Changes Of Bile Acids,Intestinal Flora And Intestinal Transit Function In Parenteral Nutrition Associated Liver Disease

Objectives To investigate the changes of bile acids,intestinal flora and intestinal transit function in parenteral nutrition-associated liver disease.Methods Male 4-week-old rats received either PN or saline via the right jugular vein for 7 days.Liver injury was evaluated by serum TBA,ALT,AST,TBI,DBI and histology.The composition of serum bile acid,cecal microbiome,intestinal transit as well as the expression of TGR5 in ileum were measured.The study was divided into three parts.1.Establish parenteral nutrition-associated liver disease(PNALD)rat model and measure the composition of serum bile acid.2.Analyze the cecal microbiome of the PNALD rat model.3.Measure the intestinal motility and expression of TGR5 in the ileum of the PNALD rat model.Results 1.The composition of serum bile acid changed in the PNALD rat model.Hepatic steatosis was observed in TPN group.The composition of serum bile acid was significantly different between two groups.A higher ratio of secondary bile acid to primary bile acid was found in TPN group.2.Composition and function of cecal microbiome changed in the PNALD rat model.? diversity in TPN group decreased.PCoA and adonis analysis showed a significant difference between two groups.The abundance of pathway ‘Secondary bile acid biosynthesis' was higher in TPN group.The percentage of bacteria expressing 7alpha-HSDH in general increased.The abundance of KOs and enzymes associated with BSH was higher.3.Altered ileum motility accompanied with a decreased expression of TGR5 After administration of a charcoal meal test 15 min and 30 min,the distance traveled by the front of the charcoal meal/total length of intestinal was similar between two groups,while the intestinal transit was accelerated at 60 min after charcoal meal administration in TPN group.The expression of the TGR5 protein in ileum decreased.Conclusions Hepatic steatosis was observed after PN for 7 days.Though serum TBA concentration was unchanged,the composition was significantly different,consistent with the functional changes of the cecal microbiome.Ileum transit is accelerated accompanied with a decreased expression of TGR5.Alteration in ileum motility may be associated with the decreased expression of TGR5 in the ileum.