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.
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