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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.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Here, we show that dietary inulin supplementation synergized with AD progression to specifically increase the abundance of <jats:italic>Akkermansia muciniphila<\/jats:italic> in gut microbiome of 5\u2009\u00d7\u2009Familial 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-\u03b2 plaque burden and alleviates microgliosis in the forebrain region, without affecting the spatial learning and memory.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>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.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/s12915-025-02230-x","type":"journal-article","created":{"date-parts":[[2025,5,9]],"date-time":"2025-05-09T14:13:35Z","timestamp":1746800015000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["A single-cell transcriptomic atlas of all cell types in the brain of 5xFAD Alzheimer mice in response to dietary inulin supplementation"],"prefix":"10.1186","volume":"23","author":[{"given":"Xiaoyan","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Houyu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhou","family":"Wan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuetong","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos F.","family":"Ib\u00e1\u00f1ez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,5,9]]},"reference":[{"issue":"6","key":"2230_CR1","doi-asserted-by":"publisher","first-page":"595","DOI":"10.15252\/emmm.201606210","volume":"8","author":"DJ Selkoe","year":"2016","unstructured":"Selkoe DJ, Hardy J. 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