Integrative multi-omics unravels the amelioration effects of Zanthoxylum bungeanum Maxim. on non-alcoholic fatty liver disease

Abstract

Background: The effect of Zanthoxylum bungeanum Maxim. (ZBM) on anti-obesity, lipid-lowering and liver protection has been identified, but the effect on the development of NAFLD induced by high-fat diet remains unclear.

Purpose: To evaluate the alleviation effect of ZBM on NAFLD in vivo and explore the mechanisms by analyzing the liver transcriptome, microbiota and fecal metabolites.

Methods: NAFLD model was induced in C57BL/6J mice by feeding with high-fat diet (HFD). The potential mechanism of ZBM in improving NAFLD was studied by liver transcriptome analysis, real-time PCR, immunofluorescence, 16s rRNA sequencing and non-targeted metabonomics.

Results: ZBM has alleviation effects on HFD-induced NAFLD. The liver transcriptome, real-time PCR and immunofluorescence analysis showed that ZBM could efficiently regulate fatty acid and cholesterol metabolism. The 16S rRNA sequencing and LC-MS based metabonomic demonstrated that ZBM could rebalance gut microbiota dysbiosis and regulate metabolic profiles in HFD-induced NAFLD mice. Spearman correlation analysis revealed a strong correlation between gut microbiota and biochemical, pathological indexes and differential metabolic biomarkers.

Conclusion: ZBM ameliorates HFD-induced NAFLD by regulating fatty acid and cholesterol metabolism, gut microbiota and metabolic profile.

Keywords: Gut microbiota; Liver transcriptomic; Multi-omics; Non-alcoholic fatty liver; Non-targeted metabonomic; Zanthoxylum bungeanum Maxim..