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.

Early colonization in the gut by probiotics influences the progressive development and maturity of antioxidant and immune system functionality in the future. This study investigated the impact of orally administrated Lactobacillus delbrueckii (LAB) during the suckling phase on future antioxidant and immune responses of the host, using a piglet model. One hundred neonatal piglets received saline (CON) or LAB at the amounts of 1, 2, 3, and 4 mL at 1, 3, 7, and 14 d of age, respectively. The piglets were weaned at the age of 21 d and fed until the age of 49 d. Serum, liver, and intestinal samples were obtained at 21, 28, and 49 d of age. The results showed that LAB tended to decrease serum 8-hydroxy-2-deoxyguanosine concentration and decreased the concentration of serum and hepatic malondialdehyde, but increased the activity of hepatic glutathione peroxidase on days 21, 28, and 49. The concentrations of secretory immunoglobulin A and some inflammatory cytokines and chemokines were increased (P<0.05) in the intestinal mucosa of LAB-treated piglets on days 21, 28, and 49 compared to that of CON piglets. Likewise, protein expression of cyclooxygenase 2 and inducible nitric oxide synthase in the intestine of LAB-treated piglets was increased (P<0.05) during the whole period. These results indicate that administration of LAB to the suckling piglet could improve antioxidant capacity and stimulate intestinal immune response, and these long-lasting effects are also observed up to 4 weeks after weaning. A proper utilization of LAB to neonates would be beneficial to human and animal’s future health.

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