Multi-omics profiling of the impact of an Angiotensin (1-7)-expressing probiotic combined with exercise training in aged male rats

Angiotensin (1-7) [Ang (1-7)] is an active heptapeptide of the non-canonical arm of the renin-angiotensin system that modulates molecular signaling pathways associated with vascular and cellular inflammation, vasoconstriction, hyperplasia and fibrosis. Pre-clinical evidence suggests that Ang (1-7) is a promising therapeutic target that may ameliorate physical and cognitive decline in prevalent age-related diseases, but its short half-life and low oral bioavailability reduce its applicability in clinical care. This study evaluated a genetically modified probiotic (GMP) that expresses Ang (1-7) as a potential approach to overcome these barriers. We gave this GMP with and without moderate exercise training and evaluated cross-tissue (prefrontal cortex, hippocampus, colon, liver and skeletal muscle) multi-omics responses in aged male rats血管紧张素(1-7)（Angiotensin (1-7)，缩写为Ang (1-7)）是肾素-血管紧张素系统（renin-angiotensin system）非经典分支的活性七肽，可调控与血管及细胞炎症、血管收缩、组织增生及纤维化相关的分子信号通路。临床前研究证据表明，Ang (1-7)是极具潜力的治疗靶点，有望改善高发年龄相关性疾病引发的躯体与认知功能衰退，但因其半衰期短、口服生物利用度低，其在临床诊疗中的应用受到限制。本研究评估了一种可表达Ang (1-7)的基因工程改造益生菌（genetically modified probiotic, GMP），以此作为克服上述局限的潜在方案。我们将该益生菌联合中等强度运动训练或单独给药，对老年雄性大鼠的跨组织（前额叶皮层、海马体、结肠、肝脏及骨骼肌）多组学应答进行了分析检测。