The Effects Of Maternal High-salt Diet During Perinatal Period On Their Offspring’s Bile Acid Metabolism

Objective: To explore the effects of high-salt diet during perinatal period on their offspring’s bile acid metabolism and the mechanism of the related gut bacteria changes,we detected the liver bile acids and fecal bile acids in the offspring.Methods: Twenty healthy SPF female C57/BL6 mice and 10 healthy SPF male C57/BL6 mice were balanced with a normal diet at least one week and caged two to one when they were seven-week old.Ten cages of mice were randomly divided into a control(ND)group and a high salt(HS)group.The HS group and the ND group were relatively given high-salt food containing 4% sodium chloride and normal food,sterile water containing 1% sodium chloride and sterile water without sodium chloride since they were mating.This treatment didn’t stop until their offspring weaned.During this period,we observed the food intake and drinking water of pregnant mice and the growth of the offspring after birth.When the offspring weaned,collecting their stool samples and keeping them in the ultra-low temperature refrigerator,and recording their body weight and fasting blood glucose.Sacrifice the weaned mice,we collected their blood,liver,spleen,kidney and intestinal tissues,calculated the organ coefficients,made liver tissue biopsies;by detecting the liver and fecal bile acid and liver bile acid metabolism pathway main gene expression to evaluate the effect on bile acid metabolism in mice;detected the gut bacteria to reflect whether they made sense in the bile acid metabolism system.Results: Compared with the ND offspring,the weight of the HS group decreased significantly(p<0.05).The fasting blood glucose showed a downward trend and the liver and spleen organ coefficients showed a rising trend but all of them had no significant difference.While the kidney organ coefficients showed a significant increase(p <0.05).Compared with the ND offspring,there was no significant difference in liver tissue biopsies,but the bile acid in the liver such as α-Muricholic acid,β-Muricholic acid,λ-Muricholic acid,Ursodeoxycholic acid,Hyodeoxycholic acid,Glycodeoxycholic acid,Glycolithocholic acid decreased significantly(p <0.01).In addition,the expressions of major genes involved in liver bile acid metabolism pathway in the HS group were significantly changed.The expression of rate-limiting enzymes Cyp7a1,FXR and SHP genes were significantly down-regulated(p <0.05),and the expression of Cyp8b1 gene was significantly up-regulated(p <0.05).Compared with the ND offspring,the diversity and composition of gut bacteria of the HS group showed a different trend but had no significant statistical difference.Conclusions: This study found that maternal high-salt dietary interventions during perinatal stage can affect the weight of their offspring and reduce the amount of beneficial bile acids in the liver.This experiment aims to provide a new research direction and theoretical basis for the intervention and treatment of fetal and post-growth metabolic diseases caused by maternal diet during perinatal stage.