Prevention of High-Fat-Diet-Induced Dyslipidemia by Lactobacillus plantarum LP104 through Mediating Bile Acid Enterohepatic Axis Circulation and Intestinal Flora

This work aimed to investigate the alleviative mechanism of Lactobacillus plantarum LP104 (LP104) isolated from kimchi on high-fat-diet-induced dyslipidemia by targeting the intestinal flora and bile acid (BA) metabolism. Oral administration of LP104 over 8 weeks reduced body weight gain and body fat, as well as ameliorating serum and hepatic dyslipidemia in HFD-fed C57BL/6N mice significantly. LP104 intervention also increased the ileal tauro-alpha/beta-muricholic acid sodium salt (T-alpha-MCA or T-beta- MCA) and tauroursodeoxycholic acid (TUDCA) concentrations to suppress the enterohepatic farnesoid X receptor/fibroblast growth factor 15-fibroblast growth factor receptor 4 (FXR/FGF15-FGFR4) signaling pathway, which stimulated the hepatic cholic acid (CA) and chenodeoxycholic acid (CDCA) de novo synthesis through using cholesterol. Then, LP104 treatment accelerated BA excretion with the feces and cholesterol efflux to improve HFD-caused hyperlipidemia effectively. The 16S rRNA gene high throughput sequencing revealed that LP104 promoted intestinal flora rebalance by increasing the abundances of Bacteroides, Akkermansia, Lactobacillus, and Clostridium and decreasing the abundance of Oscillospira and Coprococcus. Meanwhile, Spearman correlation analysis demonstrated that the differential flora were closely related to BA signaling molecules including CA, CDCA, T alpha-MCA, T-beta-MCA, and TUDCA after LP104 intervention. These findings provided new evidence that LP104 had the potential to be used as a naturally functional food for the prevention of dyslipidemia.

Automated summary

This study aimed to investigate the mechanism of Lactobacillus plantarum LP104 in alleviating dyslipidemia induced by a high-fat diet. The results showed that oral administration of LP104 reduced body weight gain, body fat, and serum hepatic dyslipidemia in mice. LP104 treatment increased the concentrations of certain bile acids and suppressed specific signaling pathways, leading to the synthesis of new bile acids and cholesterol efflux. Moreover, LP104 intervention promoted the rebalance of intestinal flora and its correlation with bile acid signaling molecules. These findings suggest that LP104 has the potential to be used as a natural functional food for dyslipidemia prevention.