Recovery of ameliorates hepatic steatosis in experimental alcohol-related liver disease.

Alcohol-related liver disease (ALD) is a major cause of liver disease and represents a global burden, as treatment options are scarce. Whereas 90% of ethanol abusers develop alcoholic fatty liver disease (AFLD), only a minority evolves to steatohepatitis and cirrhosis. Alcohol increases lipogenesis and suppresses lipid-oxidation implying steatosis, although the key role of intestinal barrier integrity and microbiota in ALD has recently emerged. () is a prominent member of human and murine intestinal microbiota, and plays important functions in metabolism, gut immunity, and mucosal barrier. We aimed to investigate the role of in the genesis of ethanol-induced liver steatosis. DNA was measured in feces of wild-type mice receiving a Lieber-DeCarli diet supplemented with an increase in alcohol concentration. In a second step, ethanol-fed mice were orally treated with living , followed by analysis of intestinal homeostasis and histological and biochemical alterations in the liver. Alcohol feeding reduced abundance, which was preserved by oral supplementation. -treated mice displayed lower hepatic steatosis and triglyceride content. restored mucosal barrier and reduced LPS translocation by enhancing mucus thickness and production of Mucin2. Furthermore, up-regulated (GLP-1) expression and restored ethanol-induced (FGF15) down-regulation. Lipid metabolism was consequently affected as administration reduced fatty acid synthesis (FA) and improved FA oxidation and lipid exportation. Moreover, treatment with preserved the mitochondrial fitness and redox state in alcohol-fed mice. In conclusion, recovery of ethanol-induced depletion by oral supplementation was associated with restored intestinal homeostasis and ameliorated experimental ALD. could serve as a novel probiotic to treat ALD in the future.