Intestinal Microbiomics and Metabolomics Insights into the Hepatoprotective Effects of Lactobacillus paracasei CCFM1222 Against the Acute Liver Injury in Mice.

Abstract

In recent years, acute liver injury (ALI) has received wide-range attention in the world due to its relatively high morbidity and mortality. This study aimed to explore the hepatoprotective effect of Lactobacillus paracasei CCFM1222 against lipopolysaccharide (LPS)-induced ALI mice and further elaborate its mechanism of action from the perspective of intestinal microbiomics and metabolomics. The results displayed that L. paracasei CCFM1222 pretreatment significantly decreased the serum ALT, and AST levels, inhibited the releases of hepatic TNF-α, IL-1β, and IL-6 levels, and activated the SOD, CAT, and GSH-Px activities in LPS-treated mice. The cecal short-chain fatty acid (SCFAs) levels were increased in LPS-treated mice with L. paracasei CCFM1222 pretreatment. In addition, L. paracasei CCFM1222 pretreatment remarkably shifted the intestinal microbiota composition, including the higher abundance of Faecalibaculum, Bifidobacterium, and lower abundance of the Prevotellaceae NK3B31 group, which is positively associated with the cecal propionic, butyric, valeric, isobutyric, and isovaleric acids. The metabolomics based on UPLC-QTOF/MS revealed that L. paracasei CCFM1222 pretreatment significantly regulated the composition of feces metabolites in LPS-treated mice, especially the potential biomarker-related butanoate metabolism, vitamin B6 metabolism, D-glutamine and D-glutamate metabolism, tryptophan metabolism, caffeine metabolism, arginine biosynthesis, arginine, and proline metabolism. Moreover, L. paracasei CCFM1222 pretreatment remarkably regulated the expression of gene-associated ALI (including Tlr4, Myd88, Nf-kβ, iNOS, Cox2, Iκ-Bα, Nrf2, and Sirt-1). In conclusion, these results suggest the possibility that L. paracasei CCFM1222 supplementation has beneficial effects on preventing the occurrence and development of ALI by inhibiting the inflammatory responses and altering intestinal microbiota composition and their metabolites.