Transplantation of gut microbiota derived from Alzheimer’s disease mouse model impairs memory function and neurogenesis in C57BL/6 mice
Abstract
Alzheimer's disease (AD) is a neurodegenerative disease that causes memory and cognitive decline. Although many studies have attempted to clarify the causes of AD occurrence, it is not clearly understood. Recently, the emerging role of the gut microbiota in neurodegenerative diseases, including AD, has received much attention. The gut microbiota composition of AD patients and AD mouse models is different from that of healthy controls, and these changes may affect the brain environment. However, the specific mechanisms by which gut microbiota that influence memory decline are currently unclear. In this study, we performed fecal microbiota transplantation (FMT) to clarify the role of 5xFAD mouse-derived microbiota in memory decline. We observed that FMT from 5xFAD mice into normal C57BL/6 mice (5xFAD-FMT) decreased adult hippocampal neurogenesis and brain-derived neurotrophic factor expression and increased p21 expression, resulting in memory impairment. Microglia in the hippocampus of the 5xFAD-FMT mice were activated, which caused the elevation of pro-inflammatory cytokines (tumor necrosis factor-α and interleukin-1β). Moreover, we observed that pro-inflammatory cytokines increased in the colon and plasma of 5xFAD-FMT mice. The gut microbiota composition of the 5xFAD-FMT mice was different from that of the control mice or wild type-FMT mice. Collectively, 5xFAD mouse-derived microbiota decreased neurogenesis by increasing colonic inflammation, thereby contributing to memory l…
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Fecal microbiota transplantation studies demonstrate that AD pathological features can be largely transferred to a healthy host via the gut microbiota, indicating a possible causal role of commensal microbes in AD.
“Fecal microbiota transplantation studies demonstrate that AD pathological features can be largely transferred to a healthy host via the gut microbiota, indicating a possible causal role of commensal microbes in AD.”
From What would it take to prove that a chronic infection is a causal agent in Alzheimer’s disease? (2025) · cites this paper as [99]
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- Authors
- Kim, N., Jeon, S. H., Ju, I. G., Gee, M. S., Do, J., Oh, M. S., & Lee, J. K.
- Affiliations
- Kyung Hee University (KR)
- Corresponding author
- Oh, Myung Sook
- Lee, Jong Kil
- Venue
- Brain, Behavior, and Immunity
- Publisher
- Elsevier BV
- Published
- 2021-11
- Volume
- 98
- Pages
- 357-365
- ISSN
- 0889-1591 (ISSN-L)
- OpenAlex
- W3197935078
- Cited by
- 231
- References
- 11
- Citations by year
- 2026: 35 · 2025: 45 · 2024: 62 · 2023: 61 · 2022: 27 · 2021: 1
- FWCI
- 11.92
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Brain Behavior and Immunity (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministry of Science, ICT and Future Planning (NRF-2017R1A5A2014768, NRF-2021R1F1A1045522)
- National Research Foundation of Korea
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- Alzheimer's disease, gut microbiota, fecal microbiota transplantation, 5xFAD mice, memory impairment, adult hippocampal neurogenesis, brain-derived neurotrophic factor, p21, microglial activation, inflammatory cytokines, colonic inflammation, dysbiosis, neuroinflammation
- MeSH terms
- Gastrointestinal Microbiome, Alzheimer Disease, Animals, Humans, Mice, Inbred C57BL, Neurodegenerative Diseases, Mice, Neurogenesis
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