{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:42:36Z","timestamp":1786977756913,"version":"build-2736575974"},"reference-count":38,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","license":[{"start":{"date-parts":[[2020,3,10]],"date-time":"2020-03-10T00:00:00Z","timestamp":1583798400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2020,3,10]],"date-time":"2020-03-10T00:00:00Z","timestamp":1583798400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2020,5]]},"abstract":"<jats:sec>\n                    <jats:title>Background and Aims<\/jats:title>\n                    <jats:p>Microbial dysbiosis is associated with alcohol\u2010related hepatitis (AH), with the mechanisms yet to be elucidated. The present study aimed to determine the effects of alcohol and zinc deficiency on Paneth cell (PC) antimicrobial peptides, \u03b1\u2010defensins, and to define the link between PC dysfunction and AH.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Approach and Results<\/jats:title>\n                    <jats:p>\n                      Translocation of pathogen\u2010associated molecular patterns (PAMPs) was determined in patients with severe AH and in a mouse model of alcoholic steatohepatitis. Microbial composition and PC function were examined in mice. The link between \u03b1\u2010defensin dysfunction and AH was investigated in \u03b1\u2010defensin\u2010deficient mice. Synthetic human \u03b1\u2010defensin 5 (HD5) was orally given to alcohol\u2010fed mice to test the therapeutic potential. The role of zinc deficiency in \u03b1\u2010defensin was evaluated in acute and chronic mouse models of zinc deprivation. Hepatic inflammation was associated with PAMP translocation and lipocalin\u20102 (LCN2) and chemokine (C\u2010X\u2010C motif) ligand 1 (CXCL1) elevation in patients with AH. Antibiotic treatment, lipopolysaccharide injection to mice, and\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      experiments showed that PAMPs, but not alcohol, directly induced LCN2 and CXCL1. Chronic alcohol feeding caused systemic dysbiosis and PC \u03b1\u2010defensin reduction in mice. Knockout of functional \u03b1\u2010defensins synergistically affected alcohol\u2010perturbed bacterial composition and the gut barrier and exaggerated PAMP translocation and liver damage. Administration of HD5 effectively altered cecal microbial composition, especially increased\n                      <jats:italic toggle=\"yes\">Akkermansia muciniphila<\/jats:italic>\n                      , and reversed the alcohol\u2010induced deleterious effects. Zinc\u2010regulated PC homeostasis and \u03b1\u2010defensins function at multiple levels, and dietary zinc deficiency exaggerated the deleterious effect of alcohol on PC bactericidal activity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Taken together, the study suggests that alcohol\u2010induced PC \u03b1\u2010defensin dysfunction is mediated by zinc deficiency and involved in the pathogenesis of AH. HD5 administration may represent a promising therapeutic approach for treating AH.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/hep.30945","type":"journal-article","created":{"date-parts":[[2019,9,14]],"date-time":"2019-09-14T07:03:26Z","timestamp":1568444606000},"page":"1575-1591","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":73,"title":["Paneth Cell Dysfunction Mediates Alcohol\u2010related Steatohepatitis Through Promoting Bacterial Translocation in Mice: Role of Zinc Deficiency"],"prefix":"10.1097","volume":"71","author":[{"given":"Wei","family":"Zhong","sequence":"first","affiliation":[{"name":"Center for Translational Biomedical Research,University of North Carolina at Greensboro,North Carolina Research Campus,Kannapolis,NC"},{"name":"Department of Nutrition,University of North Carolina at Greensboro,North Carolina Research 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