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The objective of this study was to evaluate whether polyhydroxylated bile acids (BAs), known to protect mice from the development of acquired cholestatic liver injury, counteract <jats:italic>S. mansoni<\/jats:italic>\u2010induced inflammation and fibrosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Adult FVB\/N wild type (WT) and <jats:italic>Abcb11<\/jats:italic>\/<jats:italic>Bsep<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> mice were infected with either 25 or 50 <jats:italic>S. mansoni<\/jats:italic> cercariae. Eight weeks post infection, effects on liver histology, serum biochemistry, gene expression profile of proinflammatory cytokines and fibrotic markers, hepatic hydroxyproline content and FACS analysis were performed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p><jats:italic>Bsep<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> mice infected with <jats:italic>S. mansoni<\/jats:italic> showed significantly less hepatic inflammation and tendentially less fibrosis compared to infected WT mice. Despite elevated alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase levels in infected <jats:italic>Bsep<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> mice, inflammatory cells such as M2 macrophages and Mac\u20102\/galectin\u20103<jats:sup>+<\/jats:sup> cells were reduced in these animals. Accordingly, mRNA\u2010expression levels of anti\u2010inflammatory cytokines (IL\u20104 and IL\u201013) were increased in <jats:italic>Bsep<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> mice upon infection. Furthermore, infected <jats:italic>Bsep<jats:sup>\u2212\/\u2212<\/jats:sup><\/jats:italic> mice exhibited decreased hepatic egg load and parasite fecundity, consequently affecting the worm reproduction rate. This outcome could arise from elevated serum BA levels and lower blood pH in <jats:italic>Bsep<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The loss of <jats:italic>Bsep<\/jats:italic> and the resulting changes in bile acid composition and blood pH are associated with the reduction of parasite fecundity, thus attenuating the development of <jats:italic>S. mansoni<\/jats:italic>\u2010induced hepatic inflammation and fibrosis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.15710","type":"journal-article","created":{"date-parts":[[2023,8,29]],"date-time":"2023-08-29T08:02:30Z","timestamp":1693296150000},"page":"2469-2478","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["<i>Bsep\/Abcb11<\/i> knockout ameliorates <i>Schistosoma mansoni<\/i> liver pathology by reducing parasite 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