{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T09:38:13Z","timestamp":1766137093084},"reference-count":47,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2018,12,12]],"date-time":"2018-12-12T00:00:00Z","timestamp":1544572800000},"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":["Hepatology Research"],"published-print":{"date-parts":[[2019,3]]},"abstract":"<jats:sec><jats:title>Aim<\/jats:title><jats:p>Intestinal endotoxin is important for the progression of non\u2010alcoholic steatohepatitis (NASH). Circulating endotoxin levels are elevated in most animal models of diet\u2010induced non\u2010alcoholic fatty liver disease (NAFLD) and NASH. Furthermore, plasma endotoxin levels are significantly higher in NAFLD patients, which is associated with small intestinal bacterial overgrowth and increased intestinal permeability. By improving the gut microbiota environment and restoring gut\u2010barrier functions, probiotics are effective for NASH treatment in animal models. It is also widely known that hepatic fibrosis and suppression of activated hepatic stellate cells (Ac\u2010HSCs) can be attenuated using an angiotensin\u2010II type 1 receptor blocker (ARB). We thus evaluated the effect of combination probiotics and ARB treatment on liver fibrosis using a rat model of NASH.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Fisher 344 rats were fed a choline\u2010deficient\/<jats:sc>L<\/jats:sc>\u2010amino acid\u2010defined (CDAA) diet for 8\u00a0weeks to generate the NASH model. Animals were divided into ARB, probiotics, and ARB plus probiotics groups. Therapeutic efficacy was assessed by evaluating liver fibrosis, the lipopolysaccharide Toll\u2010like receptor (TLR)4 regulatory cascade, and intestinal barrier function.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Both probiotics and ARB inhibited liver fibrosis, with concomitant HSC activation and suppression of liver\u2010specific transforming growth factor\u2010\u03b2 and TLR4 expression. Probiotics reduced intestinal permeability by rescuing zonula occludens\u20101 disruption induced by the CDAA diet. Angiotensin\u2010II type 1 receptor blocker was found to directly suppress Ac\u2010HSCs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Probiotics and ARB are effective in suppressing liver fibrosis through different mechanisms. Currently both drugs are in clinical use; therefore, the combination of probiotics and ARB is a promising new therapy for NASH.<\/jats:p><\/jats:sec>","DOI":"10.1111\/hepr.13281","type":"journal-article","created":{"date-parts":[[2018,10,26]],"date-time":"2018-10-26T13:05:04Z","timestamp":1540559104000},"page":"284-295","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Combining probiotics and an angiotensin\u2010II type 1 receptor blocker has beneficial effects on hepatic fibrogenesis in a rat model of non\u2010alcoholic steatohepatitis"],"prefix":"10.1111","volume":"49","author":[{"given":"Yasuhiko","family":"Sawada","sequence":"first","affiliation":[{"name":"Third Department of Internal Medicine Nara Medical University  Kashihara Nara Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hideto","family":"Kawaratani","sequence":"additional","affiliation":[{"name":"Third Department of Internal 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