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Bile acid dysregulation is a pivotal part in their pathogenesis. The aim of this study was to evaluate the bile acid sequestrant colesevelam in a microbiome-humanized mouse model of diet-induced obesity and steatohepatitis.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Germ-free C57BL\/6 mice were associated with stool from patients with NASH and subjected to 20\u00a0weeks of Western diet feeding with and without colesevelam.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Colesevelam reduced Western diet-induced body and liver weight gain in microbiome-humanized mice compared with controls. It ameliorated Western diet-induced hepatic inflammation, steatosis, fibrosis and insulin resistance. Colesevelam increased de novo bile acid synthesis and decreased hepatic cholesterol content in microbiome-humanized mice fed a Western diet. It further induced the gene expression of the antimicrobials <jats:italic>Reg3g<\/jats:italic> and <jats:italic>Reg3b<\/jats:italic> in the distal small intestine and decreased plasma levels of LPS.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Colesevelam ameliorates Western diet-induced steatohepatitis and obesity in microbiome-humanized mice.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s12072-022-10296-w","type":"journal-article","created":{"date-parts":[[2022,1,24]],"date-time":"2022-01-24T17:02:39Z","timestamp":1643043759000},"page":"359-370","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Colesevelam ameliorates non-alcoholic steatohepatitis and obesity in mice"],"prefix":"10.1007","volume":"16","author":[{"given":"Phillipp","family":"Hartmann","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Duan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukiko","family":"Miyamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00fcnevver","family":"Demir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonja","family":"Lang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elda","family":"Hasa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Stern","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis","family":"Yamashita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary","family":"Conrad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Eckmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6281-825X","authenticated-orcid":false,"given":"Bernd","family":"Schnabl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,1,24]]},"reference":[{"issue":"5","key":"10296_CR1","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1038\/s41574-019-0176-8","volume":"15","author":"M Bluher","year":"2019","unstructured":"Bluher M. 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Bernd Schnabl has been consulting for Ferring Research Institute, Gelesis, HOST Therabiomics, Intercept Pharmaceuticals, Mabwell Therapeutics, Patara Pharmaceuticals and Takeda. Bernd Schnabl\u2019s institution UC San Diego has received grant support from Axial Biotherapeutics, BiomX, CymaBay Therapeutics, NGM Biopharmaceuticals, Prodigy Biotech and Synlogic Operating Company. Bernd Schnabl is founder of Nterica Bio. Patrick Stern and Mary Conrad are employees of Axial Biotherapeutics (Woburn, MA, USA). Dennis Yamashita was an employee of Axial Biotherapeutics (Woburn, MA) and is a current employee of Cambrian Biopharma (Brooklyn, NY, USA).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"All institutional and national guidelines for the care and use of laboratory animals were followed. All animal studies were reviewed and approved by the Institutional Animal Care and Use Committee at UCSD.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"Not applicable.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"Not applicable.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}}]}}