Alcoholic liver disease and intestinal microbiota in an experimental model: Biochemical, inflammatory, and histologic parameters

• Published in: Nutrition (Burbank, Los Angeles County, Calif.) Vol. 106; p. 111888
• Main Authors: Thoen, Rutiane Ullmann, Longo, Larisse, Leonhardt, Luiza Cecília, Pereira, Matheus Henrique Mariano, Rampelotto, Pabulo Henrique, Cerski, Carlos Thadeu Schmidt, Álvares-da-Silva, Mário Reis
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-02-2023; Elsevier Limited
• Subjects: Alanine; Albumin; Albumins; Alcoholic liver disease; Alcoholism; Animal model; Animal models; Animals; Aspartate transaminase; Biochemistry; Carbohydrates; Cholesterol; Diet; Digestive system; Ethanol; Ethanol - metabolism; Experiments; Fatty liver; Fatty Liver - metabolism; Gastrointestinal Microbiome - genetics; Gastrointestinal tract; Gene expression; High density lipoprotein; High fat diet; intestinal microbiota; Intestinal microflora; Laboratory animals; Lipids; Liver; Liver - metabolism; Liver diseases; Liver Diseases, Alcoholic - metabolism; Liver Diseases, Alcoholic - microbiology; Male; Microbiota; Proteins; Rats; Rats, Wistar; Relative abundance; Saccharin; Saccharin - metabolism; Steatosis; Therapeutic targets; Transaminase; Transaminases; Transaminases - metabolism; Triglycerides; Womens health; Brazil; United States > US; Animal model; intestinal microbiota; Alcoholic liver disease
• ISSN: 0899-9007; 1873-1244
• DOI: 10.1016/j.nut.2022.111888

•Alcoholic liver disease (ALD) is the leading cause of alcohol-related deaths worldwide.•The standard of care for patients with ALD has not changed in the last several decades. It is still based on alcohol abstention, yet the mortality of patients with alcoholic hepatitis remains high.•This demonstrates a major gap in development of new therapies and highlights the lack of attention to patients with alcoholic hepatitis.•Limited experimental models make the development of new therapies difficult.•The model discussed here is capable of inducing ALD in early stages with biochemical, histopathologic, and intestinal microbiota composition changes, allowing the study of pathophysiologic mechanisms and new therapeutic strategies.
Alcoholic liver disease (ALD) is the leading cause of alcohol-related deaths worldwide. Experimental ALD models are expensive and difficult to reproduce. A low-cost, reproducible ALD model was developed, and liver damage compared with the gut microbiota. The aims of this study were to develop an experimental model of ALD, through a high-fat diet, the chronic use of ethanol, and intragastric alcohol binge; and to evaluate the composition of the gut microbiota and its correlation with markers of inflammatory and liver disease progression in this model.
Adult male Wistar rats were randomized (N = 24) to one of three groups: control (standard diet and water + 0.05% saccharin), ALC4 and ALC8 (sunflower seed, 10% ethanol + 0.05% saccharin for 4 and 8 wk, respectively). On the last day, ALC4/8 received alcoholic binge (5 g/kg). Clinical, nutritional, biochemical, inflammatory, pathologic, and gut microbiota data were analyzed.
ALC4/8 animals consumed more alcohol and lipids (P < 0.01) and less total energy, liquids, solids, carbohydrates, and proteins (P < 0.01), and gained less weight (P < 0.01) than controls. ALC8 had lower Lee index scores than controls and ALC4 (P < 0.01). Aminotransferases increased and albumin diminished in ALC4/8 but not in the control group (P < 0.03 for all). Glucose and aspartate transaminase/alanine aminotransaminase ratios were higher in the ALC8 rats than in the controls (P < 0.03). Cholesterol was higher in ALC4 and lower in ALC8 compared with controls (P < 0.03). Albumin and high-density lipoprotein cholesterol levels were lower in ALC8 (P < 0.03). Hepatic concentration of triacylglycerols was higher in ALC8 than in ALC4 and controls (P < 0.05). ALC4/8 presented microvesicular grade 2 and 3 steatosis, respectively, and macrovesicular grade 1. No change in the gene expression of inflammatory markers between groups was seen. ALC4/8 had lower fecal bacterial α-diversity and relative abundance of Firmicutes (P < 0.005) and greater Bacterioidetes (P < 0.0007) and Protobacteria (P < 0.001) than controls. Gut microbiota correlated with serum and liver lipids, steatosis, albumin, and aminotransferases (P < 0.01 for all).
The model induced nutritional, biochemical, histologic, and gut microbiota changes, and appears to be useful in the study of therapeutic targets.