In-depth investigation of the mechanisms of Echinacea purpurea polysaccharide mitigating alcoholic liver injury in mice via gut microbiota informatics and liver metabolomics

Accumulating evidence suggests that the pathogenesis of alcoholic liver disease (ALD) is strongly correlated with abnormalities of the gut-liver axis. Echinacea purpurea polysaccharide (EPP) is a homogeneous polysaccharide, which has been shown to mitigate ALD. However, the effects of EPP on gut microbiome and consequently on hepatic metabolism have yet to be explored. In this study, the microbiome and metabolomics were combined to explore the effects of EPP on gut microbiota and hepatic metabolism, and the relationship between both was further revealed by Spearman correlation analysis. Results exhibited EPP reversed alcohol-induced disturbances in gut microbiota, evidenced by increased abundance of Muribaculaceae, Lactobacillus, and Bacteroides and decreased abundance of Escherichia_Shigella and Enterococcus. Besides, EPP promoted the production of n-butyric acid, a short-chain fatty acid that maintains the integrity of the intestinal barrier. Moreover, EPP improved alterations in hepatic metabolites, and characteristic metabolites such as Berberine and Ponasterone as well as key metabolic pathways, particularly Nitrogen metabolism, were identified. Furthermore, correlation analysis suggested significant associations between gut microbes and hepatic metabolites, which in turn confirmed EPP alleviated ALD via the gut-liver axis. Therefore, these findings elucidated in-depth mechanisms of EPP against ALD and provided a new target for intervention in alcohol-related diseases.