Transcriptomic Profiling Identifies Novel Hepatic and Intestinal Genes Following Chronic Plus Binge Ethanol Feeding in Mice.

BACKGROUND: Alcohol-associated liver disease accounts for half of cirrhosis-related deaths worldwide. The spectrum of disease varies from simple steatosis to fibrosis, cirrhosis and ultimately hepatocellular carcinoma. Understanding the disease on a molecular level helps us to develop therapeutic targets. AIM: We performed transcriptomic analysis in liver and ileum from chronic plus binge ethanol-fed mice, and we assessed the role of selected differentially expressed genes and their association with serum bile acids and gut microbiota. METHODS: Wild-type mice were subjected to a chronic Lieber-DeCarli diet model for 8 weeks followed by one binge of ethanol. RNA-seq analysis was performed on liver and ileum samples. Associations between selected differentially regulated genes and serum bile acid profile or fecal bacterial profiling (16S rDNA sequencing) were investigated. RESULTS: We provide a comprehensive transcriptomic analysis to identify differentially expressed genes, KEGG pathways, and gene ontology functions in liver and ileum from chronic plus binge ethanol-fed mice. In liver, we identified solute carrier organic anion transporter family, member 1a1 (Slco1a1; encoding for organic anion transporting polypeptides (OATP) 1A1), as the most down-regulated mRNA, and it is negatively correlated with serum cholic acid level. Prokineticin 2 (Prok2) mRNA, a cytokine-like molecule associated with gastrointestinal tract inflammation, was significantly down-regulated in ethanol-fed mice. Prok2 mRNA expression was negatively correlated with abundance of Allobaculum (genus), Coprococcus (genus), Lachnospiraceae (family), Lactococcus (genus), and Cobriobacteriaceae (family), while it positively correlated with Bacteroides (genus). CONCLUSIONS: RNA-seq analysis revealed unique transcriptomic signatures in the liver and intestine following chronic plus binge ethanol feeding.