{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T10:21:47Z","timestamp":1793701307248,"version":"4.5.1"},"reference-count":49,"publisher":"American Society for Clinical Investigation","issue":"8","license":[{"start":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T00:00:00Z","timestamp":1776816000000},"content-version":"vor","delay-in-days":43,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000052","name":"NIH Office of the Director","doi-asserted-by":"crossref","award":["R01DK085252,R01DK138591"],"award-info":[{"award-number":["R01DK085252,R01DK138591"]}],"id":[{"id":"10.13039\/100000052","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100001424","name":"American Liver Foundation","doi-asserted-by":"crossref","award":["Liver Scholar Award"],"award-info":[{"award-number":["Liver Scholar Award"]}],"id":[{"id":"10.13039\/100001424","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100013015","name":"Cedars-Sinai Medical Center","doi-asserted-by":"crossref","award":["Clinical Scholar Award"],"award-info":[{"award-number":["Clinical Scholar Award"]}],"id":[{"id":"10.13039\/100013015","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100013015","name":"Cedars-Sinai Medical Center","doi-asserted-by":"crossref","award":["Cedars-Sinai Cancer Community Outreach"],"award-info":[{"award-number":["Cedars-Sinai Cancer Community Outreach"]}],"id":[{"id":"10.13039\/100013015","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100013015","name":"Cedars-Sinai Medical Center","doi-asserted-by":"crossref","award":["Engagement Development Fund"],"award-info":[{"award-number":["Engagement Development Fund"]}],"id":[{"id":"10.13039\/100013015","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,4,22]]},"abstract":"<jats:p>\n                    Metabolic dysfunction\u2013associated steatotic liver disease (MASLD) is a global health concern with limited interventions. While the role of gut bacteria in MASLD has been extensively studied, the contribution of gut fungi remains largely unexplored. This study investigates the impact of fungal dysbiosis and the role of CARD9, a key adaptor protein in fungal sensing on gut-liver axis dysfunction in MASLD. Patients with advanced liver fibrosis exhibited distinct mycobiota profiles. Using a\n                    <jats:italic>Card9<\/jats:italic>\n                    -deficient mouse model subjected to high-fat, high-glucose\/-fructose feeding, we observed exacerbated liver injury and fibrosis accompanied by fungal dysbiosis, paralleling our findings in human patients. Beyond its established expression in myeloid cells,\n                    <jats:italic>CARD9<\/jats:italic>\n                    was also detected in intestinal enterocytes where its expression was diminished under metabolic stress. Intestinal organoids with CARD9 inhibition had reduced expression of antimicrobial Reg3g, the tight junction protein ZO-1, and the antifungal enteroendocrine hormone PYY. These findings suggest that CARD9 maintains gut barrier integrity, preventing microbial translocation and subsequent liver injury and fibrosis. Our results provide insights into the interplay between fungal dysbiosis, gut barrier dysfunction, and MASLD, and identify CARD9 as a key protein within this axis.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.190690","type":"journal-article","created":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T16:00:53Z","timestamp":1773158453000},"source":"Crossref","is-referenced-by-count":1,"title":["Loss of fungal sensing exacerbates liver injury in a murine model of MASLD"],"prefix":"10.1172","volume":"11","author":[{"given":"Vijay","family":"Pandyarajan","sequence":"first","affiliation":[{"name":"Karsh Division of Gastroenterology and Hepatology, Department of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"So Yeon","family":"Kim","sequence":"additional","affiliation":[{"name":"Karsh Division of Gastroenterology and Hepatology, Department of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Tsuchiya","sequence":"additional","affiliation":[{"name":"Karsh Division of Gastroenterology and Hepatology, Department of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Selena","family":"Liu","sequence":"additional","affiliation":[{"name":"Karsh Division of Gastroenterology and Hepatology, Department of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sadam H.","family":"Bhat","sequence":"additional","affiliation":[{"name":"Karsh Division of Gastroenterology and Hepatology, Department of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jieun","family":"Kim","sequence":"additional","affiliation":[{"name":"Karsh Division of Gastroenterology and Hepatology, Department of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2989-658X","authenticated-orcid":true,"given":"David M.","family":"Underhill","sequence":"additional","affiliation":[{"name":"Karsh Division of Gastroenterology and Hepatology, Department of Medicine, and"},{"name":"Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mazen","family":"Noureddin","sequence":"additional","affiliation":[{"name":"Karsh Division of Gastroenterology and Hepatology, Department of Medicine, and"},{"name":"Houston Methodist Hospital, Houston, Texas, USA."},{"name":"Houston Research Institute, Houston, Texas, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shelly C.","family":"Lu","sequence":"additional","affiliation":[{"name":"Karsh Division of Gastroenterology and Hepatology, Department of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9472-6085","authenticated-orcid":true,"given":"Ekihiro","family":"Seki","sequence":"additional","affiliation":[{"name":"Karsh Division of Gastroenterology and Hepatology, Department of Medicine, and"},{"name":"Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2026,3,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1097\/HEP.0000000000000004"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/S2468-1253(22)00165-0"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.jceh.2022.12.005"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2036.2007.03426.x"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2014.12.012"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3390\/ijms17050774"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1097\/MOG.0000000000000139"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2016.08.024"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-00900-1"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1038\/nature05414"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2008.02.015"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1128\/mSystems.00201-17"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1111\/liv.15160"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-019-0186-y"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1172\/JCI90562"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2021.11.029"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1002\/oby.23073"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12901"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2231"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.01836"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4102"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1002\/hep.24726"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2016.02.014"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0810719"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0080169"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-18928-1"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1177\/0300060520978122"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.add8945"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20221437"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1443.024"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2020868118"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R114.635995"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01210-20"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1128\/aem.37.3.365-368.1979"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2018.01655"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1080\/07391102.2023.2273435"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.mi.46.100192.002333"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.89890"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro1245"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1126\/science.abq3178"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.4254\/wjh.v6.i5.274"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1002\/cpbi.100"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.03006-05"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.12688\/f1000research.15704.1"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.3390\/microorganisms8121910"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0061217"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.21105\/joss.03201"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2019"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1038\/s41596-021-00607-0"}],"container-title":["JCI Insight"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/insight.jci.org\/articles\/view\/190690\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T19:14:18Z","timestamp":1778872458000},"score":1,"resource":{"primary":{"URL":"https:\/\/insight.jci.org\/articles\/view\/190690"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,10]]},"references-count":49,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,2,26]]},"published-print":{"date-parts":[[2026,4,22]]}},"alternative-id":["10.1172\/jci.insight.190690"],"URL":"https:\/\/doi.org\/10.1172\/jci.insight.190690","relation":{},"ISSN":["2379-3708"],"issn-type":[{"value":"2379-3708","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,10]]},"article-number":"e190690"}}