Intrauterine growth retardation affects liver bile acid metabolism in growing pigs: effects associated with the changes of colonic bile acid derivatives

Abstract

Background Intrauterine growth retardation (IUGR) is associated with severely impaired nutrient metabolism and intestinal development of pigs. Our previous study found that IUGR altered intestinal microbiota and metabolites in the colon. However, the consequences of IUGR on bile acid metabolism in pigs remained unclear. The present study aimed to investigate the bile acid metabolism in the liver and the profile of bile acid derivatives in the colon of growing pigs with IUGR using bile acid targeted metabolomics. Furthermore, we determined correlations between colonic microbiota composition and metabolites of IUGR and normal birth weight (NBW) pigs at different growth stages that were 7, 21, and 28-day-old, and the average body weight (BW) of 25, 50, and 100 kg of the NBW pigs. Results The results showed that the plasma total bile acid concentration was higher (P < 0.05) at the 25 kg BW stage and tended to increase (P = 0.08) at 28-day-old in IUGR pigs. The hepatic gene expressions related to bile acid synthesis (CYP7A1, CYP27A1, and NTCP) were up-regulated (P < 0.05), and the genes related to glucose and lipid metabolism (ATGL, HSL, and PC) were down-regulated (P < 0.05) at the 25 kg BW stage in IUGR pigs when compared with the NBW group. Targeted metabolomics analysis showed that 29 bile acids and related compounds were detected in the colon of pigs. The colonic concentrations of dehydrolithocholic acid and apocholic acid were increased (P < 0.05), while isodeoxycholic acid and 6,7-diketolithocholic acid were decreased (P < 0.05) in IUGR pigs, when compared with the NBW pigs at the 25 kg BW stage. Moreover, Spearman’s correlation analysis revealed that colonic Unclassified_[Mogibacteriaceae], Lachnospira, and Slackia abundances were negatively correlated (P < 0.05) with dehydrolithocholic acid, as well as the Unclassified_Clostridiaceae abundance with 6,7-diketolithocholic acid at the 25 kg BW stage. Conclusions These findings suggest that IUGR could affect bile acid and glucolipid metabolism in growing pigs, especially at the 25 kg BW stage, these effects being paralleled by a modification of bile acid derivatives concentrations in the colonic content. The plausible links between these modified parameters are discussed.

Metabolic and fecal microbial changes in adult fetal growth restricted mice

“…Akkermansia improves intestinal barrier function 69 known to be altered in FGR models; 70 – 72 increases short-chain fatty acid production, 67 diminished in FGR pigs; 61 and facilitates bile acid metabolism, 62 altered in FGR piglets. 73 We also report positive correlation of lean mass with Akkermansia abundance in FGR males. Skeletal muscle mass is a major driver of insulin sensitivity 74 and known to be reduced across the lifespan in humans with FGR.…”

Gut microbiota and metabolite variations in a migraine mouse model

“…Fusimonas intestini , a commensal species of the Lachnospiraceae family, highly colonizes obese and hyperglycemic humans and mice, producing long-chain fatty acids, such as elaidic acid, thus promoting diet-induced obesity ( Takeuchi et al., 2023 ). However, another study reported that the abundances of unclassified Mogibacteriaceae, Lachnospira , and Slackia exhibited significant negative correlations with dehydrolithocholic acid ( Liu et al., 2022 ).…”

Bile Acid Metabolic Profiles and Their Correlation with Intestinal Epithelial Cell Proliferation and Barrier Integrity in Suckling Piglets

“…For instance, key enzymes such as bile salt hydrolases, which can promote the conversion of conjugated bile acids to free bile acids, have been found in almost all bacterial phyla and archaeal systems [25]. In the intestines of growth-retarded piglets, the abundance of Bacteroidia was positively correlated with the contents of glycine-conjugated bile acids (such as GHCA), while the abundance of Lactobacillus was negatively correlated with GHCA and positively correlated with HCA levels [15]. Additionally, certain bacterial groups, such as Clostridium scindens, Clostridium hylemonae, Clostridium perfringens, and Peptostreptococcus hiranonis, have been found to regulate the epimerization of bile acids.…”

“…Similarly, studies have reported that hyodeoxycholic acid (HDCA) inhibits the proliferation and differentiation of IPEC-J2 cells and intestinal organoids [13,14]. Similarly, compared to normal piglets, the levels of LCA and dehydrocholic acid (DHCA) in the intestines of IUGR piglets were significantly increased, which may be the reason for the growth inhibition of IUGR piglets [15]. Due to the diverse range of BA types, the regulatory effects of different BAs on the intestine may be species-or tissue-specific or related to the physiological or pathological state of the body.…”