Yellow tea extract ameliorates dexamethasone-induced hepatic steatosis by modulating the gut-liver axis and reshaping...

Long-term glucocorticoid therapy, exemplified by dexamethasone (DEX), frequently induces hepatic steatosis, posing a significant clinical challenge. Yellow tea (YT), a lightly fermented tea, is rich in polyphenols and polysaccharides, yet its protective effects against DEX-induced liver injury remain underexplored. This study investigated the hepatoprotective mechanisms of a yellow tea water extract (YT) using a DEX-induced mouse model, integrated with transcriptomic, metagenomic, and metabolomic analyses. YT intervention (500 mg^-1 kg^-1 day^-1 for 6 weeks) significantly attenuated DEX-induced hepatocellular injury, as evidenced by reduced serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, decreased hepatic triglyceride (TG) and total cholesterol (TC) accumulation, and suppressed systemic inflammation (lipopolysaccharide (LPS) and tumor necrosis factor-alpha (TNF-α)). Hepatic transcriptomics and subsequent reverse transcription quantitative PCR (RT-qPCR) validation revealed that YT upregulated the antioxidant genes nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) while downregulating the lipogenic gene sterol regulatory element-binding protein 1c (SREBP-1c) and upregulating the fatty acid oxidation gene peroxisome proliferator-activated receptor alpha (PPAR-α). Gut microbiota analysis showed that YT reshaped the microbial community, notably enriching beneficial taxa such as Bifidobacterium pseudolongum and members of the Muribaculaceae family. Serum metabolomics indicated that this microbiota remodeling was associated with the restoration of perturbed metabolic pathways, notably tryptophan metabolism. Correlation analysis further linked specific microbial shifts with improved metabolic and inflammatory markers. Collectively, these integrated transcriptomic, metagenomic, and metabolomic findings demonstrate that YT alleviates DEX-induced hepatic steatosis through dual mechanisms involving direct hepatic antioxidant and lipid metabolic regulation and systemic modulation via the gut-liver axis, positioning it as a promising dietary strategy against glucocorticoid-associated metabolic complications.