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

Gaifeng Hou,Liangkai Wei,Wei Peng,Yulong Yin,Rui Li,Xingguo Huang,Yong Yuan

doi:10.3389/fnut.2020.617676

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.

Highlights

Cholesterol is an indispensable fundamental building block for all cell membranes, but long-term high level of blood cholesterol may induce hypercholesterolemia-associated cardiovascular diseases (CVDs), a major contributing factor of adult deaths worldwide [1, 2]
Serum total cholesterol (TC), total bile acids (TBAs), and TG contents in L. delbrueckii–fed pigs were found to be lower than the pigs in the corn–soybean meal diets with either 0% (Con) group (P < 0.05; Figures 2A,C,D)
L. delbrueckii treatment tended to reduce the concentration of serum LDL-C (P = 0.075) and elevate serum high-density lipoprotein cholesterol (HDL-C) (P = 0.093) level (Figure 2A)

Summary

Introduction

Cholesterol is an indispensable fundamental building block for all cell membranes, but long-term high level of blood cholesterol may induce hypercholesterolemia-associated cardiovascular diseases (CVDs), a major contributing factor of adult deaths worldwide [1, 2]. Endogenous synthetic cholesterol accounts for nearly 70%, whereas the remaining 30% amount is mainly derived from animal products [6]. Pork products are rich in cholesterol ranging from 57 mg/100 g in loin to 116 mg/100 g in dewlap [7]. In China, pork is the most popular animal meat, and its production and consumption contribute about 50% of global pork output ranking first in the world [8]. Clarification of underlying mechanisms of cholesterol metabolism in pigs and development of low cholesterol pork products has a promising potential of scientific researches and consumer markets

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Conclusion