{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T13:42:52Z","timestamp":1782308572685,"version":"3.54.5"},"reference-count":49,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","license":[{"start":{"date-parts":[[2020,12,1]],"date-time":"2020-12-01T00:00:00Z","timestamp":1606780800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:sec>\n            <jats:title>Background and Aims<\/jats:title>\n            <jats:p>Mounting evidence supports an association between cholestatic liver disease and changes in the composition of the microbiome. Still, the role of the microbiome in the pathogenesis of this condition remains largely undefined.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results<\/jats:title>\n            <jats:p>To address this, we have used two experimental models, administering alpha\u2010naphtylisocyanate or feeding a 0.1% 3,5\u2010diethoxycarbonyl\u20101,4\u2010dihydrocollidine diet, to induce cholestatic liver disease in germ\u2010free mice and germ\u2010free mice conventionalized with the microbiome from wild\u2010type, specific pathogen\u2010free animals. Next, we have inhibited macrophage activation by depleting these cells using clodronate liposomes and inhibiting the inflammasome with a specific inhibitor of NOD\u2010, LRR\u2010, and pyrin domain\u2010containing protein 3. Our results demonstrate that cholestasis, the accumulation of bile acids in the liver, fails to promote liver injury in the absence of the microbiome <jats:italic toggle=\"yes\">in vivo<\/jats:italic>. Additional <jats:italic toggle=\"yes\">in vitro<\/jats:italic> studies supported that endotoxin sensitizes hepatocytes to bile\u2010acid\u2013induced cell death. We also demonstrate that during cholestasis, macrophages contribute to promoting intestinal permeability and to altered microbiome composition through activation of the inflammasome, overall leading to increased endotoxin flux into the cholestatic liver.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>We demonstrate that the intestinal microbiome contributes to cholestasis\u2010mediated cell death and inflammation through mechanisms involving activation of the inflammasome in macrophages.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.31228","type":"journal-article","created":{"date-parts":[[2020,3,13]],"date-time":"2020-03-13T18:15:25Z","timestamp":1584123325000},"page":"2090-2108","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":76,"title":["Intestinal Microbiome\u2010Macrophage Crosstalk Contributes to Cholestatic Liver Disease by Promoting Intestinal Permeability in Mice"],"prefix":"10.1097","volume":"72","author":[{"given":"Anna","family":"Isaacs\u2010Ten","sequence":"first","affiliation":[{"name":"Gut Microbes and Health Institute Strategic Programme,Quadram Institute Bioscience,Norwich Research Park,Norwich,United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Echeandia","sequence":"additional","affiliation":[{"name":"Gut Microbes and Health Institute Strategic Programme,Quadram Institute Bioscience,Norwich Research Park,Norwich,United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar","family":"Moreno\u2010Gonzalez","sequence":"additional","affiliation":[{"name":"Gut Microbes and Health Institute Strategic Programme,Quadram Institute Bioscience,Norwich Research Park,Norwich,United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arlaine","family":"Brion","sequence":"additional","affiliation":[{"name":"Analytical 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