Mechanism Of L.plantarum LP104 Improving Hyperlipidemia Through The Gut-Liver Axis

At present,the rapid development of society has brought great improvement to people’s living standards,accompanied by the increasing obesity rate year by year.Hyperlipidemia has become a high incidence disease based on obesity.The disorder of lipid metabolism caused by obesity can lead to dyslipidemia in the body,thus increasing the incidence of hyperlipidemia.In addition,hyperlipidemia can also cause other secondary cardiovascular diseases including atherosclerosis and hypertension,and the treatment of these diseases is often accompanied by huge side effects.Studies have found that probiotics have the effect of lowering blood lipid,among which Lactobacillus plantarum is lactic acid bacteria have been widely used in the food field,but the current research on its lipid lowering is only analyzed at the physiological and biochemical level,and the specific regulatory mechanism is less studied.Lactobacillus plantarum LP104 was isolated from Korean pickles by our team,it has high bile salt hydrolase activity and cholesterol degradation ability.The purpose of this study was to investigate the mechanism of L.plantarum LP104 on the regulation of hyperlipidemia in high-fat diet mice through the changes of bile acid metabolism and intestinal flora in high-fat mice.The main findings were as follows:1.The intervention of L.plantarum LP104 could significantly reduce the body weight,Lee’s index,epididymal and perirenal fat coefficient,and reduce the levels of TC,TG,LDL-C,ALT and AST in serum and liver,as well as increase the HDL-C level in serum and liver.It can also improve the glucose tolerance and insulin resistance caused by the high-fat diet,and maintain the blood glucose balance.This indicated that L.plantarum LP104 could effectively alleviate the blood lipid metabolism disorders caused by high-fat diet.2.Western blotting analyzed the protein levels of FXR,SHP,CYP7A1,CYP27A1 and HMGCR in mice liver,FXR,FGF15 and ASBT in the intestine,and found that L.plantarum LP104 was able to significantly down-regulate liver HMGCR and intestinal FXR,FGF15,up-regulate the expression of hepatic CYP7A1 and CYP27A1 protein levels.It showed that L.plantarum LP104 could alleviate hyperlipidemia caused by high-fat diet and prevent the occurrence of metabolic syndrome by inhibiting the expression of hepatic cholesterol synthesis rate-limiting enzyme HMGCR,reducing cholesterol biosynthesis,inhibiting FXR/FGF15 signaling pathway,up-regulating the protein expression of hepatic CYP7A1 and CYP27A1,and accelerating cholesterol metabolism.3.Analysis of the mouse fecal microbiota flora diversity revealed that the high-fat diet caused a significant decrease in the relative abundance of Prevotella,Akkermansia,Ruminococcaceae,Parabacteroides,Lactobacillus,Blautia,and a significant increase in the abundance of Oscillospira,Coprococcus in the mouse feces.However,Lactobacillus plantarum LP104 intervention significantly increased the abundance of Akkermansia,Lactobacillus,Blautia and significantly reduced the abundance of Coprococcus,Oscillospira,so as to regulate the imbalance of intestinal microbes.L.plantarum LP104 can restore the intestinal flora disturbance caused by high-fat diet.Conclusion: Lactobacillus plantarum LP104 can improve abnormal lipid metabolism,inhibit FXR-FGF15 signaling pathway by regulating the "gut-liver axis",promote the conversion of cholesterol to bile acid in the liver,accelerate the excretion of bile acid in feces,and alleviate hyperlipidemia induced by high-fat diet;moreover,L.plantarum LP104 can restore the intestinal flora disorders caused by high-fat diet and make it play a better role in the intestinal.