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 therapeutic options. 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 intestinal permeability. Dietary supplementation with propionate protected against ethanol-induced loss of hepatic function and hepatic steatosis in mice. Meanwhile, propionate treatment attenuated intestinal epithelial barrier dysfunction, restored the expression of intestinal mucus layer components, suppressed intestinal inflammation, and altered intestinal microbiota dysbiosis, which inhibited the intestinal hyperpermeability and subsequently reduced lipopolysaccharide leakage in ALD mice. Furthermore, as a consequence of endotoxemia amelioration, the liver inflammation-related TLR4-NF-κB pathway was inhibited. Collectively, our results suggested that propionate supplementation may be a promising option for the prevention and treatment of ALD.