{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T03:53:53Z","timestamp":1788580433387,"version":"build-2803163510"},"reference-count":49,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,2,17]],"date-time":"2023-02-17T00:00:00Z","timestamp":1676592000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"JSPS KAKENHI","award":["22K07005"],"award-info":[{"award-number":["22K07005"]}]},{"name":"Toyama Pharmaceutical Valley Development Consortium","award":["22K07005"],"award-info":[{"award-number":["22K07005"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The potential roles of the gut microbiota in the pathogenesis of non-alcoholic fatty liver disease, including non-alcoholic steatohepatitis (NASH), have attracted increased interest. We have investigated the links between gut microbiota and NASH development in Tsumura-Suzuki non-obese mice fed a high-fat\/cholesterol\/cholate-based (iHFC) diet that exhibit advanced liver fibrosis using antibiotic treatments. The administration of vancomycin, which targets Gram-positive organisms, exacerbated the progression of liver damage, steatohepatitis, and fibrosis in iHFC-fed mice, but not in mice fed a normal diet. F4\/80+-recruited macrophages were more abundant in the liver of vancomycin-treated iHFC-fed mice. The infiltration of CD11c+-recruited macrophages into the liver, forming hepatic crown-like structures, was enhanced by vancomycin treatment. The co-localization of this macrophage subset with collagen was greatly augmented in the liver of vancomycin-treated iHFC-fed mice. These changes were rarely seen with the administration of metronidazole, which targets anaerobic organisms, in iHFC-fed mice. Finally, the vancomycin treatment dramatically modulated the level and composition of bile acid in iHFC-fed mice. Thus, our data demonstrate that changes in inflammation and fibrosis in the liver by the iHFC diet can be modified by antibiotic-induced changes in gut microbiota and shed light on their roles in the pathogenesis of advanced liver fibrosis.<\/jats:p>","DOI":"10.3390\/ijms24044050","type":"journal-article","created":{"date-parts":[[2023,2,17]],"date-time":"2023-02-17T03:27:41Z","timestamp":1676604461000},"page":"4050","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Impact of Vancomycin Treatment and Gut Microbiota on Bile Acid Metabolism and the Development of Non-Alcoholic Steatohepatitis in Mice"],"prefix":"10.3390","volume":"24","author":[{"given":"Kaichi","family":"Kasai","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Engineering, Faculty of Engineering, Toyama Prefectural University, 5180 Kurokawa, Imizu 939-0398, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoya","family":"Igarashi","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Engineering, Faculty of Engineering, Toyama Prefectural University, 5180 Kurokawa, Imizu 939-0398, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Tada","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Engineering, Faculty of Engineering, Toyama Prefectural University, 5180 Kurokawa, Imizu 939-0398, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koudai","family":"Kani","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Engineering, Faculty of Engineering, Toyama Prefectural University, 5180 Kurokawa, Imizu 939-0398, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shun","family":"Takano","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Engineering, Faculty of Engineering, Toyama Prefectural University, 5180 Kurokawa, Imizu 939-0398, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsutomu","family":"Yanagibashi","sequence":"additional","affiliation":[{"name":"Toyama Prefectural Institute for Pharmaceutical Research, 17-1 Nakataikouyama, Imizu 939-0363, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fumitake","family":"Usui-Kawanishi","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Engineering, Faculty of Engineering, Toyama Prefectural University, 5180 Kurokawa, Imizu 939-0398, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiho","family":"Fujisaka","sequence":"additional","affiliation":[{"name":"First Department of Internal Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, 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