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 This study was a 3x2 prospective randomized trial with a total length of 12-weeks. Male F344BN rats (n= 8-13/group) were randomized to one of three treatments: (i) buffer (Con: n= 25); (ii) a probiotic-Lactobacillus paracasei (LP= 22); or to, (iii) a GMP-Lactobacillus paracasei engineered to express Ang (1-7) (LPA: n= 17). Additionally, these groups were further randomized to a moderate exercise intervention (CONEx : n= 13: LPEx: n=11: LPAEx: n= 8) or to a control group without exercise training (CONSed: n= 12: LPSed: n=11: LPASed: n= 9). The treatment groups were orally gavaged with 2x1011 CFU/kg body weight of probiotics or an equal volume of buffer 3 times per week. Groups randomized to the exercise intervention (CONEx: n= 13: LPEx: n=11: LPAEx: n= 8) performed a treadmill intervention, 5 days per week for 12 weeks.