{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T10:03:49Z","timestamp":1783332229852,"version":"3.54.6"},"reference-count":42,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2023,3,8]],"date-time":"2023-03-08T00:00:00Z","timestamp":1678233600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2023,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and Aims<\/jats:title><jats:p>Decompensated cirrhosis with fibrosis progression causes portal hypertension followed by an oedematous intestinal tract. These conditions weaken the barrier function against bacteria in the intestinal tract, a condition called leaky gut, resulting in invasion by bacteria and bacterial components. Here, we investigated the role of outer\u2010membrane vesicles (OMVs) of <jats:italic>Escherichia coli<\/jats:italic>, which is the representative pathogenic gut\u2010derived bacteria in patients with cirrhosis in the pathogenesis of cirrhosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We investigated the involvement of OMVs in humans using human serum and ascites samples and also investigated the involvement of OMVs from <jats:italic>E. coli<\/jats:italic> in mice using mouse liver\u2010derived cells and a mouse cirrhosis model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In vitro, OMVs induced inflammatory responses to macrophages and neutrophils, including the upregulation of C\u2010type lectin domain family 4 member E (Clec4e), and induced the suppression of albumin production in hepatocytes but had a relatively little direct effect on hepatic stellate cells. In a mouse cirrhosis model, administration of OMVs led to increased liver inflammation, especially affecting the activation of macrophages, worsening fibrosis and decreasing albumin production. Albumin administration weakened these inflammatory changes. In addition, multiple antibodies against bacterial components were increased with a progressing Child\u2010Pugh grade, and OMVs were detected in ascites of patients with decompensated cirrhosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>In conclusion, OMVs induce inflammation, fibrosis and suppression of albumin production, affecting the pathogenesis of cirrhosis. We believe that our study paves the way for the future prevention and treatment of cirrhosis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.15539","type":"journal-article","created":{"date-parts":[[2023,2,8]],"date-time":"2023-02-08T08:27:59Z","timestamp":1675844879000},"page":"1126-1140","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["<i>Escherichia coli<\/i>\u2010derived outer\u2010membrane vesicles induce immune activation and progression of cirrhosis in mice and humans"],"prefix":"10.1111","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1988-4144","authenticated-orcid":false,"given":"Kazuki","family":"Natsui","sequence":"first","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences Niigata University  Niigata 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