The Effects of Tangning Ziyabitusi on Gut Microbiota and T lymphocyte Subsets in Impaired Glucose Regulation Rats

Abstract

Background: Impaired glucose regulation (IGR) represents the prediabetic state and is associated with gut microbiota (GM) dysbiosis and chronic inflammation. Tangning Ziyabitusi Tablet (TZT) is a Chinese Uyghur herbal medicine with preventative and therapeutic effects on diabetes, but its hypoglycemic mechanisms are unclear. Methods: Thirty-six male Wistar rats were divided into the normal diet (ND) and IGR groups. The IGR group was given a high-fat diet (HFD). After the IGR model establishment, the ND group was divided into ND and ND+TZT groups, and the IGR group into IGR and IGR+TZT groups. After 8 weeks of TZT administration, 16S rRNA sequencing and untargeted metabolomics were performed on fecal samples. Mesenteric lymph nodes were also collected, and T lymphocytes separated after rats were sacrificed. Flow cytometry was used to characterize different CD4 + T cell subsets in mesenteric lymph nodes. Finally, we analyzed the correlation between GM and characteristic fecal metabolites. Results: Impaired glucose tolerance and insulin resistance were improved in the IGR+TZT group when compared with the IGR group. Bacterial 16S rRNA sequencing results showed that Sobs and Chao1 indices in the IGR group were significantly decreased, but were increased in the IGR+TZT group. The relative abundance of Bacteroidetes was decreased while the relative abundance of Firmicutes was increased in the IGR group. Adlercreutzia abundance was decreased after TZT administration, while the abundance of Christensenellaceae_R-7_group, norank_f_norank_o_Clostridia_UCG-014, UCG-005, and Eubacterium_nodatum_group was increased in the IGR+TZT group. Lymph node CD4 + T cell proportions in the IGR group were significantly increased, while they were significantly decreased in the IGR+TZT group. Correlation analysis showed that tumor necrosis factor-α, interleukin-6, T helper cells (Th1, Th2, Treg), and insulin had a greater impact on GM community structure. Conclusions: TZT improved glucose tolerance and ameliorated GM dysbiosis in IGR rats. Additionally, TZT significantly modulated CD4 + T cell subset proportions in rat mesenteric lymph nodes and fecal metabolism. Moreover, correlation analysis showed that key microbiota was closely related to IGR indices. Thus, TZT modulated GM composition and immune functions of the intestinal mucosa. We provide useful information for the investigation of active mechanisms and the clinical application of TZT.

The Effect of Theaflavins on the Gut Microbiome and Metabolites in Diabetic Mice

“…Norank_f__Muribaculaceae improve glucose tolerance and insulin resistance in diabetic mice, which may be dependent on their regulation of the SCFA level [77,78]. In this study, consistent with previous studies [79][80][81], the relative abundance of these negatively correlated bacteria significantly decreased in diabetic mice (Table 3) but increased significantly after TFs or metformin intervention (Table 3). These changes in bacteria both positively and negatively correlated with diabetes suggested that TFs could reshape the structure of the gut microbiome, and this may be a strategy to improve diabetes.…”

Natural Sweetener Glycyrrhetinic Acid Monoglucuronide Improves Glucose Homeostasis in Healthy Mice

“…Lactobacillus as beneficial bacteria can alleviate inflammation and plays a positive role in antioxidant and glucose-lowering effects, 28 whereas Adlercreutzia abundance is associated with obesity and insulin resistance in rodents. 29 LEfSe analysis showed that Odoribacter, Ruminiclostridium, and Clostridium_sensu_stricto_1 were more abundant in the GAMG group. These three key genera can produce SCFAs.…”

“…Sucralose increased the Adlercreutzia abundance, which was positively correlated with FBG and the AUC of OGTT, suggesting that Adlercreutzia may be related to the aberrant glycemic response. 29 Additionally, Muribaculaceae_norank, increased in the aspartame group, was negatively correlated with GLP-1 and the gene expression of PYY receptor and GPR43. Aspartame also reduced the butyric acid level.…”

“…The results indicate that GAMG may decrease FBG and enhance insulin sensitivity by increasing Clostridium_sensu_stricto_1 and the related SCFAs. Sucralose increased the Adlercreutzia abundance, which was positively correlated with FBG and the AUC of OGTT, suggesting that Adlercreutzia may be related to the aberrant glycemic response . Additionally, Muribaculaceae_norank , increased in the aspartame group, was negatively correlated with GLP-1 and the gene expression of PYY receptor and GPR43.…”

“…Moreover, Lactobacillus abundance decreased and Adlercreutzia abundance increased in the sucralose group. Lactobacillus as beneficial bacteria can alleviate inflammation and plays a positive role in antioxidant and glucose-lowering effects, whereas Adlercreutzia abundance is associated with obesity and insulin resistance in rodents …”