The Effects And Mechanisms Of Hyodeoxycholic Acid On Intestinal Epithelial Regeneration And Endocrine Cell Differentiation In Weaned Piglets

The main role of bile acids in the body is to emulsify fat and promote the digestion and absorption of lipids.In recent years,studies have found that bile acids can also bind to farnesoid X receptor(FXR)and G protein-coupled bile acid receptor 1(TGR5)on cell membranes,and activate the corresponding cell signaling pathways,regulating the synthesis,metabolism,and transport-related gene expression of bile acids,glucose,and fatty acids.It has a certain protective effect on the intestinal tract of piglets.However,the effect of deoxycholic acid on the proliferation and differentiation of intestinal epithelial cells is not clear.Therefore,the 21-day-old weaned piglets were used as experimental subjects to study the effects of hyodeoxycholic acid on the intestinal mucosal morphology,digestive enzyme activity and nutrient transport in weaned piglets,and the effects of hyodeoxycholic acid on intestinal epithelial turnover in piglets and their intrinsic mechanisms were further studied.The main findings are as follows: 1.Effects of dietary addition of hyodeoxycholic acid on intestinal epithelial cell renewal and function in weaned pigletsCompared with the control group,the addition of hyodeoxycholic acid significantly decreased the activity of lactase and sucrase in the jejunum(P < 0.05),the alkaline phosphatase activity in the ileum tended to decrease(P < 0.1).The expression of solute translocation(SLC15A1,SLC1A1,SLC5A1,SLC6A19,SLC2A2,SLC7A1)in the jejunum and ileum decreased significantly(P < 0.05).The number of Ki67 positive cells in the duodenal crypt was significantly Increased(P < 0.05),but tended to decrease in the ileal crypt(P = 0.053).The expression level of Bmi1 protein was significantly decreased in the upper part of jejunum villi,but increased significantly in crypt epithelial cells(P < 0.05).The protein expression of β-catenin tended to increase in the upper part of jejunum villi(P = 0.088).2.Effect of dietary addition of hyodeoxycholic acid on intestinal epithelial endocrine cell differentiation in weaned pigletsThe addition of hyodeoxycholic acid significantly reduced the number of chromogranin A-positive cells in jejunum villi and the plasma GLP-2 content(P < 0.05).The mRNA levels of endocrine cell-associated transcription factors Pdx1 and Insm1 in the jejunum were significantly decreased(P < 0.05),and the mRNA levels of Pax4 and Nkx2.2 tended to decrease(P=0.056,P=0.099),the mRNA level of NeuroD1 in the ileum was significantly decreased(P < 0.05).Compared with the control group,the mRNA expression levels of Sst,Gast and GCG in the jejunum of the hyodeoxyc-holic acid group was significantly increased(P < 0.05),and the mRNAexpression of PYY in the ileum tended to decrease(P = 0.055).Adding hyodeoxycholic acid to the diet significantly increased plasma globulin,albumin/globulin(A/G),immunoglobulin A(P < 0.05),and total protein and immunoglobulin G serum levels tended to increase compared to the control group(P = 0.080,P = 0.098).In summary,the addition of 2g/kg hyodeoxycholic acid to the diet can regulate the proliferation and differentiation of intestinal epithelial cells in weaned piglets,and affect the expression of proteins related to Wnt/β-catenin signaling pathway in jejunal epithelial cells.