Propionate Ameliorates Alcohol-Induced Liver Injury in Mice via the Gut-Liver Axis: Focus on the Improvement of Intestinal Permeability

Alcohol-related liver disease (ALD) is a major cause of chronic liver disease worldwide with limited therapeuticoptions. Here, we first revealed the promising beneficial effect of gut microbiota-derived propionate on alcoholic liver injury in mice.This effect was dependent on the modulation of homeostasis of the gut-liver axis, especially the improvement of intestinalpermeability. Dietary supplementation with propionate protected against ethanol-induced loss of hepatic function and hepaticsteatosis in mice. Meanwhile, propionate treatment attenuated intestinal epithelial barrier dysfunction, restored the expression ofintestinal mucus layer components, suppressed intestinal inflammation, and altered intestinal microbiota dysbiosis, which inhibitedthe intestinal hyperpermeability and subsequently reduced lipopolysaccharide leakage in ALD mice. Furthermore, as a consequenceof endotoxemia amelioration, the liver inflammation-related TLR4-NF-Kappa B pathway was inhibited. Collectively, our results suggested that propionate supplementation may be a promising option for the prevention and treatment of ALD