{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T10:03:10Z","timestamp":1789380190399,"version":"build-2803163510"},"reference-count":69,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T00:00:00Z","timestamp":1783468800000},"content-version":"vor","delay-in-days":7,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Health Science Reports"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Aims<\/jats:title>\n                    <jats:p>The \u201coral\u2013microbiota\u2013brain axis\u201d has been hypothesized to contribute to Alzheimer's disease (AD) pathogenesis, but causal evidence remains limited. We performed a bidirectional Mendelian randomization (MR) study to investigate potential genetic causality between oral microbiota and AD in East Asians.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Two\u2010sample MR integrated genome\u2010wide data from 2984 Chinese participants (saliva\/tongue dorsum microbiomes) and 7036 Japanese participants (3962 AD cases\/4074 controls). Genetic instruments were selected using pragmatically moderated significance thresholds (forward:\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20095\u2009\u00d7\u200910\n                      <jats:sup>\u22124<\/jats:sup>\n                      ; reverse:\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20095\u2009\u00d7\u200910\n                      <jats:sup>\u22125<\/jats:sup>\n                      ), with causality assessed via inverse\u2010variance weighted (IVW) regression and four Supporting methods. Sensitivity analyses validated robustness. We examined 3117 microbial taxa\u2010AD pairs, followed by exploratory Gene Ontology (GO) enrichment analysis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Forward MR identified 12 candidate causal taxa: five with risk\u2010increasing associations (e.g.,\n                      <jats:italic>Prevotella<\/jats:italic>\n                      sp. MGS2526, OR\u2009=\u20091.32 [1.14\u20131.52],\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20091.4\u2009\u00d7\u200910\n                      <jats:sup>\u22124<\/jats:sup>\n                      ) and seven with protective associations (e.g.,\n                      <jats:italic>Streptococcus mitis<\/jats:italic>\n                      MGS519, OR\u2009=\u20090.81 [0.69\u20130.94],\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20097.9\u2009\u00d7\u200910\n                      <jats:sup>\u22123<\/jats:sup>\n                      ). Reverse MR suggested AD may influence the abundance of three microbial species (e.g.,\n                      <jats:italic>Streptococcus sanguinis<\/jats:italic>\n                      MGS515, OR\u2009=\u20091.04 [1.01\u20131.07],\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20093.6\u2009\u00d7\u200910\n                      <jats:sup>\u22123<\/jats:sup>\n                      ). Exploratory GO analysis highlighted enrichment in pathways related to synaptic transmission and nutrient metabolism.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study provides genetic evidence consistent with a bidirectional relationship between oral microbiota and AD in East Asians, nominating 15 microbial taxa as candidates for further investigation. The implicated biological pathways offer hypotheses for mechanistic links via the oral\u2013microbiota\u2013brain axis. These findings advance the etiological understanding of AD and highlight priority targets for future experimental and clinical validation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/hsr2.72632","type":"journal-article","created":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T04:03:28Z","timestamp":1783569808000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Oral Microbiota and Alzheimer's Disease: A Bidirectional Mendelian Randomization Study Based on East Asian Ethnicity"],"prefix":"10.1002","volume":"9","author":[{"given":"Jieyi","family":"Li","sequence":"first","affiliation":[{"name":"Department of Stomatology University\u2010Town Hospital of Chongqing Medical University Chongqing P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingqing","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Stomatology University\u2010Town Hospital of Chongqing Medical University Chongqing P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Qin","sequence":"additional","affiliation":[{"name":"Department of Stomatology University\u2010Town Hospital of Chongqing Medical University Chongqing P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-2513-8968","authenticated-orcid":false,"given":"Honglei","family":"Xue","sequence":"additional","affiliation":[{"name":"Department of Stomatology University\u2010Town Hospital of Chongqing Medical University Chongqing P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,8]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2468-2667(21)00249-8"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(24)00038-3"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.2174\/1570159X18666200528142429"},{"key":"e_1_2_13_5_1","doi-asserted-by":"crossref","unstructured":"2024 Alzheimer's Disease Facts and Figures \u201dAlzheimer's & Dementia: The Journal of the Alzheimer's Association20 no.5(2024):3708\u20133821.","DOI":"10.1002\/alz.13809"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vhri.2023.09.008"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-019-0333-5"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.5114\/fn.2019.85929"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms232213954"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.oooo.2012.03.028"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.2174\/156720510791162359"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00784-017-2264-2"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aau3333"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2020.25515"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-200064"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2017.00327"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.60.2.194"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-220760"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1080\/19490976.2020.1848158"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-215520"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/odi.14110"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-023-02216-7"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.2174\/1566524023666220819140748"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/febs.15571"},{"key":"e_1_2_13_25_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2021.633735"},{"key":"e_1_2_13_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/odi.14054"},{"key":"e_1_2_13_27_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-022-00522-2"},{"key":"e_1_2_13_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/prd.12429"},{"key":"e_1_2_13_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2017.06.005"},{"key":"e_1_2_13_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.3034"},{"key":"e_1_2_13_31_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2017.17219"},{"key":"e_1_2_13_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41421-021-00356-0"},{"key":"e_1_2_13_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41398-021-01272-3"},{"key":"e_1_2_13_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/gepi.21758"},{"key":"e_1_2_13_35_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkad347"},{"key":"e_1_2_13_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-09234-6"},{"issue":"1","key":"e_1_2_13_37_1","first-page":"S45","article-title":"Porphyromonas gingivalis and Alzheimer Disease: Recent Findings and Potential Therapies","volume":"91","author":"Ryder M. I.","year":"2020","journal-title":"Journal of Periodontology"},{"key":"e_1_2_13_38_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-025-01941-1"},{"key":"e_1_2_13_39_1","doi-asserted-by":"publisher","DOI":"10.1099\/00221287-148-5-1379"},{"key":"e_1_2_13_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.annepidem.2019.03.006"},{"key":"e_1_2_13_41_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0765.2011.01409.x"},{"key":"e_1_2_13_42_1","doi-asserted-by":"publisher","DOI":"10.1111\/imm.12760"},{"key":"e_1_2_13_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-019-0405-7"},{"key":"e_1_2_13_44_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2314337121"},{"key":"e_1_2_13_45_1","doi-asserted-by":"publisher","DOI":"10.31083\/j.jin2102073"},{"key":"e_1_2_13_46_1","doi-asserted-by":"publisher","DOI":"10.1128\/spectrum.00998-22"},{"key":"e_1_2_13_47_1","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.13.4.547"},{"key":"e_1_2_13_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2023.01.013"},{"key":"e_1_2_13_49_1","doi-asserted-by":"publisher","DOI":"10.1264\/jsme2.ME14054"},{"key":"e_1_2_13_50_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu15204365"},{"key":"e_1_2_13_51_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aau8317"},{"key":"e_1_2_13_52_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-024-05813-4"},{"key":"e_1_2_13_53_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20201915"},{"key":"e_1_2_13_54_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.01158"},{"key":"e_1_2_13_55_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.14141"},{"key":"e_1_2_13_56_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-05753-x"},{"key":"e_1_2_13_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2015.12.012"},{"key":"e_1_2_13_58_1","doi-asserted-by":"publisher","DOI":"10.1080\/17460913.2024.2423524"},{"key":"e_1_2_13_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2024.106484"},{"key":"e_1_2_13_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.meegid.2021.104877"},{"key":"e_1_2_13_61_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-190587"},{"key":"e_1_2_13_62_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2024.1370736"},{"key":"e_1_2_13_63_1","doi-asserted-by":"publisher","DOI":"10.3390\/pathogens8020059"},{"key":"e_1_2_13_64_1","doi-asserted-by":"publisher","DOI":"10.1080\/20002297.2020.1851112"},{"key":"e_1_2_13_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joen.2024.08.014"},{"key":"e_1_2_13_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.micpath.2024.106881"},{"key":"e_1_2_13_67_1","doi-asserted-by":"publisher","DOI":"10.1080\/1040841X.2022.2163613"},{"key":"e_1_2_13_68_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2023.1269843"},{"key":"e_1_2_13_69_1","doi-asserted-by":"publisher","DOI":"10.2174\/156652313804806615"},{"key":"e_1_2_13_70_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2023.156232"}],"container-title":["Health Science Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/hsr2.72632","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/hsr2.72632","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/hsr2.72632","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T09:11:47Z","timestamp":1789377107000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/hsr2.72632"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7]]},"references-count":69,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2026,7]]}},"alternative-id":["10.1002\/hsr2.72632"],"URL":"https:\/\/doi.org\/10.1002\/hsr2.72632","archive":["Portico"],"relation":{},"ISSN":["2398-8835","2398-8835"],"issn-type":[{"value":"2398-8835","type":"print"},{"value":"2398-8835","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7]]},"assertion":[{"value":"2025-05-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-01","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-08","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e72632"}}