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          Abstract

          Alcoholic liver disease (ALD) ranks among major causes of morbidity and mortality. Diet and crosstalk between the gut and liver are important determinants of ALD. We evaluated the effects of different types of dietary fat and ethanol on the gut microbiota composition and metabolic activity and the effect of these changes on liver injury in ALD. Compared with ethanol and a saturated fat diet (medium chain triglycerides enriched), an unsaturated fat diet (corn oil enriched) exacerbated ethanol-induced endotoxemia, liver steatosis, and injury. Major alterations in gut microbiota, including a reduction in Bacteroidetes and an increase in Proteobacteria and Actinobacteria, were seen in animals fed an unsaturated fat diet and ethanol but not a saturated fat diet and ethanol. Compared with a saturated fat diet and ethanol, an unsaturated fat diet and ethanol caused major fecal metabolomic changes. Moreover, a decrease in certain fecal amino acids was noted in both alcohol-fed groups. These data support an important role of dietary lipids in ALD pathogenesis and provide insight into mechanisms of ALD development. A diet enriched in unsaturated fats enhanced alcohol-induced liver injury and caused major fecal metagenomic and metabolomic changes that may play an etiologic role in observed liver injury. Dietary lipids can potentially serve as inexpensive interventions for the prevention and treatment of ALD.

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          Author and article information

          Contributors
          Journal
          Am J Pathol
          Am. J. Pathol
          The American Journal of Pathology
          American Society for Investigative Pathology
          0002-9440
          1525-2191
          1 April 2017
          April 2016
          : 186
          : 4
          : 765-776
          Affiliations
          []Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, University of Louisville School of Medicine, Louisville, Kentucky
          []Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, Kentucky
          [∗∗ ]Department of Chemistry, University of Louisville School of Medicine, Louisville, Kentucky
          []Baylor Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas
          [§ ]Alkek Center for Metagenomics and Microbiome Research, Baylor College of Medicine, Houston, Texas
          []College of Food Science and Engineering, Jilin Agricultural University, Changchun, China
          []School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China
          [†† ]Robley Rex Veterans Medical Center, Louisville, Kentucky
          Author notes
          []Address correspondence to Irina A. Kirpich, M.P.H., Ph.D., Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, University of Louisville, Louisville, KY 40202.Division of Gastroenterology, Hepatology, and NutritionDepartment of MedicineUniversity of LouisvilleLouisvilleKY40202 i0kirp01@ 123456louisville.edu
          Article
          PMC5808146 PMC5808146 5808146 S0002-9440(16)00019-5
          10.1016/j.ajpath.2015.11.017
          5808146
          27012191
          47e17a35-2238-4686-b1ec-0a619727fe21
          © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.
          History
          : 17 November 2015
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