Year: 2026
Type: article
Abstract: Background and Aims Excessive alcohol consumption poses a significant global health concern, ranking as the world’s 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’ (UroA), in alleviating ALD. Methods 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 in vitro. 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. Results 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 in vitro and in vivo models. Conclusion 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.
Source: Frontiers in Pharmacology
Language: English
Subfield: Pathology and Forensic Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,801
Funders: U.S. Department of Veterans Affairs, National Institutes of Health, National Institute on Alcohol Abuse and Alcoholism, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Environmental Health Sciences, National Center for Research Resources
Awards: G1829618475, G1879238788, G2401715615, G4165405249, G4583019849, G6784396132, Molecular Targets COBRE, G735709625, University of Louisville Center for Integrative Environmental Health Sciences, G9000085557, G9000233819, Hepatobiology and Toxicology COBRE, Integrated therapies for alcohol use and ALD (ITAALD) Network -UofL Clinical Center
OpenAlex ID: W7124765607