| Objective: To explain the effect of milk source compound probiotics on lipid metabolism in diabetes mice from the perspective of intestinal flora,analyze the correlation between differential bacteria and blood lipid levels,and speculate the possible mechanism related to bile acid metabolism.Methods: Eight db/m mice were used as the normal control group,and 32 db/db mice were divided into model group,positive drug group(metformin),high and low dose groups of milk source compound probiotics.After six weeks of intervention,body weight and fasting blood glucose were measured every week.After six weeks of intervention,mice serum was taken for the determination of blood glucose,blood lipid index and total bile acid.Liver morphology was observed by HE staining.Intestinal contents were taken for high-throughput sequencing of 16 S r RNA,Analyze the effect of milk source compound probiotics on intestinal flora from multiple taxonomy,find out the possible way of improving lipid metabolism in diabetes mice through functional prediction,and detect the expression of liver and intestinal related genes in diabetes mice by RT-PCR.Results:(1)The milk source compound probiotics significantly reduced the fasting blood glucose and glycosylated hemoglobin levels in diabetes mice;Lower the levels of total cholesterol,triglyceride and low-density lipoprotein cholesterol in diabetes mice;Reduce the liver steatosis of diabetes mice,and reduce the number and volume of lipid vacuoles in liver cells;Reduce the level of serum bile acid in diabetes mice;Inhibition of sodium dependent bile acid transporters and organic solute transporters at the tip of the intestine α m RNA expression,inhibition of sodium taurocholate co transporter protein m RNA expression,promotion of bile salt output pump m RNA expression;(2)Change the diversity and structure of intestinal flora in diabetes mice,and the abundance of Corynebacteria,Nocardiaceae,Escherichia Shigella,etc.has changed significantly;The differential genera of low dose composite probiotics are Peptostreptococcaceae and Christensenellaceae＿R-7＿Group and Romboutsia are negatively correlated with TC,TG,and LDL-C,while the differential genus of high-dose probiotics is Escherichia Shigella,which is positively correlated with TC,TG,and LDL-C;Functional prediction showed that primary bile acid biosynthesis,secondary bile acid biosynthesis and other pathways were enriched in the group of compound probiotics,so it was speculated that the effect of dairy compound probiotics on improving lipid metabolism in diabetes mice was related to bile acid metabolism.Conclusion:(1)The milk source compound probiotics can reduce the blood sugar level of diabetes rats,improve blood lipid disorder,and reduce liver steatosis;Reduce the level of serum bile acid in diabetes rats,promote the secretion of bile acid from the liver by up regulating the m RNA expression of bile salt export pump,and down regulate the m RNA expression oforganic solute transport protein α,sodium taurocholate cotransporter and apical sodium dependent bile acid transporter,reduce the transport of bile acid from the liver to the circulatory system,reduce the re-uptake of bile acid by the liver,and thus reduce the reabsorption of bile acid;(2)After the intervention of milk source compound probiotics,the diversity and structure of intestinal flora in diabetes mice changed: the individual differences of intestinal flora structure decreased,and the evolutionary similarity increased;An increase in the abundance of bacterial genera related to the metabolism of short chain fatty acids and bile acids;Low dose compound probiotics differential bacteria belong to Peptostreptococcus,Christensenellaceae＿R-7＿Group and Romboutsia were negatively correlated with TC,TG and LDL-C,while Escherichia Shigella was positively correlated with TC,TG and LDL-C;Functional annotation and prediction show that the improvement of diabetes by milk derived probiotics may be related to functional pathways such as biodegradation and metabolism,bile acid biosynthesis,etc. |
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