title: Saturated and Unsaturated Dietary Fats Differentially Modulate Ethanol-Induced Changes in Gut Microbiome and Metabolome in a Mouse Model of Alcoholic Liver Disease.
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.
authors.affiliation: 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. Electronic address: i0kirp01@louisville.edu.
authors.forename: Irina A
authors.initials: IA
authors.lastname: Kirpich
authors.affiliation: 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.
authors.forename: Joseph
authors.initials: J
authors.lastname: Petrosino
authors.affiliation: 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.
authors.forename: Nadim
authors.initials: N
authors.lastname: Ajami
authors.affiliation: 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.
authors.forename: Wenke
authors.initials: W
authors.lastname: Feng
authors.affiliation: 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; College of Food Science and Engineering, Jilin Agricultural University, Changchun, China.
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Wang
authors.affiliation: 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; School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China.
authors.forename: Yanlong
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, Kentucky.
authors.forename: Juliane I
authors.initials: JI
authors.lastname: Beier
authors.affiliation: 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.
authors.forename: Shirish S
authors.initials: SS
authors.lastname: Barve
authors.affiliation: Department of Chemistry, University of Louisville School of Medicine, Louisville, Kentucky.
authors.forename: Xinmin
authors.initials: X
authors.lastname: Yin
authors.affiliation: Department of Chemistry, University of Louisville School of Medicine, Louisville, Kentucky.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Wei
authors.affiliation: Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, Kentucky; Department of Chemistry, University of Louisville School of Medicine, Louisville, Kentucky.
authors.forename: Xiang
authors.initials: X
authors.lastname: Zhang
authors.affiliation: 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; Robley Rex Veterans Medical Center, Louisville, Kentucky.
authors.forename: Craig J
authors.initials: CJ
authors.lastname: McClain
mesh_terms: D000818:Animals; D004041:Dietary Fats / Q000378:metabolism*; D004042:Dietary Fats, Unsaturated / Q000378:metabolism*; D004195:Disease Models, Animal; D000431:Ethanol / Q000494:pharmacology*; D000069196:Gastrointestinal Microbiome / Q000187:drug effects*; D008099:Liver / Q000378:metabolism; D008108:Liver Diseases, Alcoholic / Q000378:metabolism*; D008297:Male; D008810:Mice, Inbred C57BL; D014280:Triglycerides / Q000378:metabolism
chemical_list: D004041:Dietary Fats; D004042:Dietary Fats, Unsaturated; D014280:Triglycerides; D000431:Ethanol