Table 6_Exercise improves endothelial progenitor cell’s function in mice with Type 2 diabetes via gut microbiota modulation.docx

IntroductionEvidence 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.
MethodsThis 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.
ResultsExercise 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).
DiscussionOur 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.

引言
已有研究证实，运动可促进大鼠内皮祖细胞（Endothelial Progenitor Cells, EPCs）的迁移及管腔形成能力，但运动改善EPC功能的具体分子机制仍未明确。

研究方法
本研究对6周龄的2型糖尿病小鼠实施为期8周的运动干预（包括有氧运动、抗阻运动或联合运动），并检测运动后小鼠的血糖、体重、胰高血糖素样肽-1（Glucagon-like Peptide-1, GLP-1）水平与肠道菌群组成。选取干预效果最优的小鼠作为粪便供体，通过灌胃法进行粪便菌群移植（Fecal Microbiota Transplantation, FMT）。随后对受体小鼠的GLP-1水平、菌群结构变化及内皮祖细胞（EPC）的增殖与迁移能力进行评估。

研究结果
运动可改变小鼠肠道菌群结构（例如，提升普雷沃氏菌科（Prevotellaceae）与利格乳杆菌属（Ligilactobacillus）的丰度），而粪便菌群移植（FMT）则可富集阿克曼菌属（Akkermansia）。值得注意的是，与对照组相比，FMT可使血浆GLP-1水平升高0.92皮摩尔每升（P < 0.001），其效果优于单纯运动带来的微弱且无统计学意义的变化。至关重要的是，FMT可增强EPC的增殖能力（与对照组相比，P < 0.007）与迁移能力（P < 0.05），这与运动诱导的功能改善效果一致。尽管运动可降低小鼠体重（如有氧运动训练（Aerobic Training, AT）组小鼠体重降低10.58g，P < 0.001）与血糖水平，但FMT进一步强化了这些代谢获益，使血糖降低9.22mmol/L（P < 0.001）。

讨论
本研究结果表明，运动可通过调控肠道菌群改善糖尿病小鼠的EPC功能，而FMT可协同增强GLP-1的分泌。本次研究鉴定出的普雷沃氏菌科、利格乳杆菌属与阿克曼菌属，或可作为2型糖尿病（Type 2 Diabetes Mellitus, T2DM）及其心血管并发症的治疗靶点。