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Tangnaikang Alleviates Hyperglycemia and Improves Gut Microbiota in Diabetic Mice.

ABSTRACT: Dysregulation of gut microbiota contributes to the development of type 2 diabetes. To investigate the antidiabetic effect of Tangnaikang and its regulation of gut microbiota in diabetic KKAy mice, a type 2 diabetes mouse model was established by feeding KKAy mice with a high-fat diet (HFD) for 2 weeks. The diabetic KKAy mice were treated with vehicle, Acarbose, or different doses of Tangnaikang once a day for 8 weeks. The fasting plasma glucose (FPG) levels and bodyweights were measured weekly. The fecal and blood samples were collected 8 weeks after treatment. The 16s rRNA sequencing and bioinformatics analysis were conducted to explore the effects of Tangnaikang treatment on the richness, diversity, and relative abundance of gut microbiota. Compared with other treatments, high-dose Tangnaikang (4.68 g/kg) significantly reduced FPG levels while elevating bodyweights in model mice. Compared with saline treatment, different doses of Tangnaikang significantly increased gut microbial species richness and diversity. Linear discriminant analysis effect size identified potential bacterial biomarkers associated with Tangnaikang treatment. Relative abundance analysis revealed that Tangnaikang treatment modulated the abundance of gut bacteria at the class and genus levels, such as Bacilli, Lactobacillus, and Alistipes. The principal component analysis demonstrated that, compared with the samples of the high-dose group, the samples of medium-dose and low-dose groups were closer to those of the model group. Tangnaikang alleviated hyperglycemia and improved the composition and abundance of gut microbiota in diabetic KKAy mice.

SUBMITTER: Zhang L

PROVIDER: S-EPMC8639253 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Introduction The polysaccharides found in Cordyceps cicadae (C. cicadae) have received increasing academic attention owing to their wide variety of therapeutic activities. Methods This study evaluated the hypoglycemic, antioxidant, and anti-inflammatory effects of polysaccharides from C. cicadae (CH-P). In addition, 16s rDNA sequencing and untargeted metabolomics analysis by liquid chromatography-mass spectrometry (LC-MS) were used to estimate the changes and regulatory relationships between gut microbiota and its metabolites. The fecal microbiota transplantation (FMT) was used to verify the therapeutic effects of microbial remodeling. Results The results showed that CH-P treatment displayed hypoglycemic, antioxidant, and anti-inflammatory effects and alleviated tissue damage induced by diabetes. The CH-P treatment significantly reduced the Firmicutes/Bacteroidetes ratio and increased the abundance of Bacteroides, Odoribacter, Alloprevotella, Parabacteroides, Mucispirillum, and significantly decreased the abundance of Helicobacter and Lactobacillus compared to the diabetic group. The alterations in the metabolic pathways were mostly related to amino acid biosynthesis and metabolic pathways (particularly those involving tryptophan) according to the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Correlation analysis showed that Bacteroides, Odoribacter, Alloprevotella, Parabacteroides, and Mucispirillum were positively correlated with indole and its derivatives, such as 5-hydroxyindole-3-acetic acid. Indole intervention significantly improved hyperglycemic symptoms and insulin sensitivity, and increased the secretion of glucagon-like peptide-1 (GLP-1) in diabetic mice. FMT reduced blood glucose levels, improved glucose tolerance, and increased insulin sensitivity in diabetic mice. However, FMT did not significantly improve GLP-1 levels. Discussion This indicates that C. cicadae polysaccharides alleviate hyperglycemia by regulating the production of metabolites other than indole and its derivatives by gut microbiota. This study provides an important reference for the development of novel natural products.

Project description:Background & aimsAccumulating research has addressed the linkage between the changes to gut microbiota structure and type 2 diabetes (T2D). Inulin is one type of soluble dietary fiber that can alleviate T2D. As a prebiotic, inulin cannot be digested by humans, but rather is digested by probiotics. However, whether inulin treatment can benefit the entire gut bacteria community remains unknown. In this study, we evaluated the differences in gut microbiota composition among diabetic, inulin-treated diabetic, normal control, and inulin-treated normal control rats.MethodsA diabetic rat model was generated by a high-fat diet and streptozotocin injections (HF/STZ). Inulin was orally administered to normal and diabetic rats. To determine the composition of the gut microbiota, fecal DNA extraction and 16S rRNA gene 454 pyrosequencing were performed.ResultsWe found that inulin treatment reduced fasting blood glucose levels and alleviated glucose intolerance and blood lipid panels in diabetic rats. Additionally, inulin treatment increased the serum glucagon-like peptide-1 (GLP-1) level, reduced serum IL-6 level, Il6 expression in epididymal adipose tissue, and Pepck, G6pc expression in liver of diabetic rats. Pyrophosphate sequencing of the 16s V3-V4 region demonstrated an elevated proportion of Firmicutes and a reduced abundance of Bacteroidetes at the phylogenetic level in diabetic rats compared to normal control rats. The characteristics of the gut microbiota in control and inulin-treated rats were similar. Inulin treatment can normalize the composition of the gut microbiota in diabetic rats. At the family and genus levels, probiotic bacteria Lactobacillus and short-chain fatty acid (SCFA)-producing bacteria Lachnospiraceae, Phascolarctobacterium, and Bacteroides were found to be significantly more abundant in the inulin-treated diabetic group than in the non-treated diabetic group. In addition, inulin-treated rats had a lower abundance of Desulfovibrio, which produce lipopolysaccharide (LPS). The abundance of Lachnospiraceae was negatively correlated with the blood glucose response after a glucose load.ConclusionIn summary, diabetic rats have different gut microbiota from control rats. Inulin treatment can alleviate gut microbiota dysbiosis in T2D model rats. Moreover, inulin treatment enhanced serum GLP-1 level to suppress IL-6 secretion and production and hepatic gluconeogenesis, resulted in moderation of insulin tolerance.

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Tangnaikang Alleviates Hyperglycemia and Improves Gut Microbiota in Diabetic Mice.

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