Supplemental Clostridium butyricumon modulates lipid metabolism of IUGR suckling piglets through reshaping the composition of gut microbiota and bile acid profile

Abstract

Abstract Background Intrauterine growth retardation (IUGR) can cause lipid disorders in infants and have long-term adverse effects on their growth and development. Clostridium butyricumon, emerging as a probiotic, has been reported to attenuate dysfunctions in lipid metabolism with effect. Therefore, the objective of this study was to investigate the effects of C. butyricum supplementation on hepatic lipid disorders in IUGR suckling piglets and to explore its underlying mechanism. Methods sixteen IUGR and eight normal birth weight (NBW) neonatal male piglets were divided into three groups. Besides drinking milk, these neonates were orally gavaged with 10 mL sterile saline (NBW-CON and IUGR-CON groups) or bacterial fluid containing 2 × 108 CFU/kg C. butyricum (IUGR-CB group) once in the morning for 3 to 24 d. Results Piglets with IUGR showed retarded growth performance, impaired hepatic morphology, disordered lipid metabolism, increased abundance of opportunistic pathogens and altered bile acid (BA) profile of ileum and liver. C. butyricum supplementation reshaped the gut microbiota of IUGR piglets and was characterized by a decreased abundance of opportunistic pathogens in the ileum. Among these opportunistic pathogens, Streptococcus and Enterococcus are also bile salt hydrolase (BSH)-producing microbes, and the decrease of them increased the content of conjugated BAs, which could be transported to liver and functioned as signaling molecules to activate liver X receptor α (LXRα) and farnesoid X receptor (FXR). Their activation effectively accelerated the synthesis and oxidation of fatty acids and down-regulated the total cholesterol level by decreasing the synthesis and promoting the efflux of cholesterol. As a result, the final body weight of the IUGR piglets and the morphological structure of their livers improved. Conclusions These results indicate that supplemental 2 × 108 CFU/kg C. butyricum could decrease the abundance of Streptococcus and Enterococcus, which were considered BSH-producing microbes. Their decrease altered the BA profile of the ileum and liver and, as a result, activated the expression of hepatic LXRα and FXR. The activation of these two signalling molecules could effectively normalize lipid metabolism and improve the growth performance of IUGR suckling piglets.