Microbiome and Lipidomics Reveal the Mechanism of Eight Zhes Decoction on MAFLD

The therapeutic potential of Eight Zhes Decoction (EZD) against metabolic dysfunction-associated fatty liver disease (MAFLD) is well-recognized; however, the underlying biological pathways are not well understood. To address this gap, an integrated investigation using both lipidomics and metagenomics was conducted to reveal the mechanistic rationale behind the effects of EZD.

A MAFLD mouse model was established using a Methionine-Choline-Deficient (MCD) diet combined with CCl₁. The mice were treated with EZD for four weeks. Hepatic injury was assessed via H&E, Oil Red O, and Masson staining. Untargeted hepatic lipidomics and shotgun metagenomics were employed to profile lipid species and the gut microbiota composition, respectively.

Histopathological analysis confirmed that EZD significantly alleviated hepatic steatosis, ballooning degeneration, and fibrosis. Lipidomics identified 277 differential lipids; EZD treatment notably downregulated 24 TGs and modulated pathways related to arachidonic acid metabolism and bile secretion. Metagenomics revealed that EZD reshaped the gut microbiota, significantly increasing the abundance of Alistipes sp. while reducing the abundance of Faecalibaculum rodentium.

Correlation analysis demonstrated that the restored Alistipes sp. was negatively correlated with multiple hepatic TGs, whereas Faecalibaculum rodentium was positively correlated with lipid accumulation.

EZD mitigates MAFLD in mice by synergistically regulating hepatic lipid metabolism and gut microbiota. Specifically, the therapeutic effect involves restoring Alistipes sp. and modulating the gut-liver axis, providing experimental evidence for the clinical application of EZD.