{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T05:40:29Z","timestamp":1793252429097,"version":"4.5.0"},"reference-count":40,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T00:00:00Z","timestamp":1761782400000},"content-version":"vor","delay-in-days":29,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006388","name":"H\u00f4pitaux Universitaires de Gen\u00e8ve","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006388","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003246","name":"Nederlandse Organisatie voor Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["175.2019.032"],"award-info":[{"award-number":["175.2019.032"]}],"id":[{"id":"10.13039\/501100003246","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp; Dementia"],"published-print":{"date-parts":[[2025,10]]},"abstract":"Abstract<\/jats:title>\n \n INTRODUCTION<\/jats:title>\n Gut\u2010microbiota dysbiosis has been linked to cognitive decline. Given its role in metabolism, immunity, and environmental interactions, broader molecular signaling alterations are likely.<\/jats:p>\n <\/jats:sec>\n \n METHODS<\/jats:title>\n We analyzed gut microbiota composition, plasma and fecal metabolites, and inflammatory cytokines across cognitive stages, from healthy controls to dementia.<\/jats:p>\n <\/jats:sec>\n \n RESULTS<\/jats:title>\n \n Alpha diversity declined with increasing cognitive impairment severity. Short\u2010chain fatty acid\u2013producing Firmicutes and Bacteroidota decreased from 76% and 17% in controls to 59% and 11% in dementia, respectively. Proteobacteria (e.g., Escherichia\u2010Shigella) rose from\u00a0<\u00a02% to 4%, and Verrucomicrobiota from 3% to 11%. Despite overall Firmicutes decline,\n Ruminococcus gnavus<\/jats:italic>\n , a mucus\u2010degrading species, increased in dementia. These shifts correlated with elevated plasma cytokines, suggesting a link between gut dysbiosis and systemic inflammation. Bacteria\u2010associated metabolites, including bile acids, trimethylamine N\u2010oxide, oxylipins, sugars, and fatty acids were significantly altered. Changes were seen as early as subjective cognitive decline.\n <\/jats:p>\n <\/jats:sec>\n \n DISCUSSION<\/jats:title>\n Larger studies are needed to validate these findings and explore microbiome\u2010based interventions.<\/jats:p>\n <\/jats:sec>\n \n Highlights<\/jats:title>\n \n \n \n Examined gut microbiota, inflammation, and metabolic changes in cognitive impairment stages<\/jats:p>\n <\/jats:list-item>\n \n Early metabolic changes in feces detected before plasma alterations<\/jats:p>\n <\/jats:list-item>\n \n Observed shifts in gut microbiota and inflammation associated with cognitive decline<\/jats:p>\n <\/jats:list-item>\n \n Suggests potential for early biomarkers based on gut metabolites<\/jats:p>\n <\/jats:list-item>\n \n Calls for larger, longitudinal studies to validate findings<\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/alz.70844","type":"journal-article","created":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T08:54:36Z","timestamp":1761814476000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Plasma and feces multiomics unveil cognition\u2010associated perturbations of chronic inflammatory pathways of the gut\u2010microbiota\u2013brain axis"],"prefix":"10.1002","volume":"21","author":[{"given":"Farideh","family":"Hosseinkhani","sequence":"first","affiliation":[{"name":"Leiden Academic Centre for Drug Research Leiden University Leiden Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire","family":"Chevalier","sequence":"additional","affiliation":[{"name":"Laboratory of Neuroimaging of Aging (LANVIE) University of Geneva Geneva Switzerland"},{"name":"Geneva Memory Center, Department of Rehabilitation and Geriatrics Geneva University Hospitals Geneva Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moira","family":"Marizzoni","sequence":"additional","affiliation":[{"name":"Laboratory of Biological Psychiatry IRCCS Istituto Centro San Giovanni Di Dio Fatebenefratelli Brescia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rahel","family":"Park","sequence":"additional","affiliation":[{"name":"Laboratory of Neuroimaging of Aging (LANVIE) University of Geneva Geneva Switzerland"},{"name":"Geneva Memory Center, Department of Rehabilitation and Geriatrics Geneva University Hospitals Geneva Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabine","family":"Bos","sequence":"additional","affiliation":[{"name":"Leiden Academic Centre for Drug Research Leiden University Leiden Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alida Kindt","family":"Dunjko","sequence":"additional","affiliation":[{"name":"Leiden Academic Centre for Drug Research Leiden University Leiden Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cornelia M.","family":"van Duijn","sequence":"additional","affiliation":[{"name":"Department of Epidemiology Erasmus University Medical Center Rotterdam Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2931-4295","authenticated-orcid":false,"given":"Amy C.","family":"Harms","sequence":"additional","affiliation":[{"name":"Leiden Academic Centre for Drug Research Leiden University Leiden Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni B.","family":"Frisoni","sequence":"additional","affiliation":[{"name":"Laboratory of Neuroimaging of Aging (LANVIE) University of Geneva Geneva Switzerland"},{"name":"Geneva Memory Center, Department of Rehabilitation and Geriatrics Geneva University Hospitals Geneva Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Hankemeier","sequence":"additional","affiliation":[{"name":"Leiden Academic Centre for Drug Research Leiden University Leiden Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,10,30]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43587-023-00404-2"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41531\u2010021\u201000213\u20107"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392\u2010022\u201000974\u20104"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010017\u201013601\u2010y"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-210259"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201900071R"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.add1236"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-200306"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2018.07.217"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.067272"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2020.100138"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu13062099"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-83428-1"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.045436"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474\u20104422(19)30368\u20100"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2011.03.008"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2011.03.005"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gks808"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41587\u2010019\u20100209\u20109"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3869"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40168-018-0470-z"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/oby.23282"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.3390\/metabo12020165"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.3390\/metabo11060364"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0061217"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0285346"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1904099116"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2024.1478557"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1128\/spectrum.03090-24"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1177\/13872877251337773"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.067334"},{"key":"e_1_2_9_33_1","first-page":"170","article-title":"Raised serum proinflammatory cytokines in Alzheimer's disease with depression","volume":"5","author":"Khemka VK","year":"2014","journal-title":"Aging Dis"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2016.08.019"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-018-0451-2"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.3390\/microorganisms11071825"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2022.136921"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.3945\/an.116.012187"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clnu.2021.02.035"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1111\/imm.13378"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.3390\/life11090934"}],"container-title":["Alzheimer's & Dementia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/alz.70844","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T12:34:04Z","timestamp":1764160444000},"score":1,"resource":{"primary":{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/10.1002\/alz.70844"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10]]},"references-count":40,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2025,10]]}},"alternative-id":["10.1002\/alz.70844"],"URL":"https:\/\/doi.org\/10.1002\/alz.70844","archive":["Portico"],"relation":{},"ISSN":["1552-5260","1552-5279"],"issn-type":[{"value":"1552-5260","type":"print"},{"value":"1552-5279","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10]]},"assertion":[{"value":"2025-06-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-30","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-30","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70844"}}