Effect Of Theaflavins On Renal Dysfunction And Gut Microbiota Disorder Of Mice In Diabetic Mice

Type 2 Diabetes Mellitus(T2DM)is a serious challenge for all of humanity.As diabetes progresses,it leads to numerous complications,including diabetic nephropathy and gut microbiota disturbance,resulting in a risk of death for patients.Reportedly,theaflavins(TFs)can not only improve diabetic nephropathy,but also have the ability to regulate gut microbiota However,the underlying molecular mechanisms of TFs for the improvement of these complications are not understood.In this study,T2DM mice were treated with different concentrations of TFs by gavage to investigate the effect of TFs on diabetic nephropathy and gut microbiota.The main experiments and results are summarized as follows:(1)To study the effects of TFs on the improvement of blood glucose and lipids in T2DM mice.The main indicators:fasting blood glucose,body weight,food consumption,water consumption,urinary volume,glucose tolerance,insulin homeostasis model,blood lipids,liver oil red O staining and liver function evaluation index were tested.And the TFs were found to significantly reduce fasting glucose,plasma insulin levels and significantly improve oral glucose tolerance,insulin resistance and insulin sensitivity in T2DM mice.At the same time,TFs can effectively reduce total cholesterol,tri-glyceride and low density lipoprotein cholesterol levels,but increase high density lipoprotein cholesterol levels in T2DM mice.In summary,that TFs improve glucose and dyslipidemia by restoring insulin sensitivity in T2DM mice.(2)To study the protective effects of TFs on AGEs-mediated renal injury in T2DM mice,the impaired renal function of each group of mice was tested by observing the biochemical indexes of renal function and HE staining results of T2DM mice.The results showed that TFs significantly reduced 24 h urine protein,urine albumin,serum creatinine,blood urea nitrogen and other renal function indexes,as well as significantly improved the structural damage of the kidney.The results of biochemical experiments indicate that TFs inhibited the formation of AGEs,which reduced the expression of RAGE.Less AGEs,combinded to less RAGE,which inhibited the MAPK/NF-κB signaling pathway in diabetic mice.Eventually,the inflammation and fibrosis were prevented,and the diabetic nephropathy were improved.(3)To study the effects of TFs on the regulation of gut microbiota in T2DM mice,the fecal contents of T2DM mice were analyzed by 16S rRNA high-throughput sequencing.As well as the spearman correlation analysis and functional prediction analysis were performed on diabetes-related indicators and the top 50 genera in total abundance.significantly altered the structure of gut microbiota in diabetic mice,and it was shown that TFs positively shape the intestinal structure.It promotes the growth of beneficial bacteria such as Lachnospiraceae,norank_f_Muribaculaceae,Bifidobacterium,etc,but inhibits the growth of harmful bacteria such as Enterococcus,Colidextribacte and Faecalibaculum increase.In addition,TFs can reshape the metabolic homeostasis of diabetic mice by regulating the participation of gut microbiota in multiple metabolic pathways.