Theabrownin Alleviates Alcoholic Liver Disease in Mice by Improving Gut Microbiota and Tryptophan Metabolism

Theabrownin (TB) is a bioactive compound derived from tea. Alcoholic liver disease (ALD), caused by chronic alcohol consumption, leads to progressive liver damage associated with inflammation and steatosis. This study aimed to investigate TB's protective effects against ALD and elucidate its mechanisms. A chronic-binge ethanol feeding model was used to induce ALD in mice. Mice were administered TB alongside ethanol exposure. Liver function markers, oxidative stress parameters, inflammatory cytokines, and apoptosis indicators were evaluated. Intestinal barrier integrity and gut inflammation were assessed, along with the expression of tight junction proteins. 16S rRNA sequencing was performed to analyze gut microbiota composition. TB supplementation significantly alleviated hepatic oxidative stress and inflammation and decreased hepatocellular apoptosis. In the gut, TB mitigated ethanol-induced inflammation and restored barrier function by enhancing tight junction protein expression. Microbiota analysis revealed that TB notably increased the abundance of Akkermansia muciniphila, which was associated with altered tryptophan metabolism and activation of the aryl hydrocarbon receptor (AhR) signaling pathway. These changes contributed to the overall protective effect of TB against alcohol-induced toxicity. TB exhibits nutritionally relevant hepatoprotective effects through its antioxidant properties, enhancement of gut barrier integrity, and modulation of the gut microbiota and metabolite-mediated signaling pathways. These findings support the potential of TB as a dietary intervention for preventing or managing ALD.