High dietary salt consumption in advanced age influences gut microbiota composition, metabolic flexibility, and cardiovascular response in exercise‐resistant rat model
Authors: Zhang Youjie , Spegele Adam Christopher , Doty Tyler Hugle , Koch Lauren Gerard 
Published: June 2021

AimsPopulations of older (>age 65) adults are among the most varied for predicting beneficial outcomes to exercise and most vulnerable to environmental stressors (i.e., dietary change). Growing evidence suggests that inter‐individual variation in response to exercise plays a role in sustaining metabolic fitness and maintenance of healthspan. Given the importance of exercise capacity in predicting complex disease risk, we hypothesized that exercise‐resistant individuals with low response to exercise training are more vulnerable to the ill‐effects of dietary change and gut microbiota perturbation during aging when compared to exercise‐sensitive individuals with high response to exercise training.MethodsTo test our hypothesis, we fed 22–23‐months old male high response trainer (HRT) and low response trainer (LRT) rats with a high salt diet (2% NaCl, HSD) for 32 days. HRT and LRT rat models were developed by selectively breeding for low and high gain in running distance after 8 weeks of standardized treadmill exercise. Fecal microbial communities of HRT and LRT rats before and after HSD were profiled using 16S rRNA sequences. To test the effects of high dietary salt consumption on metabolic flexibility and cardiovascular risks, whole body metabolism was measured by indirect calorimetry (n = 10 per group, generation 24 of breeding selection). Cardiovascular response (e.g. blood pressure, heart rate) to HSD was monitored weekly using radiotelemetry (n = 11–12 per group, generation 23 of breeding selection) over the span of 24 hours.Results and ConclusionWe observed significant change in the composition of gut microbiota before and after HSD (i.e., increased Firmicutes/Bacteroidetes ratio). HSD consumption significantly altered energy metabolism in LRT rats as indicated by progressive decreases in both RER and glucose oxidation, and increases in fat oxidation. Interestingly, high salt intake appeared to decrease drinking and food consumption in LRT animals without any change in body weight. LRT rats also exhibited significantly decreased heart rate after HSD, especially during dark phase. However, we did not observe a significant increase in blood pressure during the course of the study in either LRT or HRT. Overall, our data suggests that high dietary salt consumption induces symbiosis of gut microbiota, reprioritizes energy metabolism, and triggers cardiovascular response in aged, exercise‐resistant rats over exercise‐sensitive rats, which may be associated with a decline of healthspan in exercise‐resistant individuals. Our study demonstrates HRT and LRT rats are a valuable contrasting animal model system for the study on the impacts of lifestyles and aging on metabolic fitness and cardiovascular risks.Support or Funding InformationResearch support: NIH Office of Research Infrastructure Programs grant P40OD021331.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.