Exercise improves endothelial progenitor cell’s function in mice with Type 2 diabetes via gut microbiota modulation

Abstract

Introduction: Evidence has proved that exercise increases migration and tube formation of rat EPCs. But the mechanism behind the improved function of EPCs by exercise remains unclear. Methods: This study conducted 8-week exercise interventions (aerobic, resistance, or combined) in 6-week-old type 2 diabetic mice, assessing post-exercise glucose, weight, GLP-1, and gut microbiota. Mice with optimal outcomes were selected as fecal donors for microbiota transplantation via gavage. Recipient mice were evaluated for GLP-1, microbiota changes, and endothelial progenitor cell (EPC) proliferation/migration. Results: Exercise altered microbial composition (e.g., increased Prevotellaceae and Ligilactobacillus), while fecal microbiota transplantation(FMT) enriched Akkermansia. Notably, FMT elevated plasma Glucagon-like peptide-1 (GLP-1) levels by 0.92 pmmol/L (P < 0.001) compared to controls, surpassing the modest, non-significant effects of exercise alone. Critically, FMT enhanced EPC’s proliferation (P < 0.007 vs. controls) and migration (P < 0.05), mirroring exercise-induced improvements. While exercise reduced body weight (e.g., 10.58 g in aerobic training (AT), P < 0.001) and blood glucose, FMT amplified these metabolic benefits, lowering glucose by 9.22 mmol/L (P < 0.001). Discussion: Our findings suggest that exercise improves EPC’s function in diabetic mice via gut microbiota modulation, with FMT synergistically enhancing GLP-1 secretion. The identified microbiota (Prevotellaceae, Ligilactobacillus, Akkermansia) may serve as therapeutic targets for T2DM(T2DM) and its cardiovascular complications.