Lactobacillus delbrueckii Interfere With Bile Acid Enterohepatic Circulation to Regulate Cholesterol Metabolism of Growing–Finishing Pigs via Its Bile Salt Hydrolase Activity

Abstract

Microbiota-targeted therapies for hypercholesterolemia get more and more attention and are recognized as an effective strategy for preventing and treating cardiovascular disease. The experiment was conducted to investigate the cholesterol-lowering mechanism of Lactobacillus delbrueckii in a pig model. Twelve barrows (38.70 ± 5.33 kg) were randomly allocated to two groups and fed corn–soybean meal diets with either 0% (Con) or 0.1% Lactobacillus delbrueckii (Con + LD) for 28 days. L. delbrueckii–fed pigs had lower serum contents of total cholesterol (TC), total bile acids (TBAs), and triglyceride, but higher fecal TC and TBA excretion. L. delbrueckii treatment increased ileal Lactobacillus abundance and bile acid (BA) deconjugation and affected serum and hepatic BA composition. Dietary L. delbrueckii downregulated the gene expression of ileal apical sodium-dependent bile acid transporter (ASBT) and ileal bile acid binding protein (IBABP), and hepatic farnesoid X receptor (FXR), fibroblast growth factor (FGF19), and small heterodimer partner (SHP), but upregulated hepatic high-density lipoprotein receptor (HDLR), low-density lipoprotein receptor (LDLR), sterol regulatory element binding protein-2 (SREBP-2), and cholesterol-7α hydroxylase (CYP7A1) expression. Our results provided in vivo evidence that L. delbrueckii promote ileal BA deconjugation with subsequent fecal TC and TBA extraction by modifying ileal microbiota composition and induce hepatic BA neosynthesis via regulating gut–liver FXR–FGF19 axis.

Prevention of High-Fat Diet-Induced Hypercholesterolemia by Lactobacillus reuteri Fn041 Through Promoting Cholesterol and Bile Salt Excretion and Intestinal Mucosal Barrier Functions

“…On the one hand, Fn041 acts on the HF group, not by promoting bacterial colonization, but through inhibiting the reabsorption of bile acids in the ileum and promoting the excretion of cholesterol and bile acids ( 34 ). On the other hand, an increased intestinal bile concentration inhibits the proliferation of Lactobacillus and Bifidobacterium ( 57 ). Therefore, the levels of bile acids produced by the liver and excreted in the feces increase, and the concentration of cholesterol in the serum decreases.…”

Intestinal microbiota of layer hens and its association with egg quality and safety

“…The alteration of BA induced by the intestinal microbes is dependent on the secretion of bile salt hydrolase ( BSH ) to generate unconjugated free BA through deconjugation ( Wahlström et al, 2016 ). Similarly, the BSH produced by Lactobacillus can regulate bile acid enterohepatic circulation to improve cholesterol metabolism, which subsequently contributes to reducing the cholesterol levels in serum and egg yolks ( Choe et al, 2012 ; Hou et al, 2020 ).…”

Gut Microbiota-Derived Metabolites in Colorectal Cancer: The Bad and the Challenges

“…It was found that supplementing with Lactobacillus or Bifidobacterium or both can significantly reduce serum cholesterol. The main mechanism is the use of bile salt hydrolyzing enzymes to decouple the bile, and then precipitation of cholesterol along with the decoupled bile ( 124 , 125 ). Moreover, Our previous studies have found that Clostridium butyricum antagonized against HFD-induced intestinal carcinogenesis and decreased the production of secondary BAs via down-regulating the abundance of Clostridium ( 126 ).…”