A single-cell transcriptomic atlas of all cell types in the brain of 5xFAD Alzheimer mice in response to dietary inulin supplementation
Abstract Background Alzheimer’s disease (AD) is a progressive neurodegenerative disease that is a major threat to the aging population. Due to lack of effective therapy, preventive treatments are important strategies to limit AD onset and progression, of which dietary regimes have been implicated as...
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BMC
2025-05-01
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| Online Access: | https://doi.org/10.1186/s12915-025-02230-x |
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| author | Xiaoyan Wang Houyu Zhang Zhou Wan Xuetong Li Carlos F. Ibáñez Meng Xie |
| author_facet | Xiaoyan Wang Houyu Zhang Zhou Wan Xuetong Li Carlos F. Ibáñez Meng Xie |
| author_sort | Xiaoyan Wang |
| collection | DOAJ |
| description | Abstract Background Alzheimer’s disease (AD) is a progressive neurodegenerative disease that is a major threat to the aging population. Due to lack of effective therapy, preventive treatments are important strategies to limit AD onset and progression, of which dietary regimes have been implicated as a key factor. Diet with high fiber content is known to have beneficial effects on cognitive decline in AD. However, a global survey on microbiome and brain cell dynamics in response to high fiber intake at single-cell resolution in AD mouse models is still missing. Results Here, we show that dietary inulin supplementation synergized with AD progression to specifically increase the abundance of Akkermansia muciniphila in gut microbiome of 5 × Familial AD (FAD) mice. By performing single-nucleus RNA sequencing on different regions of the whole brain with three independent biological replicates, we reveal region-specific changes in the proportion of neuron, astrocyte, and granule cell subpopulations upon inulin supplementation in 5xFAD mice. In addition, we find that astrocytes have more pronounced region-specific diversity than microglia. Intriguingly, such dietary change reduces amyloid-β plaque burden and alleviates microgliosis in the forebrain region, without affecting the spatial learning and memory. Conclusions These results provide a comprehensive overview on the transcriptomic changes in individual cells of the entire mouse brain in response to high fiber intake and a resourceful foundation for future mechanistic studies on the influence of diet and gut microbiome on the brain during neurodegeneration. |
| format | Article |
| id | doaj-art-e8ff869771fd4afa8450058d608f573f |
| institution | Kabale University |
| issn | 1741-7007 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Biology |
| spelling | doaj-art-e8ff869771fd4afa8450058d608f573f2025-08-20T03:53:13ZengBMCBMC Biology1741-70072025-05-0123112510.1186/s12915-025-02230-xA single-cell transcriptomic atlas of all cell types in the brain of 5xFAD Alzheimer mice in response to dietary inulin supplementationXiaoyan Wang0Houyu Zhang1Zhou Wan2Xuetong Li3Carlos F. Ibáñez4Meng Xie5School of Basic Medical Sciences, Capital Medical UniversityChinese Institute for Brain Research, Zhongguancun Life Science ParkSchool of Life Sciences, Peking UniversitySchool of Life Sciences, Peking UniversitySchool of Basic Medical Sciences, Capital Medical UniversityPeking-Tsinghua Center for Life SciencesAbstract Background Alzheimer’s disease (AD) is a progressive neurodegenerative disease that is a major threat to the aging population. Due to lack of effective therapy, preventive treatments are important strategies to limit AD onset and progression, of which dietary regimes have been implicated as a key factor. Diet with high fiber content is known to have beneficial effects on cognitive decline in AD. However, a global survey on microbiome and brain cell dynamics in response to high fiber intake at single-cell resolution in AD mouse models is still missing. Results Here, we show that dietary inulin supplementation synergized with AD progression to specifically increase the abundance of Akkermansia muciniphila in gut microbiome of 5 × Familial AD (FAD) mice. By performing single-nucleus RNA sequencing on different regions of the whole brain with three independent biological replicates, we reveal region-specific changes in the proportion of neuron, astrocyte, and granule cell subpopulations upon inulin supplementation in 5xFAD mice. In addition, we find that astrocytes have more pronounced region-specific diversity than microglia. Intriguingly, such dietary change reduces amyloid-β plaque burden and alleviates microgliosis in the forebrain region, without affecting the spatial learning and memory. Conclusions These results provide a comprehensive overview on the transcriptomic changes in individual cells of the entire mouse brain in response to high fiber intake and a resourceful foundation for future mechanistic studies on the influence of diet and gut microbiome on the brain during neurodegeneration.https://doi.org/10.1186/s12915-025-02230-xAlzheimer’s diseaseSingle-nucleus RNA sequencingInulinBrain |
| spellingShingle | Xiaoyan Wang Houyu Zhang Zhou Wan Xuetong Li Carlos F. Ibáñez Meng Xie A single-cell transcriptomic atlas of all cell types in the brain of 5xFAD Alzheimer mice in response to dietary inulin supplementation BMC Biology Alzheimer’s disease Single-nucleus RNA sequencing Inulin Brain |
| title | A single-cell transcriptomic atlas of all cell types in the brain of 5xFAD Alzheimer mice in response to dietary inulin supplementation |
| title_full | A single-cell transcriptomic atlas of all cell types in the brain of 5xFAD Alzheimer mice in response to dietary inulin supplementation |
| title_fullStr | A single-cell transcriptomic atlas of all cell types in the brain of 5xFAD Alzheimer mice in response to dietary inulin supplementation |
| title_full_unstemmed | A single-cell transcriptomic atlas of all cell types in the brain of 5xFAD Alzheimer mice in response to dietary inulin supplementation |
| title_short | A single-cell transcriptomic atlas of all cell types in the brain of 5xFAD Alzheimer mice in response to dietary inulin supplementation |
| title_sort | single cell transcriptomic atlas of all cell types in the brain of 5xfad alzheimer mice in response to dietary inulin supplementation |
| topic | Alzheimer’s disease Single-nucleus RNA sequencing Inulin Brain |
| url | https://doi.org/10.1186/s12915-025-02230-x |
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