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Here, we show that a short, 7-d treatment of preweaned male mice with high-dose ABX is associated with reductions of A\u03b2 amyloidosis, plaque-localized microglia morphologies, and A\u03b2-associated degenerative changes at 9 wk of age in male mice only. More importantly, fecal microbiota transplantation (FMT) from transgenic (Tg) or WT male donors into ABX-treated male mice completely restored A\u03b2 amyloidosis, plaque-localized microglia morphologies, and A\u03b2-associated degenerative changes. Transcriptomic studies revealed significant differences between vehicle versus ABX-treated male mice and FMT from Tg mice into ABX-treated mice largely restored the transcriptome profiles to that of the Tg donor animals. Finally, colony-stimulating factor 1 receptor (CSF1R) inhibitor-mediated depletion of microglia in ABX-treated male mice failed to reduce cerebral A\u03b2 amyloidosis. Thus, microglia play a critical role in driving gut microbiome\u2013mediated alterations of cerebral A\u03b2 deposition.<\/jats:p>","DOI":"10.1084\/jem.20200895","type":"journal-article","created":{"date-parts":[[2021,10,15]],"date-time":"2021-10-15T02:33:24Z","timestamp":1634265204000},"update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":113,"title":["Gut microbiota\u2013driven brain A\u03b2 amyloidosis in mice requires microglia"],"prefix":"10.1084","volume":"219","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0908-0014","authenticated-orcid":true,"given":"Hemraj B.","family":"Dodiya","sequence":"first","affiliation":[{"name":"Department of Neurobiology, The University of Chicago, Chicago, IL 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6454-809X","authenticated-orcid":true,"given":"Holly L.","family":"Lutz","sequence":"additional","affiliation":[{"name":"Department of 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