Experimental Study Of Gynostemma Pentaphyllum Seed Oil Alleviating Type 2 Diabetes In Mice By Modulating Gut Microbiota

Type 2 diabetes mellitus(T2DM)is showing a rising trend worldwide,harming the health of many people.Both the patient and the social medical security system have paid a lot of medical expenses for it.In recent years,more and more literature reports indicate that the intestinal flora also plays an important role in the pathogenesis of diabetes.With the application of intestinal flora sequencing and genome-wide association studies,the role of intestinal flora in the pathogenesis of T2DM has been further confirmed.In view of the important role of intestinal flora in the pathogenesis of diabetes,it has become a research hotspot to adjust the structure of intestinal flora of the body to reduce the symptoms of T2DM through some intervention measures.Our previous studies have shown that Gynostemma pentaphyllum seed oil(GPSO)canimprove insulin resistance in high fat diet mice by regulating glucose and lipid metabolism.The main component of ?-keto acid in GPSO is the most common conjugated linolenic acid(CLnA).CLnA is metabolized in the human body to produce conjugated linoleic acid(CLA).Studies have shown that CLA can regulate the intestinal flora of mice.Therefore,the intestinal flora of the body may be one of the targets of GPSO.There are no reports on the effect of GPSO on the intestinal flora.Here,we hypothesize that the intestinal flora may be another potential target for GPSO for T2DM.In this study,we first demonstrated that GPSO can affect the intestinal flora environment of mice,which optimizes the intestinal flora structure of healthy mice.Then fecal microbiota transplantation(FMT)showed that GPSO can improve the symptoms of diabetes in mice by affecting the intestinal flora.The specific results are as follows:1.Effects of GPSO on body function and intestinal flora of healthy miceEight weeks after GPSO intervention in healthy mice,colonic feces was collected for sequencing when the mice were sacrificed.After the mice were sacrificed,specimens were collected for detection.The results showed that compared with the normal diet group mice,the effects of different doses of GPSO on body weight and main organs were not different.GPSO interfered with the intestinal flora of mice with an increase in the proportion of Firmicutes and a decrease in the proportion of Bacteroides.Eubacterium in the GPSOH group is the dominant flora among the groups.2.GPSO improves the symptoms of T2DM miceT2DM mice animal model was established by high fat diet combined with streptozotocin induction.T2DM mice were treated with GPSO at a dose of 1 mL/kg and 2 mL/kg for 8 weeks.Detection of blood glucose,serum insulin,oral glucose tolerance test,blood lipids,liver and kidney function,ileal inflammatory factors and other indicators found showed that there was no difference in the effect of GPSO at different doses,and all of them significantly improved insulin resistance,glucose and lipid metabolism,and target organ damage in T2DM mice,while also significantly reducing intestinal inflammation and repairing the intestinal barrier.3.GPSO through FMT to improve the symptoms of T2DM miceWe used the method of FMT to transplant the feces of normal mice,T2DM mice and T2DM mice interfered by GPSO to T2DM mice.In the case where the donor mice were all T2DM,the untreated donor feces were transplanted into the recipient T2DM mice(T_T group)which showed more severe weight loss,glucose and lipid metabolism disorders,and liver and kidney damage.After transplanted feces from donor mice with GPSO intervention to recipient T2DM mice(NGH_T group,TGL_T group,and TGH_T group),the above symptoms could be reversed to a certain degree,and no significant difference in three groups.We can speculate that there is no difference between the effects of GPSO administration concentrations of 1 mL/kg and 2 mL/kg.4.Effects of GPSO and GPSO-intervened FMT on intestinal flora of T2DM miceWe performed sequencing analysis of the mice intestinal flora in two parts of the experiment before and after FMT.In the intestinal flora of T2DM mice,the proportion of Firmicutes level decreased and the proportion of Bacteroidetes increased at the phylum level.At the genus level,the proportion of Lactobacillus decreased.The intervention of GPSO could reverse the changes of the above-mentioned flora ratio to a certain extent.Disturbance of intestinal flora in T2DM mice and improvement of intestinal flora in GPSO intervention T2DM mice could be transplanted to recipients T2DM mice by FMT.That is,FMT can transplant the characteristics of mice intestinal flora.At the same time,it further proved the role of intestinal flora imbalance in the progression of T2DM,and also showed that it is feasible to reduce the symptoms of T2DM through GPSO affecting the intestinal flora.Conclusion:The results of this study preliminarily confirmed that GPSO can alleviate T2DM in mice by affecting intestinal flora,which was verified by the FMT method.There is almost no difference between the effects of GPSO at different doses(1 mL/kg and 2 mL/kg).In some respects,the effect of GPSO may be better than metformin(for example,the ratio of Firmicutes and Bacteroidetes,the abundance of Lactobacillus in the intestinal flora of T2DM mice).Therefore,GPSO is expected to play a further role in the clinical treatment of T2DM.