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Coumarin induces hepatotoxicity, but the inflammatory mechanism of coumarin is unclear. Here, we explored the effects of coumarin on systemic and hepatic inflammation. Our study found that coumarin reduced the abundance of\n                      <jats:italic toggle=\"yes\">Akkermansia muciniphila<\/jats:italic>\n                      . The number of colonic goblet cells and the expression of\n                      <jats:italic toggle=\"yes\">Claudin 1<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">ZO-1<\/jats:italic>\n                      were decreased in coumarin-treated groups, increasing intestinal permeability. Coumarin elevated the expression of lipopolysaccharide (LPS) biosynthesis genes and serum LPS. These changes increased oxidative stress indicators and total BA (TBA) in the liver. Coumarin inhibited\n                      <jats:italic toggle=\"yes\">Fxr<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">Shp<\/jats:italic>\n                      expressions in the liver, thereby promoting cholesterol 7-alpha hydroxylase (\n                      <jats:italic toggle=\"yes\">Cyp7a1<\/jats:italic>\n                      ) transcription and upregulating TBA level. Collectively, coumarin induced systemic and hepatic inflammation by decreasing tight junction protein and colonic goblet cells, increasing LPS biosynthesis genes of gut microbiota and serum LPS, and elevating TBA level via the\n                      <jats:italic toggle=\"yes\">Fxr-Shp<\/jats:italic>\n                      pathway.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        Coumarin, a compound found in\n                        <jats:italic toggle=\"yes\">Melilotus officinalis<\/jats:italic>\n                        , a high-quality forage plant crucial to animal husbandry, has raised safety concerns due to its potential for severe animal poisoning and liver toxicity. It is not clear about the mechanism of coumarin-induced systemic inflammation and liver inflammation. This research aims to elucidate the mechanisms of coumarin-induced systemic and hepatic inflammation, which is of significant importance for the development of agriculture and animal husbandry. In agriculture, understanding how coumarin affects the gut microbiota and intestinal barrier function could lead to the development of new varieties of\n                        <jats:italic toggle=\"yes\">Melilotus officinalis<\/jats:italic>\n                        with lower coumarin concentrations, thus improving its safety as a forage crop.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/spectrum.01415-25","type":"journal-article","created":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T13:00:43Z","timestamp":1758286843000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":3,"title":["Increased intestinal permeability and bile acid accumulation via inhibition of the FXR-SHP pathway contribute to coumarin-induced systemic inflammation"],"prefix":"10.1128","volume":"13","author":[{"given":"Na","family":"Shou","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01mkqqe32","id-type":"ROR","asserted-by":"publisher"}],"name":"State Key Laboratory of Herbage Improvement and Grassland Agro-ecosystems, Center for Grassland Microbiome, College of Pastoral Agriculture Science and Technology, Lanzhou University","place":["Lanzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dandan","family":"Wu","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01mkqqe32","id-type":"ROR","asserted-by":"publisher"}],"name":"State Key Laboratory of Herbage Improvement and Grassland Agro-ecosystems, Center for Grassland Microbiome, College of Pastoral Agriculture Science and Technology, Lanzhou University","place":["Lanzhou, 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