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.Prok2mRNA expression was negatively correlated with abundance ofAllobaculum(genus),Coprococcus(genus),Lachnospiraceae(family),Lactococcus(genus), andCobriobacteriaceae(family), while it positively correlated withBacteroides(genus). Conclusions RNA-seq analysis revealed unique transcriptomic signatures in the liver and intestine following chronic plus binge ethanol feeding.