{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T12:16:53Z","timestamp":1791289013247,"version":"4.3.0"},"reference-count":40,"publisher":"American Society for Clinical Investigation","issue":"13","license":[{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"vor","delay-in-days":49,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"crossref","award":["F30AG079577"],"award-info":[{"award-number":["F30AG079577"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000057","name":"National Institute on General Medical Sciences","doi-asserted-by":"crossref","award":["T32GM008152"],"award-info":[{"award-number":["T32GM008152"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"crossref","award":["5T32HL007909"],"award-info":[{"award-number":["5T32HL007909"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"crossref","award":["5T32AG020506"],"award-info":[{"award-number":["5T32AG020506"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"crossref","award":["R00 NS112458"],"award-info":[{"award-number":["R00 NS112458"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"crossref","award":["R01 AG078713"],"award-info":[{"award-number":["R01 AG078713"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Open Philanthropy\/Good Ventures Foundation","award":["Microbiome Consortium Grant"],"award-info":[{"award-number":["Microbiome Consortium Grant"]}]},{"DOI":"10.13039\/100007625","name":"Cure Alzheimer\u2019s Fund","doi-asserted-by":"crossref","award":["Microbiome Consortium Grant"],"award-info":[{"award-number":["Microbiome Consortium Grant"]}],"id":[{"id":"10.13039\/100007625","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Luminescence Foundation","award":["Microbiome grant"],"award-info":[{"award-number":["Microbiome grant"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,7,1]]},"abstract":"<jats:p>\n                    Accumulating evidence implicates the gut microbiome (GMB) in the pathogenesis and progression of Alzheimer\u2019s disease (AD). We recently showed that the GMB regulates reactive astrocytosis and A\u03b2 plaque accumulation in a male APPPS1-21 AD mouse model. Yet, the mechanism(s) by which GMB perturbation alters reactive astrocytosis in a manner that reduces A\u03b2 deposition remain unknown. Here, we performed metabolomics on plasma from mice treated with antibiotics (ABX) and identified a significant increase in plasma propionate, a gut-derived short-chain fatty acid, only in male mice. Administration of sodium propionate reduced reactive astrocytosis and A\u03b2 plaques in APPPS1-21 mice, phenocopying the ABX-induced phenotype. Astrocyte-specific RNA-Seq on ABX- and propionate-treated mice showed reduced expression of proinflammatory and increased expression of neurotrophic genes. Next, we performed flow cytometry experiments, in which we found that ABX and propionate decreased peripheral RAR-related orphan receptor-\u03b3\n                    <jats:sup>+<\/jats:sup>\n                    (Ror\u03b3t\n                    <jats:sup>+<\/jats:sup>\n                    ) CD4\n                    <jats:sup>+<\/jats:sup>\n                    (Th17) cells and IL-17 secretion, which positively correlated with reactive astrocytosis. Last, using an IL-17 mAb to deplete IL-17, we found that propionate reduced reactive astrocytosis and A\u03b2 plaques in an IL-17\u2013dependent manner. Together, these results suggest that gut-derived propionate regulates reactive astrocytosis and A\u03b2 amyloidosis by decreasing peripheral Th17 cells and IL-17 release. Thus, propionate treatment or strategies boosting propionate production may represent novel therapeutic strategies for the treatment of AD.\n                  <\/jats:p>","DOI":"10.1172\/jci180826","type":"journal-article","created":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T12:00:56Z","timestamp":1747137656000},"source":"Crossref","is-referenced-by-count":24,"title":["The gut microbiome controls reactive astrocytosis during A\u03b2 amyloidosis via propionate-mediated regulation of IL-17"],"prefix":"10.1172","volume":"135","author":[{"given":"Sidhanth","family":"Chandra","sequence":"first","affiliation":[{"name":"Ken and Ruth Davee Department of Neurology and"},{"name":"Medical Scientist Training Program, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jelena","family":"Popovic","sequence":"additional","affiliation":[{"name":"Ken and Ruth Davee Department of Neurology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naveen K.","family":"Singhal","sequence":"additional","affiliation":[{"name":"Ken and Ruth Davee Department of Neurology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elyse A.","family":"Watkins","sequence":"additional","affiliation":[{"name":"Ken and Ruth Davee Department of Neurology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hemraj B.","family":"Dodiya","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, University of Chicago, Chicago, Illinois, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian Q.","family":"Weigle","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, University of Chicago, Chicago, Illinois, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miranda A.","family":"Salvo","sequence":"additional","affiliation":[{"name":"Ken and Ruth Davee Department of Neurology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abhirami","family":"Ramakrishnan","sequence":"additional","affiliation":[{"name":"Ken and Ruth Davee Department of Neurology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhangying","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Surgery, Division of Trauma and Critical Care,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Watson","sequence":"additional","affiliation":[{"name":"Ken and Ruth Davee Department of Neurology and"},{"name":"Abrams Research Center on Neurogenomics,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aashutosh","family":"Shetti","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie","family":"Piehl","sequence":"additional","affiliation":[{"name":"Ken and Ruth Davee Department of Neurology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqiong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, University of Chicago, Chicago, Illinois, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leah","family":"Cuddy","sequence":"additional","affiliation":[{"name":"Ken and Ruth Davee Department of Neurology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8310-841X","authenticated-orcid":true,"given":"Katherine R.","family":"Sadleir","sequence":"additional","affiliation":[{"name":"Ken and Ruth Davee Department of Neurology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven J.","family":"Schwulst","sequence":"additional","affiliation":[{"name":"Department of Surgery, Division of Trauma and Critical Care,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Murali","family":"Prakriya","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Gate","sequence":"additional","affiliation":[{"name":"Ken and Ruth Davee Department of Neurology and"},{"name":"Abrams Research Center on Neurogenomics,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sangram S.","family":"Sisodia","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, University of Chicago, Chicago, Illinois, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Vassar","sequence":"additional","affiliation":[{"name":"Ken and Ruth Davee Department of Neurology and"},{"name":"Mesulam Center for Cognitive Neurology and Alzheimer\u2019s Disease, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2025,5,13]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.09.001"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-13601-y"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1038\/srep30028"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-11047-w"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20182386"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20200895"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1126\/science.add1236"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurot.2024.e00425"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-023-00635-2"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1038\/nature21029"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1111\/imr.13412"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-022-00631-9"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-023-00700-w"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2014.085"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1038\/nn.4030"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-64797-5"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2012.05.004"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2024.01.013"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.11.009"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-020-00988-5"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.15252\/embj.2022111515"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.3390\/nu13010228"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/j.aca.2019.04.021"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2021.10.010"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2023.114483"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.915218"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2015.09.007"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1186\/s12979-023-00397-x"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2117-15.2016"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-023-00595-7"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.59826"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1093\/ijnp\/pyw020"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.02.035"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1126\/science.1241165"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1038\/nature14052"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellimm.2005.11.002"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.181.6.3906"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2018-01-828996"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.14806\/ej.17.1.200"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btac166"}],"container-title":["Journal of Clinical Investigation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.jci.org\/articles\/view\/180826\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T17:16:37Z","timestamp":1779210997000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jci.org\/articles\/view\/180826"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,13]]},"references-count":40,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2025,5,13]]},"published-print":{"date-parts":[[2025,7,1]]}},"alternative-id":["10.1172\/JCI180826"],"URL":"https:\/\/doi.org\/10.1172\/jci180826","relation":{},"ISSN":["1558-8238"],"issn-type":[{"value":"1558-8238","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,13]]},"article-number":"e180826"}}