Yue Zhang Xiang Wang Duping DENG ^* Yuanyuan GONG ^* Xuanyi CHEN ^* Juan Li ^* Xiaojuan HONG ^*

• Chengdu University of Traditional Chinese Medicine, Chengdu, China

Objective: To investigate the impact of electroacupuncture (EA) on blood glucose levels, gut microbiota, short-chain fatty acids (SCFAs), and glucagon-like peptide-1 (GLP-1) in a rat model of type 2 diabetes mellitus (T2DM). Methods: Forty Sprague-Dawley (SD) rats were randomly assigned to five groups (n = 8/group) using a random number table: normal control, T2DM model, electroacupuncture (EA), EA + antibiotics (EA+A), and antibiotics (A). EA and EA+A groups received EA treatment at specific acupoints for 30 minutes, six times per week, for four weeks. The water and food consumption, body weight, fasting blood glucose (FBG), and oral glucose tolerance test (OGTT) were monitored. Pancreatic tissue was examined using hematoxylin and eosin (H&E) staining. Fecal microbiota were analyzed by 16S rRNA sequencing, and short-chain fatty acids (SCFAs) were measured by gas chromatography-mass spectrometry. Serum levels of fasting insulin (FINS), glycated hemoglobin (HbA1c), and glucagon-like peptide-1 (GLP-1) were determined by ELISA. Results: EA improved daily water intake, food consumption, and body weight in T2DM rats (P < 0.01). EA reduced FBG, the OGTT, FINS, and homeostasis model assessment of insulin resistance (HOMA-IR) (P < 0.05). ELISA results showed a lower concentration of HbA1c in the EA group (P < 0.05). EA improved the overall morphology and area of pancreatic islets, increased the number of β-cell nuclei, and alleviated β-cell hypertrophy. The abundance of operational taxonomic units (OTUs) in the EA group increased compared to the model group (P < 0.05), and EA upregulated the Shannon, Chao1, and Ace indices (P < 0.05). EA increased the concentrations of acetic acid, butyric acid, and GLP-1 (P < 0.05). Correlation analysis revealed negative associations between Lactobacillaceae and Lactobacillus with FBG. Peptostreptococcaceae and Romboutsia were negatively correlated with HbA1c, while Enterobacteriaceae was positively correlated with OGTT. GLP-1 was positively correlated with acetic acid, butyric acid (R = 0.586, P = 0.000), isovaleric acid, valeric acid, and caproic acid. Antibiotics disrupted the intestinal microbiota structure and weakened the therapeutic effects of EA. Conclusion: EA effectively improved glucose metabolism in T2DM rats. The hypoglycemic effects of EA were associated with the regulation of gut microbiota, SCFAs, and GLP-1.