{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T03:21:17Z","timestamp":1788146477114,"version":"build-2803163510"},"reference-count":61,"publisher":"SAGE Publications","issue":"2","license":[{"start":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T00:00:00Z","timestamp":1764720000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Several recent studies have confirmed a causal relationship between gut microbiota and Alzheimer's disease (AD), but the potential mediators remain unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This study aimed first to investigate the causal relationship between gut microbiota and AD, and second to explore potential mediators involved in this relationship.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We used a two-step Mendelian randomization study. Firstly, we mainly used inverse-variance weighted (IVW), weighted median, weighted mode, MR-Egger, and simple mode methods to assess the causal relationship between gut microbiota and AD. Secondly, we conducted mediation analysis to evaluate the roles of inflammatory factors, immune cells, and metabolites in this causal pathway. In addition, we performed sensitivity analysis, Steiger test, and linkage disequilibrium score regression (LDSC).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Our results showed that ten types of gut microbiota were causally associated with AD, of which seven were associated with an increased risk of AD and three with a reduced risk. In addition, the mediation analysis showed that CD45 on Mo MDSC mediated 21.89% of the effect of class Actinobacteria on AD, while the cortisol to taurocholate ratio mediated 18.35% of the effect of genus Lactococcus on AD. Beta-hydroxyisovalerate and glycodeoxycholate levels respectively mediated 10.56% and 16.22% of the effects of class Betaproteobacteria on AD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our research not only supports modulating gut microbiota as a preventive measure for AD but also emphasizes the mediating roles of inflammatory factors, immune cells, and metabolites. These findings enhance our understanding of the gut-brain axis, providing new perspectives and potential targets for AD prevention.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/13872877251401157","type":"journal-article","created":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T12:00:37Z","timestamp":1764763237000},"page":"876-888","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["Mediators between gut microbiota and Alzheimer's disease: A mediation Mendelian randomization study"],"prefix":"10.1177","volume":"109","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-2355-6554","authenticated-orcid":false,"given":"Xin-Yu","family":"Dong","sequence":"first","affiliation":[{"name":"Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Han","sequence":"additional","affiliation":[{"name":"Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-9133-7329","authenticated-orcid":false,"given":"Tian-bin","family":"Wang","sequence":"additional","affiliation":[{"name":"CT room, Heilongjiang Provincial Hospital, Harbin, Heilongjiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-4656-2532","authenticated-orcid":false,"given":"Yu-Bo","family":"Han","sequence":"additional","affiliation":[{"name":"The First Department of Cardiovascular, First Affiliated Hospital, Heilongjiang University of Traditional Chinese Medicine, Harbin, Heilongjiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-6371-8805","authenticated-orcid":false,"given":"Li","family":"Liu","sequence":"additional","affiliation":[{"name":"The First Department of Cardiovascular, First Affiliated Hospital, Heilongjiang University of Traditional Chinese Medicine, Harbin, Heilongjiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,12,3]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/alz.13809"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2468-2667(21)00249-8"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/procel\/pwae026"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2022.114418"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1111\/febs.15571"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.3390\/nu14030668"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.18632\/aging.202994"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.3892\/ijmm.2023.5314"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1515\/mr-2024-0064"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.14283\/jpad.2024.113"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-020-01961-8"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-020-00763-1"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-019-0358-2"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-020-0684-4"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-022-01270-1"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-023-01588-w"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-023-02999-0"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.xops.2024.100684"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1406291"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwt084"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1002\/gepi.21965"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1002\/sim.7221"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1002\/sim.6522"},{"key":"e_1_3_3_25_2","article-title":"Orienting the causal relationship between imprecisely measured traits using GWAS summary data","volume":"13","author":"Hemani G","year":"2017","unstructured":"Hemani G, Tilling K, Davey Smith G. 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