{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,15]],"date-time":"2026-02-15T04:11:42Z","timestamp":1771128702584,"version":"3.50.1"},"reference-count":49,"publisher":"Wiley","issue":"11-12","license":[{"start":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T00:00:00Z","timestamp":1765843200000},"content-version":"vor","delay-in-days":45,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["U22A20275"],"award-info":[{"award-number":["U22A20275"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82370627"],"award-info":[{"award-number":["82370627"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100017950","name":"Shanghai Municipal Health Commission","doi-asserted-by":"publisher","award":["202340185"],"award-info":[{"award-number":["202340185"]}],"id":[{"id":"10.13039\/100017950","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2023M732649"],"award-info":[{"award-number":["2023M732649"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Digest Diseases"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Metabolic dysfunction\u2013associated steatotic liver disease (MASLD) represents a major global health burden, yet its underlying mechanisms remain incompletely defined. We aimed to investigate the role of intestinal NOD\u2010, LRR\u2010, and pyrin\u2010domain\u2010containing protein 3 (NLRP3) inflammasome in the gut\u2013liver axis to identify potential therapeutic targets for MASLD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Eight\u2010week\u2010old male mice were given a methionine\u2010choline\u2010deficient (MCD) diet for 4\u2009weeks to induce MASLD\u2010associated fibrosis. The functional role of NLRP3 was assessed using\n                      <jats:italic>Vil1<\/jats:italic>\n                      <jats:sup>cre<\/jats:sup>\n                      <jats:italic>Nlrp3<\/jats:italic>\n                      <jats:sup>f\/f<\/jats:sup>\n                      mice with intestinal epithelial cell\u2010specific\n                      <jats:italic>Nlrp3<\/jats:italic>\n                      deletion. To evaluate the potential influence of the gut microbiota,\n                      <jats:italic>Vil1<\/jats:italic>\n                      <jats:sup>cre<\/jats:sup>\n                      <jats:italic>Nlrp3<\/jats:italic>\n                      <jats:sup>f\/f<\/jats:sup>\n                      \u2010MCD mice were co\u2010housed with\n                      <jats:italic>Nlrp3<\/jats:italic>\n                      <jats:sup>f\/f<\/jats:sup>\n                      \u2010MCD counterparts. The effect of butyrate was also evaluated in\n                      <jats:italic>Vil1<\/jats:italic>\n                      <jats:sup>cre<\/jats:sup>\n                      <jats:italic>Nlrp3<\/jats:italic>\n                      <jats:sup>f\/f<\/jats:sup>\n                      \u2010MCD mice via oral gavage for 3\u2009weeks. The role of intestinal NLRP3 was further validated in a carbon tetrachloride (CCl\n                      <jats:sub>4<\/jats:sub>\n                      )\u2010induced liver fibrosis model.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Intestinal NLRP3 expression was markedly reduced in wild\u2010type mice given MCD diet. Compared with\n                      <jats:italic>Nlrp3<\/jats:italic>\n                      <jats:sup>f\/f<\/jats:sup>\n                      \u2010MCD mice,\n                      <jats:italic>Vil1<\/jats:italic>\n                      <jats:sup>cre<\/jats:sup>\n                      <jats:italic>Nlrp3<\/jats:italic>\n                      <jats:sup>f\/f<\/jats:sup>\n                      \u2010MCD mice developed more severe MASLD and exhibited impaired intestinal barrier integrity, whereas the co\u2010housing condition alleviated hepatic pathology. Moreover, butyrate administration significantly improved hepatic steatosis and fibrosis in\n                      <jats:italic>Vil1<\/jats:italic>\n                      <jats:sup>cre<\/jats:sup>\n                      <jats:italic>Nlrp3<\/jats:italic>\n                      <jats:sup>f\/f<\/jats:sup>\n                      \u2010MCD mice. Mechanistic analysis revealed attenuated hepatic peroxisome proliferator\u2010activated receptor \u03b1 (PPAR\u03b1) activation and enhanced hepatic activator protein (AP)\u20101 signaling in\n                      <jats:italic>Vil1<\/jats:italic>\n                      <jats:sup>cre<\/jats:sup>\n                      <jats:italic>Nlrp3<\/jats:italic>\n                      <jats:sup>f\/f<\/jats:sup>\n                      \u2010MCD mice, both of which improved under co\u2010housing condition or butyrate treatment. Similarly, intestinal\n                      <jats:italic>Nlrp3<\/jats:italic>\n                      deletion aggravated CCl\n                      <jats:sub>4<\/jats:sub>\n                      \u2010induced liver fibrosis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Loss of intestinal\n                      <jats:italic>Nlrp3<\/jats:italic>\n                      diminished butyrate production, inhibited PPAR\u03b1 expression, and enhanced AP\u20101 signaling, collectively intensifying MASLD progression.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/1751-2980.70022","type":"journal-article","created":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T14:16:05Z","timestamp":1765894565000},"page":"544-558","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Intestinal\n                    <scp>NLRP3<\/scp>\n                    Deficiency Exacerbates\n                    <scp>MASLD<\/scp>\n                    in Male Mice via Reduced Butyrate Production"],"prefix":"10.1111","volume":"26","author":[{"given":"Li","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Tongji Hospital, School of Medicine Tongji University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Tongji Hospital, School of Medicine Tongji University  Shanghai 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