{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T23:36:47Z","timestamp":1790811407348,"version":"4.1.0"},"reference-count":40,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,6,9]],"date-time":"2025-06-09T00:00:00Z","timestamp":1749427200000},"content-version":"vor","delay-in-days":8,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>INTRODUCTION<\/jats:title><jats:p>Gut dysbiosis has been found to play a role in sporadic Alzheimer's disease (AD) but has not been explored in Down syndrome (DS), despite the strong relationship between DS and early AD. Here, we compared the gut microbiomes of 20 adults with DS, either cognitively stable or with mild cognitive impairment.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>DNA from stool samples was profiled using 16S rRNA sequencing.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Cognitive status was associated with a significant difference in overall microbiome composition (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.01) and with significant differences in the abundance of Bacteroidaceae, Enterobacteriaceae, and Christensenellaceae.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSION<\/jats:title><jats:p>Just as in sporadic AD, AD in DS is associated with gut dysbiosis. Our work suggests that this is an important area for future investigation, one that may provide a novel and important target for therapeutic intervention.<\/jats:p><\/jats:sec><jats:sec><jats:title>Highlights<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Alterations in the gut microbiome are present in adults with Down syndrome (DS) with mild cognitive impairment (MCI).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Increased taxa in DS\u2010MCI that contribute to inflammation and disrupt blood\u2013brain barrier.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Suggests a possible role of gut dysbiosis in Alzheimer's disease in adults with DS.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1002\/alz.70330","type":"journal-article","created":{"date-parts":[[2025,6,12]],"date-time":"2025-06-12T11:11:14Z","timestamp":1749726674000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Gut dysbiosis in Down syndrome: A potentially unexplored culprit for early Alzheimer's disease"],"prefix":"10.1002","volume":"21","author":[{"given":"Herminia Diana","family":"Rosas","sequence":"first","affiliation":[{"name":"Department of Neurology Massachusetts General Hospital, Harvard Medical School  Charlestown Massachusetts USA"},{"name":"Center for Neuroimaging of Aging and Neurodegenerative Diseases Massachusetts General Hospital, Harvard Medical School  Charlestown Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xochitl C.","family":"Morgan","sequence":"additional","affiliation":[{"name":"Microbiome Analysis Core Department of Biostatistics Harvard T.H. Chan School of Public Health  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiran","family":"Tao","sequence":"additional","affiliation":[{"name":"Department of Neurology Massachusetts General Hospital, Harvard Medical School  Charlestown Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florence","family":"Lai","sequence":"additional","affiliation":[{"name":"Department of Neurology Massachusetts General Hospital, Harvard Medical School  Charlestown Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathaniel D.","family":"Mercaldo","sequence":"additional","affiliation":[{"name":"Department of Neurology Massachusetts General Hospital, Harvard Medical School  Charlestown Massachusetts USA"},{"name":"Department of Radiology Massachusetts General Hospital, Harvard Medical School  Charlestown Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,6,9]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.20735"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.3233\/TRD-200090"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2012.93"},{"issue":"3","key":"e_1_2_8_5_1","first-page":"353","article-title":"Alzheimer's disease in Down syndrome","volume":"1","author":"Head E","year":"2012","journal-title":"Eur J Neurodegener Dis"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12112"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1072994"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1566067"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nucmedbio.2007.06.015"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-61962-y"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-017-0499-4"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/1742-2094-10-84"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aau3333"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.3233\/ADR-220029"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2018-317431"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-220106"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.53111"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s12276-023-01146-2"},{"issue":"1","key":"e_1_2_8_19_1","article-title":"The Alzheimer's Biomarker Consortium\u2010Down Syndrome: rationale and methodology","volume":"12","author":"Handen B","year":"2020","journal-title":"Alzheimers Dement"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkz569"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0061217"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu15092211"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2016.08.015"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2016.01544"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.73.9.5620-5627.2005"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-015-0434-1"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2017.00318"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12017-019-08547-5"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-13601-y"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep34477"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.683068"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2016.08.019"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abo2984"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/dneu.22713"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1006654"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1067484"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/imr.13296"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0501814102"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40168-018-0439-y"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-0897-4_9"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-020-02073-3"}],"container-title":["Alzheimer's &amp; 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