{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T05:34:52Z","timestamp":1793684092711,"version":"4.5.1"},"reference-count":102,"publisher":"Cambridge University Press (CUP)","license":[{"start":{"date-parts":[[2025,7,7]],"date-time":"2025-07-07T00:00:00Z","timestamp":1751846400000},"content-version":"unspecified","delay-in-days":187,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82471952"],"award-info":[{"award-number":["82471952"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82371928"],"award-info":[{"award-number":["82371928"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["cambridge.org"],"crossmark-restriction":true},"short-container-title":["Psychol. Med."],"published-print":{"date-parts":[[2025]]},"abstract":"<jats:title>Abstract<\/jats:title>\n\t  <jats:sec id=\"S003329172510072X_sec1\">\n\t    <jats:title>Background<\/jats:title>\n\t    <jats:p>Compelling evidence claims that gut microbial dysbiosis may be causally associated with major depressive disorder (MDD), with a particular focus on <jats:italic>Alistipes.<\/jats:italic> However, little is known about the potential microbiota\u2013gut\u2013brain axis mechanisms by which <jats:italic>Alistipes<\/jats:italic> exerts its pathogenic effects in MDD.<\/jats:p>\n\t  <\/jats:sec>\n\t  <jats:sec id=\"S003329172510072X_sec2\" sec-type=\"methods\">\n\t    <jats:title>Methods<\/jats:title>\n\t    <jats:p>We collected data from 16S rDNA amplicon sequencing, untargeted metabolomics, and multimodal brain magnetic resonance imaging from 111 MDD patients and 102 healthy controls. We used multistage linked analyses, including group comparisons, correlation analyses, and mediation analyses, to explore the relationships between the gut microbiome (<jats:italic>Alistipes<\/jats:italic>), fecal metabolome, brain imaging, and behaviors in MDD.<\/jats:p>\n\t  <\/jats:sec>\n\t  <jats:sec id=\"S003329172510072X_sec3\" sec-type=\"results\">\n\t    <jats:title>Results<\/jats:title>\n\t    <jats:p>Gut microbiome analysis demonstrated that MDD patients had a higher abundance of <jats:italic>Alistipes<\/jats:italic> relative to controls. Partial least squares regression revealed that the increased <jats:italic>Alistipes<\/jats:italic> was significantly associated with fecal metabolome in MDD, involving a range of metabolites mainly enriched for amino acid, vitamin B, and bile acid metabolism pathways. Correlation analyses showed that the <jats:italic>Alistipes<\/jats:italic>-related metabolites were associated with a wide array of brain imaging measures involving gray matter morphology, spontaneous brain function, and white matter integrity, among which the brain functional measures were, in turn, associated with affective symptoms (anxiety and anhedonia) and cognition (sustained attention) in MDD. Of more importance, further mediation analyses identified multiple significant mediation pathways where the brain functional measures in the visual cortex mediated the associations of metabolites with behavioral deficits.<\/jats:p>\n\t  <\/jats:sec>\n\t  <jats:sec id=\"S003329172510072X_sec4\" sec-type=\"conclusions\">\n\t    <jats:title>Conclusion<\/jats:title>\n\t    <jats:p>Our findings provide a proof of concept that <jats:italic>Alistipes<\/jats:italic> and its related metabolites play a critical role in the pathophysiology of MDD through the microbiota\u2013gut\u2013brain axis.<\/jats:p>\n\t  <\/jats:sec>","DOI":"10.1017\/s003329172510072x","type":"journal-article","created":{"date-parts":[[2025,7,7]],"date-time":"2025-07-07T09:38:03Z","timestamp":1751881083000},"update-policy":"https:\/\/doi.org\/10.1017\/policypage","source":"Crossref","is-referenced-by-count":31,"title":["Multi-omics analyses of the gut microbiome, fecal metabolome, and multimodal brain MRI reveal the role of <i>Alistipes<\/i> and its related metabolites in major depressive disorder"],"prefix":"10.1017","volume":"55","author":[{"given":"Siyu","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifei","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhonghao","family":"Rao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongqi","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Kong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shukun","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dao-min","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongqiang","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiajia","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"56","published-online":{"date-parts":[[2025,7,7]]},"reference":[{"key":"S003329172510072X_r88","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2003.12.030"},{"key":"S003329172510072X_r100","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-018-0135-7"},{"key":"S003329172510072X_r40","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2022.106145"},{"key":"S003329172510072X_r47","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)31948-2"},{"key":"S003329172510072X_r42","doi-asserted-by":"publisher","DOI":"10.1016\/j.pnpbp.2024.111151"},{"key":"S003329172510072X_r53","doi-asserted-by":"publisher","DOI":"10.1111\/nmo.12378"},{"key":"S003329172510072X_r29","doi-asserted-by":"publisher","DOI":"10.1111\/j.2044-8341.1959.tb00467.x"},{"key":"S003329172510072X_r9","doi-asserted-by":"publisher","DOI":"10.1038\/s41398-021-01755-3"},{"key":"S003329172510072X_r18","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2023.120415"},{"key":"S003329172510072X_r7","doi-asserted-by":"publisher","DOI":"10.1017\/S0033291722000897"},{"key":"S003329172510072X_r23","doi-asserted-by":"publisher","DOI":"10.1016\/j.jad.2023.01.051"},{"key":"S003329172510072X_r55","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.00906"},{"key":"S003329172510072X_r61","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2011.06.072"},{"key":"S003329172510072X_r62","doi-asserted-by":"publisher","DOI":"10.1099\/ijsem.0.000617"},{"key":"S003329172510072X_r22","doi-asserted-by":"publisher","DOI":"10.3390\/nu14132661"},{"key":"S003329172510072X_r82","doi-asserted-by":"publisher","DOI":"10.1007\/s12021-016-9299-4"},{"key":"S003329172510072X_r68","doi-asserted-by":"publisher","DOI":"10.1111\/pcn.13368"},{"key":"S003329172510072X_r66","doi-asserted-by":"publisher","DOI":"10.1099\/ijs.0.64318-0"},{"key":"S003329172510072X_r50","doi-asserted-by":"publisher","DOI":"10.1016\/S0176-6724(86)80058-X"},{"key":"S003329172510072X_r21","doi-asserted-by":"publisher","DOI":"10.1080\/10408398.2013.876960"},{"key":"S003329172510072X_r13","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2024.07.021"},{"key":"S003329172510072X_r77","doi-asserted-by":"publisher","DOI":"10.1590\/1516-4446-2012-1048"},{"key":"S003329172510072X_r80","doi-asserted-by":"publisher","DOI":"10.1007\/s12264-023-01052-7"},{"key":"S003329172510072X_r24","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-022-01806-1"},{"key":"S003329172510072X_r84","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2020.00050"},{"key":"S003329172510072X_r78","doi-asserted-by":"publisher","DOI":"10.1021\/ac051312t"},{"key":"S003329172510072X_r17","doi-asserted-by":"publisher","DOI":"10.1038\/nrn3346"},{"key":"S003329172510072X_r46","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2023.06.009"},{"key":"S003329172510072X_r70","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1001414107"},{"key":"S003329172510072X_r72","first-page":"294","article-title":"Metabolomics for the masses: The future of metabolomics in a personalized world","volume":"3","author":"Trivedi","year":"2017","journal-title":"New Horizons in Translational Medicine"},{"key":"S003329172510072X_r87","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-023-01519-z"},{"key":"S003329172510072X_r28","doi-asserted-by":"publisher","DOI":"10.2466\/pms.2003.97.3f.1209"},{"key":"S003329172510072X_r48","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-023-00454-1"},{"key":"S003329172510072X_r93","doi-asserted-by":"publisher","DOI":"10.21037\/qims-20-970"},{"key":"S003329172510072X_r51","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2016.11.052"},{"key":"S003329172510072X_r98","doi-asserted-by":"publisher","DOI":"10.1016\/j.pnpbp.2021.110468"},{"key":"S003329172510072X_r5","doi-asserted-by":"publisher","DOI":"10.1021\/ac051495j"},{"key":"S003329172510072X_r12","doi-asserted-by":"publisher","DOI":"10.1038\/tp.2016.209"},{"key":"S003329172510072X_r49","doi-asserted-by":"publisher","DOI":"10.1093\/schbul\/sbae020"},{"key":"S003329172510072X_r52","doi-asserted-by":"publisher","DOI":"10.1038\/nrd.2017.16"},{"key":"S003329172510072X_r90","doi-asserted-by":"publisher","DOI":"10.1039\/b914751a"},{"key":"S003329172510072X_r36","doi-asserted-by":"publisher","DOI":"10.1017\/S0033291721000441"},{"key":"S003329172510072X_r76","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2016.05.005"},{"key":"S003329172510072X_r73","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3393"},{"key":"S003329172510072X_r59","doi-asserted-by":"publisher","DOI":"10.1038\/nrd2462"},{"key":"S003329172510072X_r25","doi-asserted-by":"publisher","DOI":"10.1021\/acs.analchem.1c00816"},{"key":"S003329172510072X_r16","doi-asserted-by":"publisher","DOI":"10.1016\/0165-1781(88)90076-5"},{"key":"S003329172510072X_r60","doi-asserted-by":"publisher","DOI":"10.1016\/j.jad.2020.01.102"},{"key":"S003329172510072X_r75","doi-asserted-by":"publisher","DOI":"10.1016\/j.mam.2017.03.003"},{"key":"S003329172510072X_r81","doi-asserted-by":"publisher","DOI":"10.1016\/j.ynstr.2022.100479"},{"key":"S003329172510072X_r99","doi-asserted-by":"publisher","DOI":"10.1093\/schbul\/sbx051"},{"key":"S003329172510072X_r14","first-page":"585","article-title":"A clinician\u2019s guide to microbiome analysis","volume":"14","author":"Claesson","year":"2017","journal-title":"Nature Reviews: Gastroenterology and Hepatology"},{"key":"S003329172510072X_r91","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2024.01.003"},{"key":"S003329172510072X_r30","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.23.1.56"},{"key":"S003329172510072X_r15","doi-asserted-by":"publisher","DOI":"10.1101\/mcs.a000588"},{"key":"S003329172510072X_r63","doi-asserted-by":"publisher","DOI":"10.3390\/nu10121939"},{"key":"S003329172510072X_r71","first-page":"681","article-title":"Mediation analysis in medical research","volume":"120","author":"T\u00f6nnies","year":"2023","journal-title":"Deutsches Arzteblatt international"},{"key":"S003329172510072X_r57","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(06)70598-1"},{"key":"S003329172510072X_r41","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2023.104527"},{"key":"S003329172510072X_r69","doi-asserted-by":"publisher","DOI":"10.1017\/S0033291722003750"},{"key":"S003329172510072X_r74","doi-asserted-by":"publisher","DOI":"10.1113\/JP276431"},{"key":"S003329172510072X_r27","first-page":"630","article-title":"Metabolomics as a tool for cardiac research","volume":"8","author":"Griffin","year":"2011","journal-title":"Nature Reviews: Cardiology"},{"key":"S003329172510072X_r8","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-024-02538-0"},{"key":"S003329172510072X_r58","doi-asserted-by":"publisher","DOI":"10.1186\/s12874-021-01426-3"},{"key":"S003329172510072X_r86","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2011.02.007"},{"key":"S003329172510072X_r94","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2016.44"},{"key":"S003329172510072X_r31","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awac041"},{"key":"S003329172510072X_r26","doi-asserted-by":"publisher","DOI":"10.3390\/ijms231911245"},{"key":"S003329172510072X_r39","doi-asserted-by":"publisher","DOI":"10.1016\/j.nicl.2017.01.004"},{"key":"S003329172510072X_r65","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2015.266"},{"key":"S003329172510072X_r95","doi-asserted-by":"publisher","DOI":"10.1016\/j.jad.2020.01.096"},{"key":"S003329172510072X_r83","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aba8555"},{"key":"S003329172510072X_r64","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2006.02.024"},{"key":"S003329172510072X_r85","doi-asserted-by":"publisher","DOI":"10.1002\/hbm.21095"},{"key":"S003329172510072X_r44","doi-asserted-by":"publisher","DOI":"10.1109\/42.746714"},{"key":"S003329172510072X_r33","doi-asserted-by":"publisher","DOI":"10.1016\/j.psychres.2018.03.070"},{"key":"S003329172510072X_r37","doi-asserted-by":"publisher","DOI":"10.3390\/nu8020068"},{"key":"S003329172510072X_r2","doi-asserted-by":"publisher","DOI":"10.1006\/nimg.2000.0582"},{"key":"S003329172510072X_r56","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.03473-15"},{"key":"S003329172510072X_r45","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-022-01540-8"},{"key":"S003329172510072X_r1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2007.07.007"},{"key":"S003329172510072X_r4","doi-asserted-by":"publisher","DOI":"10.1016\/j.aca.2013.01.015"},{"key":"S003329172510072X_r67","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2024.120918"},{"key":"S003329172510072X_r89","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.braindev.2006.07.002","article-title":"Altered baseline brain activity in children with ADHD revealed by resting-state functional MRI","volume":"29","author":"Zhang","year":"2007","journal-title":"Brain and Development"},{"key":"S003329172510072X_r101","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneumeth.2008.04.012"},{"key":"S003329172510072X_r6","doi-asserted-by":"publisher","DOI":"10.1080\/1028415X.2022.2031494"},{"key":"S003329172510072X_r34","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2015.03.016"},{"key":"S003329172510072X_r35","doi-asserted-by":"publisher","DOI":"10.1503\/jpn.150341"},{"key":"S003329172510072X_r32","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24032231"},{"key":"S003329172510072X_r92","doi-asserted-by":"publisher","DOI":"10.1186\/s12888-024-05942-6"},{"key":"S003329172510072X_r102","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2612-10.2010"},{"key":"S003329172510072X_r20","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-021-00368-1"},{"key":"S003329172510072X_r79","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23010305"},{"key":"S003329172510072X_r11","doi-asserted-by":"publisher","DOI":"10.1016\/j.jad.2022.03.079"},{"key":"S003329172510072X_r10","doi-asserted-by":"publisher","DOI":"10.15698\/mic2019.10.693"},{"key":"S003329172510072X_r3","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2005.02.018"},{"key":"S003329172510072X_r54","doi-asserted-by":"publisher","DOI":"10.1016\/S0924-977X(03)00099-3"},{"key":"S003329172510072X_r96","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyg.2019.02130"},{"key":"S003329172510072X_r38","doi-asserted-by":"publisher","DOI":"10.1159\/000152378"},{"key":"S003329172510072X_r19","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2012.09.050"},{"key":"S003329172510072X_r43","doi-asserted-by":"publisher","DOI":"10.1007\/s13238-020-00724-8"},{"key":"S003329172510072X_r97","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-024-06665-w"}],"container-title":["Psychological Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.cambridge.org\/core\/services\/aop-cambridge-core\/content\/view\/S003329172510072X","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,7]],"date-time":"2025-07-07T09:38:04Z","timestamp":1751881084000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.cambridge.org\/core\/product\/identifier\/S003329172510072X\/type\/journal_article"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025]]},"references-count":102,"alternative-id":["S003329172510072X"],"URL":"https:\/\/doi.org\/10.1017\/s003329172510072x","relation":{},"ISSN":["0033-2917","1469-8978"],"issn-type":[{"value":"0033-2917","type":"print"},{"value":"1469-8978","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025]]},"assertion":[{"value":"\u00a9 The Author(s), 2025. Published by Cambridge University Press","name":"copyright","label":"Copyright","group":{"name":"copyright_and_licensing","label":"Copyright and Licensing"}},{"value":"This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http:\/\/creativecommons.org\/licenses\/by\/4.0), which permits unrestricted re-use, distribution and reproduction, provided the original article is properly cited.","name":"license","label":"License","group":{"name":"copyright_and_licensing","label":"Copyright and Licensing"}},{"value":"This content has been made available to all.","name":"free","label":"Free to read"}],"article-number":"e190"}}