Intermittent fasting protects against Alzheimer’s disease in mice by altering metabolism through remodeling of the gut microbiota
Abstract
Alzheimer's disease (AD) is the most common form of dementia without effective clinical treatment. Here, we show that intermittent fasting (IF) improves cognitive functions and AD-like pathology in a transgenic AD mouse model (5XFAD). IF alters gut microbial composition with a significant enrichment in probiotics such as Lactobacillus. The changes in the composition of the gut microbiota affect metabolic activities and metabolite production. Metabolomic profiling analysis of cecal contents revealed IF leads to a decreased carbohydrate metabolism (for example, glucose) and an increased abundance in amino acids (for example, sarcosine and dimethylglycine). Interestingly, we found that the administration of IF-elevated sarcosine or dimethylglycine mimics the protective effects of IF in 5XFAD mice, including the amelioration of cognitive decline, amyloid-β (Aβ) burden and glial overactivation. Our findings thus demonstrate an IF regimen is a potential approach to prevent AD progression, at least through the gut-microbiota-metabolites-brain axis, and constitutes an innovative AD therapeutic avenue.
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Butyric acid is significantly downregulated in cecal contents in response to intermittent fasting compared with mice fed ad libitum.
“However, metabolomic analysis of cecal contents found that butyric acid was significantly downregulated in response to intermittent fasting, as compared to mice that were fed ad libitum.312”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [312]
Intermittent fasting alleviates reactive microgliosis and astrogliosis, Aβ deposition, and cognitive impairment in 5xFAD mice by remodeling the microbiota-gut-brain axis.
“A recent study reported that intermittent fasting is effective in alleviating reactive microgliosis and astrogliosis, Aβ deposition, and cognitive impairment of 5xFAD mice by remodeling the microbiota–gut–brain axis.”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [312]
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Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases
Loh, J. S., Mak, W. Q., Tan, L. K. S., Ng, C. X., Chan, H. H., Yeow, S. H., Foo, J. B., Ong, Y. S., How, C. W., & Khaw, K. Y. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01743-1 · Cited by 1,193 · see citing works
- Authors
- Pan, R.-Y., Zhang, J., Wang, J., Wang, Y., Li, Z., Liao, Y., Liao, Y., Zhang, C., Liu, Z., Song, L., Yu, J., & Yuan, Z.
- Affiliations
- Institute of Basic Medical Sciences of the Chinese Academy of Medical Sciences (CN)
- Shanxi University of Traditional Chinese Medicine (CN)
- Beijing Radiation Center (CN)
- Corresponding author
- Pan, Rui-Yuan
- Yuan, Zengqiang
- ORCID
- Venue
- Nature Aging
- Published
- 2022-11-17
- Volume
- 2
- Issue
- 11
- Pages
- 1024-1039
- ISSN
- 2662-8465 (ISSN-L)
- OpenAlex
- W4309219012
- Cited by
- 107
- References
- 61
- Citations by year
- 2026: 34 · 2025: 34 · 2024: 25 · 2023: 12 · 2022: 2
- FWCI
- 11.29
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Nature Aging (publishedVersion)
- PubMed (publishedVersion)
- Funders
- China Postdoctoral Science Foundation (2020M683748)
- National Natural Science Foundation of China (81930029, 82230042)
- National Major Project of Support Program
- Topics
- Health Sciences › Medicine › Physiology › Dietary Effects on Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- intermittent fasting, Alzheimer's disease, gut microbiota, 5xFAD mice, sarcosine, dimethylglycine, cognitive decline, amyloid-beta, glial activation, Lactobacillus, carbohydrate metabolism, amino acids
- MeSH terms
- Gastrointestinal Microbiome, Intermittent Fasting, Alzheimer Disease, Animals, Mice, Transgenic, Sarcosine, Mice
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