{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T23:57:09Z","timestamp":1789516629848,"version":"build-2803163510"},"reference-count":86,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T00:00:00Z","timestamp":1780444800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100014188","name":"Ministry of Science and ICT, South Korea","doi-asserted-by":"publisher","award":["RS-2022-NR071880"],"award-info":[{"award-number":["RS-2022-NR071880"]}],"id":[{"id":"10.13039\/501100014188","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003052","name":"Ministry of Trade, Industry and Energy","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003052","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003625","name":"Ministry of Health and Welfare","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003625","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003566","name":"Ministry of Oceans and Fisheries","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003566","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002496","name":"Hongik University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002496","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    The gut-liver axis maintains metabolic homeostasis and immune regulation through continuous bidirectional communication, and its dysregulation contributes to a range of metabolic, inflammatory, and immune-mediated diseases. Integrated gut-liver axis model systems offer unique tools for dissecting these complex interactions by isolating individual variables that are difficult to disentangle\n                    <jats:italic>in vivo<\/jats:italic>\n                    , while allowing flexible experimental controls over them. Here, we review advances in gut-liver axis models from static co-cultures to microfluidic systems and their applications in pharmacokinetic and mechanistic studies. We identify underexplored areas, including metabolite-mediated gut-liver crosstalk, immune-mediated interorgan communication, and disease-specific modeling, and outline technical challenges to achieving physiologically faithful and reliable integrated platforms. By addressing these challenges, gut-liver axis models will contribute to a mechanistic understanding of gut-liver pathobiology that is difficult to achieve through clinical studies, animal models, or individual organ systems alone.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1858289","type":"journal-article","created":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T09:12:08Z","timestamp":1780477928000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["In vitro models of the gut-liver axis: what we\u2019ve learned and what remains to be built"],"prefix":"10.3389","volume":"17","author":[{"given":"Jong Hwan","family":"Sung","sequence":"first","affiliation":[{"name":"Department of Chemical Engineering, Hongik University","place":["Seoul, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raehyun","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biological and Chemical Engineering, Hongik University","place":["Sejong, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2022.09.017","article-title":"Gut-liver axis: Pathophysiological concepts and clinical implications","volume":"34","author":"Tilg","year":"2022","journal-title":"Cell Metab"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jnutbio.2014.02.013","article-title":"Proposing a Caco-2\/HepG2 cell model for in vitro iron absorption studies","volume":"25","author":"Scheers","year":"2014","journal-title":"J Nutr Biochem"},{"key":"B3","doi-asserted-by":"publisher","first-page":"437","DOI":"10.3390\/nu8070437","article-title":"Hypocholesterolaemic activity of lupin peptides: Investigation on the crosstalk between human enterocytes and hepatocytes using a co-culture system including Caco-2 and 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