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Effect of Dapagliflozin on Intestinal Flora in MafA-deficient Mice
Luyao Li1, Shiyao Xu2, Tingting Guo3
1Department of Endocrinology, the Second Hospital of Jilin University, Changchun 130041, Jilin, China.
Objective:
To investigate the effect of dapagliflozin on intestinal microflora in MafA-deficient mice using an animal model of diabetes.
Methods:
Male MafA-deficient mice were administered dapagliflozin (1.0 mg/kg/d) intragastrically for 6 weeks. Mouse body weights and fasting blood glucose levels were measured, and intestinal short-chain fatty acids were measured by gas chromatography. A series of methods was used to analyse the number of primary harmful bacteria in the faeces, and high-throughput sequencing was used to sequence the changes in intestinal flora.
Results:
The weight of the mice decreased after dapagliflozin gavage, and fasting blood glucose was significantly lower than that in the control group (P < 0.001). Acetic acid and butyric acid contents in the intestinal tracts of the mice increased, and the growth of harmful microorganisms, such as Clostridium perfringens, enterococci, Enterobacteriaceae, and intestinal enterococci, was inhibited. Blautia is a species found in the experimental group and was significantly different from the control and blank groups as determined by the LDA score from highthroughput sequencing.
Conclusion:
Dapagliflozin can reduce fasting blood glucose, decrease body weight, increase short-chain fatty acid content, regulate the intestinal microecological balance of the body and promote blood glucose and energy homeostasis.
Insights
Dapagliflozin treatment in diabetic mice lowered blood glucose and body weight. It also improved gut health by increasing beneficial short-chain fatty acids and inhibiting harmful bacteria.
Area of Science:
- Endocrinology
- Microbiology
- Pharmacology
Background:
- Diabetes mellitus is a metabolic disorder characterized by hyperglycemia.
- MafA-deficient mice serve as a model for studying diabetes.
- Intestinal microflora plays a crucial role in host metabolism and health.
Purpose of the Study:
- To investigate the impact of dapagliflozin on the intestinal microflora of MafA-deficient mice.
- To assess the effects of dapagliflozin on metabolic parameters and gut microbial composition in a diabetic mouse model.
Main Methods:
- Male MafA-deficient mice received dapagliflozin (1.0 mg/kg/d) for 6 weeks.
- Measurements included body weight, fasting blood glucose, and intestinal short-chain fatty acids (SCFAs).
- Fecal analysis involved quantifying harmful bacteria and high-throughput sequencing for microbial community profiling.
Main Results:
- Dapagliflozin administration led to a significant reduction in body weight and fasting blood glucose levels.
- Increased levels of acetic acid and butyric acid were observed in the intestinal tracts.
- Inhibition of harmful bacteria (e.g., Clostridium perfringens, Enterobacteriaceae) and significant alterations in microbial composition, including an increase in Blautia, were noted.
Conclusions:
- Dapagliflozin effectively reduces fasting blood glucose and body weight in MafA-deficient mice.
- The drug promotes beneficial gut microbiota changes, increasing SCFA production and regulating the intestinal microecological balance.
- These findings suggest dapagliflozin contributes to improved glucose and energy homeostasis through modulation of the gut microbiome.
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