High-dose taurine supplementation exacerbates alcohol-associated liver disease by inducing gut microbiota dysbiosis and bile acid dysregulation in mice.

BACKGROUND

β-aminoethanesulfonic acid (taurine) is a conditionally essential amino acid that plays critical roles in bile acid (BA) conjugation, antioxidative defence and metabolic regulation. Previous studies showed that faecal taurine level was reduced in patients with alcohol-associated liver disease (ALD), suggesting that taurine supplementation may have beneficial effects. This study aimed to determine whether oral taurine supplementation prevents the development of ALD in mice and to elucidate the underlying mechanisms.

METHODS

A total of 8-week-old male mice were subjected to a chronic-plus-binge ALD model. Taurine was administered orally via the diet for ten days before and during ethanol exposure. Faecal 16S ribosomal RNA metagenomic analysis, liver RNA sequencing and BA profiling were performed.

RESULTS

High-dose taurine supplementation (3 g/kg body weight/day) was associated with worsened ethanol-induced liver injury, as indicated by increased serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, hepatic steatosis, apoptosis and inflammation. At the molecular level, high-dose taurine treatment was associated with reduced Cpt1a expression, altered expression of genes involved in fatty acid β-oxidation and lipogenic gene Fasn, and decreased expression of Baat, accompanied by changes in taurine-conjugated BA profiles. These alterations were accompanied by changes in BA composition and intestinal FXR-associated gene expression. Taurine supplementation was also associated with shifts in gut microbial composition, including enrichment of hydrogen sulfide-producing bacteria, increased microbial H2S production, impaired intestinal barrier-related parameters and increased bacterial translocation to the liver, paralleling enhanced hepatic inflammatory responses. In contrast, low-dose taurine supplementation (0.2 g/kg body weight/day) was associated with improved liver phenotypes, including reduced steatosis, lower serum ALT and AST levels, decreased Fasn expression and enhanced BA conjugation. Collectively, these results indicate a dose-dependent association between taurine supplementation and ALD-related outcomes.

CONCLUSIONS

Our findings suggest that high-dose taurine supplementation is associated with unfavourable alterations in gut microbiota composition, intestinal barrier integrity, BA metabolism and hepatic taurine-related pathways in ALD, coinciding with exacerbated liver injury. In contrast, low-dose taurine supplementation was associated with improved hepatic outcomes. These results highlight the importance of dose considerations in taurine supplementation and support the concept that taurine may exert divergent effects on ALD depending on the administered dose.