{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T14:01:31Z","timestamp":1790085691608,"version":"4.0.1"},"reference-count":94,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T00:00:00Z","timestamp":1768780800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background and Aims<\/jats:title>\n                    <jats:p>Excessive alcohol consumption poses a significant global health concern, ranking as the world\u2019s third-largest risk factor for diseases and disabilities, contributing to 5.9% of all deaths worldwide. Among various disorders linked to alcohol misuse, alcohol-associated liver disease (ALD) is the most prominent. ALD patients often exhibit increased intestinal permeability, systemic inflammation, gut dysbiosis, and hepatic steatosis. No FDA-approved therapies are available to treat ALD or to resolve the pathological domains of alcohol-induced gut barrier dysfunction, inflammation, and steatosis. The goal of this study is to investigate the potential therapeutic role of the microbial metabolite Urolithin A\u2019 (UroA), in alleviating ALD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Caco-2 (monolayer colon epithelial) cells and AML12 (hepatocytes) cells were used to test the protective activities of UroA against EtOH-induced gut barrier dysfunction and lipid accumulation\n                      <jats:italic>in vitro.<\/jats:italic>\n                      Preclinical ALD mouse models were used to test the therapeutic potential of UroA against EtOH exposure. Additionally, we generated cell-specific deletion mice with aryl hydrocarbon receptor (AHR) deletion to define the role of intestinal epithelial cell AHR in UroA-mediated protective activities against ALD.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The results presented here demonstrate the efficacy of UroA as a potential therapeutic agent to protect against EtOH-induced disruption of tight junction proteins, inflammation, and lipogenesis both\n                      <jats:italic>in vitro<\/jats:italic>\n                      and\n                      <jats:italic>in vivo<\/jats:italic>\n                      models.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our findings suggest that the simultaneous targeting of gut barrier dysfunction, inflammation, and hepatic steatosis by treatment with UroA may offer new possibilities for combating ALD. Moreover, our results suggest that UroA-mediated protective activities against EtOH-induced gut barrier dysfunction and inflammation in ALD are dependent on intestinal epithelial cell-AHR.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2025.1706111","type":"journal-article","created":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T09:14:11Z","timestamp":1768814051000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Urolithin A regulates gut: liver axis to ameliorate alcohol-associated liver disease"],"prefix":"10.3389","volume":"16","author":[{"given":"Sweta","family":"Ghosh","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Brown Cancer Center, Center for Microbiomics, Inflammation and Pathogenicity, University of Louisville","place":["Louisville, KY, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajbir","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Brown Cancer Center, Center for Microbiomics, Inflammation and Pathogenicity, University of Louisville","place":["Louisville, KY, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zachary Matthew","family":"Vanwinkle","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Brown Cancer Center, Center for Microbiomics, Inflammation and Pathogenicity, University of Louisville","place":["Louisville, KY, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig James","family":"McClain","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Louisville","place":["Louisville, KY, United States"]},{"name":"Department of Pharmacology & Toxicology, University of Louisville","place":["Louisville, KY, United States"]},{"name":"Hepatobiology & Toxicology Center, University of Louisville","place":["Louisville, KY, United States"]},{"name":"Alcohol Research Center, University of Louisville","place":["Louisville, KY, United States"]},{"name":"Robley Rex Louisville VAMC","place":["Louisville, KY, United States"]},{"name":"Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Louisville","place":["Louisville, KY, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vatsalya","family":"Vatsalya","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Louisville","place":["Louisville, KY, United States"]},{"name":"Department of Pharmacology & Toxicology, University of Louisville","place":["Louisville, KY, United States"]},{"name":"Alcohol Research Center, University of Louisville","place":["Louisville, KY, United States"]},{"name":"Robley Rex Louisville VAMC","place":["Louisville, KY, United States"]},{"name":"Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Louisville","place":["Louisville, KY, United States"]},{"name":"Clinical Laboratory for the Intervention Development of AUD and Organ Severity, University of Louisville","place":["Louisville, KY, United States"]},{"name":"NIAAA, National Institutes of Health","place":["Bethesda, MD, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bodduluri","family":"Haribabu","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Brown Cancer Center, Center for Microbiomics, Inflammation and Pathogenicity, University of Louisville","place":["Louisville, KY, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Praveen Kumar","family":"Vemula","sequence":"additional","affiliation":[{"name":"Institute for Stem Cell Biology and Regenerative Medicine (inStem), GKVK campus","place":["Bangalore, Karnataka, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Venkatakrishna Rao","family":"Jala","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Brown Cancer Center, Center for Microbiomics, Inflammation and Pathogenicity, University of Louisville","place":["Louisville, KY, United States"]},{"name":"Alcohol Research Center, University of Louisville","place":["Louisville, KY, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,1,19]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1038\/s41575-018-0099-1","article-title":"Alcohol, liver disease and the gut microbiota","volume":"16","author":"Bajaj","year":"2019","journal-title":"Nat. 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