Non-ethanol components of Baijiu alleviate ethanol-induced energy metabolism disorder and gut microbiota dysbiosis in mice

Abstract

Energy and gut-liver metabolic disorders are critical events in alcohol-related diseases. However, the specific mechanisms by which they mediate the differential effects between Chinese Baijiu and ethanol remain largely unknown. As a traditional Chinese fermented beverage, Baijiu contains abundant non-ethanol components in addition to ethanol. In this study, we conducted a multi-dimensional assessment of the ameliorative effects and underlying mechanisms of non-ethanol components from Baijiu against ethanol-induced liver injury using animal experiments, serum metabolomics, 16S rRNA sequencing of gut microbiota, and in vitro cell assays. The results showed that non-ethanol components of Baijiu significantly alleviated ethanol-induced body weight loss and hepatic pathological damage in mice, reduced serum AST and ALT activities as well as hepatic MDA levels, and enhanced the activity of the mitochondrial antioxidant enzyme SOD2. Furthermore, these components restored 92 ethanol-dysregulated metabolites, targeted the tricarboxylic acid cycle and glycolysis pathways, and re-established the intracellular NADH/NAD⁺ redox balance. Concurrently, they remodeled the gut microbial structure, restored the Firmicutes/Bacteroidetes (F/B) ratio, inhibited the abnormal proliferation of g_Ligilactobacillus, and reduced lactate production. Cellular experiments confirmed that excessive lactate exacerbated oxidative stress. The non-ethanol extract of Baijiu exhibited relief activity against ethanol-induced liver injury, and multiple active chemical constituents were identified in this extract via GC-MS. In conclusion, non-ethanol components of Baijiu alleviate alcoholic liver injury through regulating energy metabolism homeostasis and remodeling gut microecology. These findings provide a scientific basis for the prevention and treatment of alcoholic liver disease and the development of bioactive ingredients.