Shanghai Engineering Research Center of Food Microbiology, School of Medical Instrument and Food Engineering, University of Shanghai for Science and Technology, Shanghai 200093, China.
Food Funct. 2019 Mar 20;10(3):1684-1695. doi: 10.1039/c8fo02181c.
Hypercholesterolemia is closely associated with cardiovascular disease. Supplementation with probiotics has been shown to contribute to improving lipid metabolism. The probiotic mechanisms of cholesterol reduction are complicated and remain unclear. One of the potential probiotic mechanisms for cholesterol reduction is the deconjugation of bile salts. We previously found a high bile salt hydrolase (BSH) activity of Lactobacillus casei pWQH01 (overexpression of bsh1) and Lactobacillus plantarum AR113, but found no BSH activity for Lactobacillus casei LC2W in vitro. Therefore, we decided to investigate whether the high BSH activity of L. plantarum AR113 and L. casei pWQH01 could exert a cholesterol-reducing effect in vivo. Compared to the high-cholesterol diet (HCD) group, AR113 and pWQH01 groups had a significantly lower body weight (BW), serum total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) levels and atherogenic index (AI), whereas the LC2W group had a poor capability to mitigate the blood lipid levels in the hypercholesterolemic mice. In addition, the AR113 and pWQH01 groups decreased the hepatic levels of TC and LDL-C and improved hepatic steatosis compared with the HCD group. To explore their cholesterol-lowering mechanisms of action, we determined the expression levels of these genes on the cholesterol metabolic pathways. AR113 and pWQH01 groups downregulated the expression of farnesoid X receptor (FXR) and small heterodimer partner (SHP) genes, but upregulated the expression of the cholesterol 7α-hydroxylase (CYP7A1) gene in the liver. Simultaneously, the expression of cholesterol liver X receptor (LXR) and low density lipoprotein receptor (LDLR) genes was upregulated in the liver. These results indicated that L. plantarum AR113 and L. casei pWQH01 could inhibit the cholesterol absorption and accelerate the cholesterol transportation. Taken together, these findings suggest that Lactobacillus strain overexpression of bile salt hydrolase has beneficial effects against hypercholesterolemia by reducing cholesterol absorption and increasing cholesterol catabolism.
高胆固醇血症与心血管疾病密切相关。补充益生菌已被证明有助于改善脂质代谢。益生菌降低胆固醇的机制复杂且尚不清楚。降低胆固醇的潜在益生菌机制之一是胆汁盐的去共轭。我们之前发现了乳杆菌 pWQH01（bsh1 过表达）和植物乳杆菌 AR113 的高胆汁盐水解酶（BSH）活性，但在体外未发现乳杆菌 pWQH01 的 BSH 活性。因此，我们决定研究植物乳杆菌 AR113 和乳杆菌 pWQH01 的高 BSH 活性是否能在体内发挥降胆固醇作用。与高胆固醇饮食（HCD）组相比，AR113 和 pWQH01 组的体重（BW）、血清总胆固醇（TC）、低密度脂蛋白胆固醇（LDL-C）水平和致动脉粥样硬化指数（AI）均显著降低，而 LC2W 组降低高脂血症小鼠血脂水平的能力较差。此外，与 HCD 组相比，AR113 和 pWQH01 组降低了肝脏 TC 和 LDL-C 水平并改善了肝脂肪变性。为了探索其降胆固醇作用机制，我们测定了胆固醇代谢途径中这些基因的表达水平。AR113 和 pWQH01 组下调了法尼醇 X 受体（FXR）和小异二聚体伴侣（SHP）基因的表达，但上调了肝脏胆固醇 7α-羟化酶（CYP7A1）基因的表达。同时，肝脏中胆固醇肝 X 受体（LXR）和低密度脂蛋白受体（LDLR）基因的表达上调。这些结果表明，植物乳杆菌 AR113 和乳杆菌 pWQH01 可以抑制胆固醇吸收并加速胆固醇转运。综上所述，这些发现表明，过表达胆汁盐水解酶的乳杆菌菌株通过减少胆固醇吸收和增加胆固醇分解代谢对高胆固醇血症具有有益作用。
