{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T17:04:24Z","timestamp":1790183064241,"version":"4.1.0"},"reference-count":124,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T00:00:00Z","timestamp":1790121600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The gut\u2013liver axis is central to the systemic complications of liver cirrhosis, but it is usually described as a linear cascade in which barrier failure releases microbial products that activate a downstream immune response. This review proposes instead a four-compartment framework, in which the epithelial\/barrier, innate immune, adaptive effector, and stromal\u2013endothelial compartments\u2014the last including the gut\u2013vascular barrier\u2014are treated as reciprocally interacting nodes, and pathological bacterial translocation is treated as both an input to and an output of the network rather than as its endpoint. Applying this framework across the stages of cirrhosis, we examine how tight-junction disassembly, mucus-layer thinning, Paneth-cell dysfunction and reduced secretory IgA, together with dysbiosis and small-intestinal bacterial overgrowth, permit translocation; how translocated bacteria and pathogen-associated molecular patterns activate all four compartments; and how the resulting cytokine circuits further degrade the barrier, generating feed-forward loops that underlie cirrhosis-associated immune dysfunction and chronic systemic inflammation. We relate these circuits to spontaneous bacterial peritonitis, hepatic encephalopathy, aggravated portal hypertension, and acute-on-chronic liver failure, distinguishing throughout between mechanisms demonstrated in humans and those inferred from animal or in vitro models. We identified evidence through structured searches of PubMed\/MEDLINE, Embase, and Web of Science, and report it according to the SANRA checklist. Framed as a network, biomarkers become compartment-specific reporters, and barrier-, microbiome-, and immune-directed therapies become interventions at defined nodes and edges\u2014a view that clarifies both their rationale and the current limits of the evidence.<\/jats:p>","DOI":"10.3390\/cells15191739","type":"journal-article","created":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T16:10:31Z","timestamp":1790179831000},"page":"1739","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cellular Crosstalk at the Gut\u2013Liver Interface in Liver Cirrhosis: Epithelial Barrier Failure, Bacterial Translocation and Immune Activation as a Bidirectional Network"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2556-1317","authenticated-orcid":false,"given":"Thomas N.","family":"Nitsotolis","sequence":"first","affiliation":[{"name":"1st Department of Internal Medicine and Infectious Diseases, Faculty of Medicine, School of Health Sciences, University of Ioannina, University Campus, 45110 Ioannina, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6901-3681","authenticated-orcid":false,"given":"Stelios F.","family":"Assimakopoulos","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Medical School, University of Patras, 26504 Patras, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-3763-4064","authenticated-orcid":false,"given":"Eleftheria","family":"Mastoridou","sequence":"additional","affiliation":[{"name":"1st Department of Internal Medicine and Infectious Diseases, Faculty of Medicine, School of Health Sciences, University of Ioannina, University Campus, 45110 Ioannina, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolaos-Gavriel","family":"Kolios","sequence":"additional","affiliation":[{"name":"1st Department of Internal Medicine and Infectious Diseases, Faculty of Medicine, School of Health Sciences, University of Ioannina, University Campus, 45110 Ioannina, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6131-5634","authenticated-orcid":false,"given":"Dimitrios","family":"Biros","sequence":"additional","affiliation":[{"name":"1st Department of Internal Medicine and Infectious Diseases, Faculty of Medicine, School of Health Sciences, University of Ioannina, University Campus, 45110 Ioannina, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleni-Dimitra","family":"Oikonomidi","sequence":"additional","affiliation":[{"name":"1st Department of Internal Medicine and Infectious Diseases, Faculty of Medicine, School of Health Sciences, University of Ioannina, University Campus, 45110 Ioannina, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8900-0212","authenticated-orcid":false,"given":"Maria","family":"Lagadinou","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Medical School, University of Patras, 26504 Patras, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexia","family":"Papalexandrou","sequence":"additional","affiliation":[{"name":"1st Department of Internal Medicine and Infectious Diseases, Faculty of Medicine, School of Health Sciences, University of Ioannina, University Campus, 45110 Ioannina, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3958-2266","authenticated-orcid":false,"given":"Haralampos","family":"Milionis","sequence":"additional","affiliation":[{"name":"1st Department of Internal Medicine and Infectious Diseases, Faculty of Medicine, School of Health Sciences, University of Ioannina, University Campus, 45110 Ioannina, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8152-6367","authenticated-orcid":false,"given":"Eirini","family":"Christaki","sequence":"additional","affiliation":[{"name":"1st Department of Internal Medicine and Infectious Diseases, Faculty of Medicine, School of Health Sciences, University of Ioannina, University Campus, 45110 Ioannina, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgios","family":"Kalambokis","sequence":"additional","affiliation":[{"name":"1st Department of Internal Medicine and Infectious Diseases, Faculty of Medicine, School of Health Sciences, University of Ioannina, University Campus, 45110 Ioannina, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1038\/s41575-023-00759-2","article-title":"Global epidemiology of cirrhosis\u2014Aetiology, trends and predictions","volume":"20","author":"Huang","year":"2023","journal-title":"Nat. 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