratory, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300192, China
2
Tianjin Key Laboratory of Neuromodulation and Neurorepair, Tianjin 300192, China
3
State Key Laboratory of Advanced Medical Materials and Devices, Tianjin 300192, China
4
School of Biomedical Engineering and Technology, Tianjin Medical University, Tianjin 300070, China
*
Authors to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Microorganisms 2025, 13(12), 2659; https://doi.org/10.3390/microorganisms13122659 (registering DOI)
Submission received: 22 October 2025 / Revised: 17 November 2025 / Accepted: 20 November 2025 / Published: 22 November 2025
(This article belongs to the Special Issue Gut Microbiome in Homeostasis and Disease, 3rd Edition)
Versions Notes

Abstract

Alzheimer’s 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–brain 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-β 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–metabolism–immune axis, highlighting its potential as a non-invasive and cost-effective therapeutic approach for AD.
Keywords: Alzheimer disease; light intervention; photobiomodulation; gut–brain axis Alzheimer disease; light intervention; photobiomodulation; gut–brain axis

Share and Cite

MDPI and ACS Style

Cao, S.; Shi, X.; Chen, Y.; Liu, T.; Hu, J.; Dong, X.; Chen, H.; Dai, J.; Yin, H. Gut Microbiota-Targeted Photobiomodulation Ameliorates Alzheimer’s Pathology via the Gut–Brain Axis: Comparable Efficacy to Transcranial Irradiation. Microorganisms 2025, 13, 2659. https://doi.org/10.3390/microorganisms13122659

AMA Style

Cao S, Shi X, Chen Y, Liu T, Hu J, Dong X, Chen H, Dai J, Yin H. Gut Microbiota-Targeted Photobiomodulation Ameliorates Alzheimer’s Pathology via the Gut–Brain Axis: Comparable Efficacy to Transcranial Irradiation. Microorganisms. 2025; 13(12):2659. https://doi.org/10.3390/microorganisms13122659

Chicago/Turabian Style

Cao, Shisheng, Xinyu Shi, Yongqiang Chen, Tiaotiao Liu, Jiashen Hu, Xiaoxi Dong, Hongli Chen, Jianwu Dai, and Huijuan Yin. 2025. "Gut Microbiota-Targeted Photobiomodulation Ameliorates Alzheimer’s Pathology via the Gut–Brain Axis: Comparable Efficacy to Transcranial Irradiation" Microorganisms 13, no. 12: 2659. https://doi.org/10.3390/microorganisms13122659

APA Style

Cao, S., Shi, X., Chen, Y., Liu, T., Hu, J., Dong, X., Chen, H., Dai, J., & Yin, H. (2025). Gut Microbiota-Targeted Photobiomodulation Ameliorates Alzheimer’s Pathology via the Gut–Brain Axis: Comparable Efficacy to Transcranial Irradiation. Microorganisms, 13(12), 2659. https://doi.org/10.3390/microorganisms13122659

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