Integrative gut microbiota and metabolomics reveals the mechanism of chicory extract in improving metabolic dysfunction-associated steatotic liver disease via gut-liver axis.

BACKGROUND

Chicory (Cichorium intybus l.) has shown an efficacy anti-metabolic dysfunction-associated steatotic liver disease (MASLD) in basic research and clinical applications, but its pharmacodynamic mechanism remains unclear.

PURPOSE: This work aims to clarify the pharmacological mechanism of chicory aqueous extract (CE) in improving MASLD from the perspective of gut-liver interaction.

METHODS

MASLD mice induced by a high-fat diet were employed as the in vivo model, while palmitic acid-induced AML12 cells served as the in vitro model. Combined qRT-PCR and Western blot to detect the expression of lipid metabolism-related genes/proteins. 16S rDNA sequencing and gut microbiota depletion experiments were conducted to elucidate the CE-gut microbiota interaction. UPLC-Q-TOF-MS was employed to analyze the chemical components of CE and plasma metabolite profiles.

RESULTS

CE significantly inhibited body weight gain, improved hepatic lipid deposition, and down-regulated the expression of SREBP1 and SCD1 in MASLD mice. 16S rDNA sequencing and antibiotic-depleted microbiota experiments showed that CE significantly affected the diversity and community richness of gut microbiota, and its efficacy depended on the presence of gut microbiota. Metabolomics identified plasma taurodeoxycholic acid (TDCA) as a core metabolite of CE intervention, and its level was positively correlated with the abundance of microbial bile salt hydrolase (BSH). Furthermore, in vitro experiments confirmed that TDCA dose-dependently inhibited lipid accumulation in AML12 hyperlipidemic cells.

CONCLUSIONS

CE exerts an anti-MASLD effect by remodeling the gut microbiota to promote TDCA synthesis, thereby suppressing SREBP1/SCD1 axis. This provides a theoretical foundation for developing gut-liver axis-targeted natural therapies against MASLD.