Multi-omics reveals that gut microbiota-derived taurodeoxycholic acid mediates the protective effect of Lactobacillus rhamnosus GG against LPS-induced liver injury

GG (LGG) alleviated LPS-induced inflammation and liver injury while restoring hepatic conjugated secondary bile acids, particularly taurodeoxycholic acid (TDCA). The regulatory effect of LGG on hepatic conjugated secondary bile acids was associated with enhanced ileal bile acid reabsorption and a balanced gut microbiota composition. Notably, the hepatoprotective effects were abolished by heat-killed LGG or by co-treatment with caffeic acid phenethyl ester, which diminished LGG's activity in the intestine. TDCA treatment alleviated LPS-induced hepatic inflammation in part through modulation of the oxidative phosphorylation pathway. Collectively, these findings identify disrupted bile acid metabolism as a key event in LPS-induced liver injury and highlight the modulation of TDCA metabolism by probiotics as a promising therapeutic target for endotoxin-related disorders.