Effect And Mechanism Of Puerarin On Improving T2DM In Mice Based On Multi-omics Strategy

In the present study,multi-omics techniques was used to determine the effects of Puerarin on gut microbiota,intestinal genes expression and metabolites in mice,and to explore the mechanism of Puerarin on improving T2 DM in mice.The main results are as follows:1.The influence of Puerarin on blood glucose,blood lipids and pancreatic tissues were determined to explore the effect of Puerarin on improving T2 DM in mice.The results showed that Puerarin could significantly reduce the levels of FBG,FINS,TG and LDL,restore the structure of pancreatic islet and repaire injured pancreatic tissues in T2 DM mice.2.The effects of Puerarin on gut microbiota,intestinal genes expression and metabolites in mice were determined by multi-group techniques to explore the mechanism of Puerarin on improving T2 DM in mice:(1)Illumina results showed that compared with DM group,the abundance of Desulfovibrio and Helicobacter decreased,while the abundance of Lactococcus and Bifidobacterium increased.It is suggested that Puerarin could increase the diversity of T2 DM mice gut microbiota,significantly change the species composition of gut microbiota,and reverse the disturbed gut microbiota of T2 DM mice to normal.(2)Illumina results showed that compared with DM group,there were 308 significant different genes in Pue group.Among them,Foxa2 and Haao were significantly up-regulated,while Oga and Srebf1 were significantly down-regulated.It is suggested that Puerarin can improve T2 DM in mice in terms of reducing insulin resistance and enhancing insulin sensitivity by regulating intestinal genes expression.(3)LC-MS results showed that compared with DM group,19 metabolites were identified in Pue group.Among them,the content of 5-hydroxy-L-tryptophan and melatonin significantly increased,while the content of phenylacetylglutamine significantly decreased.It is suggested that Puerarin can improve T2 DM in mice in terms of promoting glucose and lipid metabolism and enhancing insulin sensitivity by affecting the content of metabolites.(4)Multi-omics integrated analysis showed that gut microbiota,significant differential metabolites and significant differential genes were closely related to improving T2 DM of Puerarin.Among them,the increase of 5-hydroxy-L-tryptophan and melatonin was significantly positively correlated with the increase of Haao and other genes,and significantly positively correlated with the increase of unclassified＿Rikenellaceae;the increase of Haao was significantly correlated with the changes of Anaerotruncus and Parabacteroides.It is suggested that Puerarin can improve mice T2 DM by affecting the expression of Haao and other genes,changing the abundance of unclassified＿Rikenellaceae,Parabacteroides,Anaerotruncus and other gut microbiota,and regulating the content of metabolites such as5-hydroxy-L-tryptophan and melatonin.In summary,genes,gut microbiotaare and metabolites are closely related.Puerarin can improve T2 DM in mice by affecting the expression of intestinal genes,changing the abundance of gut microbiota and adjusting the content of metabolites.