Microbiome-Metabolome Analysis Insight into the Effects of the Extract of Phyllanthus emblica L. on High-Fat Diet-Induced Hyperlipidemia.

ABSTRACT

The fruit of Phyllanthus emblica L. (FEPE) has a long history of use in Asian folk medicine. The main bioactive compounds in FEPE are polyphenols, known for their potent antioxidant, anti-inflammatory, and hypolipidemic activities. The present study aimed to investigate the intervention effect of FEPE (100 and 200 mg/kg) on hyperlipidemia for 8 weeks and preliminarily explored the potential mechanism by microbiome-metabolome analysis. The results showed that a high-dose FEPE (200 mg/kg) effectively alleviated dyslipidaemic symptoms and body weight gain in hyperlipidemic mice induced by a high-fat diet (HFD). Microbiome analysis showed that FEPE altered the structure of the intestinal microbiota, which included an increase in specific probiotics (such as Akkermansia, Anaerovorax, and Bacteroides) and a decrease in harmful bacteria (including A2, Acetitomaculum, Candidatus_Arthromitus, Lachnospiraceae_NK4A136_group, Lachnospiraceae_NK4B4_group, Rikenella, and Streptococcus), as well as a reduction in the level of short-chain fatty acids (SCFAs). In addition, significant changes in the hepatic metabolome were observed, and eight key metabolites associated with betaine metabolism, lysine degradation, methionine metabolism, and fatty acid metabolism pathways were primarily filtered. The correlated analysis identified several key "microbiota-metabolite" axes in the treatment of hyperlipidemia by FEPE extract. In conclusion, the present study is expected to provide a basis for treating hyperlipidemia with FEPE from the perspective of the microbiome-liver metabolome axis.